Chronic Kidney Disease - Role of Physician in
The Management And Prevention
Dr (Prof) Sham Sunder
Dr Venkataramanan K *
Head of department
DM Nephrology*
Department of Nephrology
Dr Ram Manohar Lohia
Hospital and PGIMER
New Delhi
Vol. 11, Issue 4, October 2012
Dr (Prof) Sham Sunder and Dr Venkataramanan K
Chronic kidney diseases have become a
major cause of global morbidity and
mortality both developed and in
developing countries. CKD is a problem
of epidemic proportions in India, and
with an increasing diabetes,
hypertension burden, and growing
elderly population. Under recognition of
earlier stages of CKD and of risk factors
for CKD, may partially explain the rising
prevalence of treated ESRD. Increasing
evidence accumulated in the past
decades indicates that earlier stages of
CKD can be detected through laboratory
testing, and that therapeutic
interventions implemented early in the
course of CKD are effective in slowing or
preventing the progression toward ESRD
and its associated complications
Screening, early diagnosis and early
referral of high risk patient by physicians
and subspecialties is the key to reduce
CKD burden.
Introduction
In 21st century CKD is global pandemic,
evolved as major public health issue. CKD
is major silent killer and is highly under
diagnosed and under treated. The
number of cases of end-stage renal
disease (ESRD) in India is increasing due
to risk factors such as diabetes1. It is
estimated that about 500 millions are
known patient of CKD globally.
CKD is irreversible progressive disease
ultimately leading to ESRD and also
premature CAD. Prevalence and
incidence of CKD is increasing fast. Every
third diabetic and every fifth
hypertensive is case of CKD. Mean age
of patient entering ESRD in our country is
42 years as compare to 62 years in
Western countries.
CKD is a disease which is highly under
diagnosed and under treated.
Establishing preventive program is
required to reduce burden of CKD.
Since, CKD is one of the most
devastating, expensive disease and not
an uncommon life-threatening condition
requiring care by nephrologists, is a
common condition with a range of
severity meriting attention by general
physician, and demanding strategies for
prevention, early detection, and
management.
Definition of CKD
CKD is defined by the presence of
kidney damage or decreased kidney
function for three or more months,
irrespective of the cause. The persistence
of the damage or decreased function for
at least three months is necessary to
distinguish CKD from acute kidney
disease. Kidney damage refers to
pathologic abnormalities, whether
established via renal biopsy or imaging
studies, or inferred from markers such as
urinary sediment abnormalities or
increased rates of urinary albumin
excretion.
Table 1. Formula for EGFR calculator
1. Equation from the Modification of
Diet in Renal Disease study*
Estimated GFR (mL/min per 1.73 m2) =
1.86 x (PCr)–1.154 x (age)–0. 203
Multiply by 0.742 for women,Multiply
by 1.21 for African Americans
2. Cockcroft-Gault equation
Estimated creatinine clearance
(mL/min)
= (140–age) x body weight (kg)/72 x
PCr (mg/dL)
Multiply by 0.85 for women
Table 2. Revised CKD classification based upon Decreased kidney function refers to a decreased
GFR and albuminuria.2 glomerular filtration rate (GFR), which is usually estimated
(eGFR) using Serum Creatinine Concentration (PCr), Age,
GFR stages GFR
(mL/min/1.73 m2) Sex, Race, and Body Weight.
G1 >90 Normal or high
G2 60-89 Mildly decreased Prevention of Chronic Kidney Disease
Prevention of CKD mainly involves the Screening for
G3a 45-59 Mildly to moderately
decreased chronic kidney disease and preventing or slowing the
G3b 30-44 Moderately to severely progression of renal disease.
decreased
G4 15-29 Severely decreased Screening for Chronic Kidney Disease - The presence of
G5 <15 Kidney failure (add D if the following risk factors for CKD should provoke formal
treated by dialysis) testing for CKD:
Albuminuria AER (mg/d) Terms · History of diabetes, cardiovascular disease,
stages hypertension, hyperlipidemia, obesity, metabolic
A1 <30 Normal to high normal syndrome, smoking, HIV or hepatitis C virus infection,
(may be subdivided for and malignancy
risk prediction)
· Family history of kidney disease, treatment with
A2 30-300 High (predict
microalbuminuria) potentially nephrotoxic drugs, and all patients over
age 60 years.
A3 >300 Very high (may be
subdivided into nephrotic
and non-nephrotic for NKF-K/DOQI guidelines proposed an algorithm for the
differential diagnosis, evaluation of proteinuria Fig:1
management and risk
prediction)

Evaluation for proteinuria

Not at ­ risk at ­ risk

Standard dipstick Albumin specific dipstick

>1+ Negative / trace Negative positive

Total protein / creatinine ratio Albumin / creatinine ratio

>200 mg/g <200mg/g <30 mg/g >30mg/g

Recheck at periodic health evaluation

Diagnosis evaluation

Treatment Consultation
Fig:1

Vol. 11, Issue 4, October 2012

Methods of screening - All patients who have risk factors
for CKD should be screened with both a urine test for
albumin in a first morning or a random "spot" urine sample
(Fig 1) and a blood test for creatinine to estimate GFR.
Slowing the Rate of Progression of Renal Disease
Therapy to slow the rate of progression in patients with
chronic kidney disease (CKD) includes the treatment of the
underlying disease, attaining the blood pressure goal
and, in patients with proteinuric disease, attaining the
proteinuria goal.
1) Control of Blood Pressure
Treating hypertension can both slow the progression of
proteinuric CKD and reduce the rate of cardiovascular
complications. The desired degree of blood pressure
control can usually be safely achieved with combined
therapy which usually begins with an ACE inhibitor or
angiotensin II receptor blocker (by monitoring
hyperkalemia) and a diuretic.
A loop diuretic is recommended for the treatment of
hypertension and edema in patients with chronic kidney
disease. Thiaziade diuretics are ineffective when GFR is
less than 50 ml/min.
Management of blood pressure in CKD, the goal blood
pressure depends upon the degree of proteinuria:
· In patients with proteinuric CKD (500 to 1000
mg/day or more), the blood pressure should be
lowered to less than 130/80 mmHg.
· In patients with nonproteinuric CKD (less than 500mg
/day), the blood pressure should be lowered to less
than 140/90 mmHg in all patients, and to less than
130 to 135 mmHg systolic if it can be achieved
without producing significant side effects.
2. Control of Blood Glucose:
Diabetic nephropathy is now the leading cause of CKD
requiring renal replacement therapy (>40%). Excellent
glycemic control reduces the risk of kidney disease and its
progression in both type 1 and type 2 diabetes mellitus. It
is recommended that plasma values for preprandial
glucose be kept in the 90–130 mg/dL range and
hemoglobin A1C should be < 7%. Renal degradation of
administered insulin will decline, so that less insulin may be
required for glycemic control drugs.
3. Control of proteinuria:
Increased urinary protein excretion is the earliest clinical
finding of nephropathy.
The normal rate of albumin excretion is less than 20
mg/day (15 mcg/min); persistent values between 30 and
300 mg/day (20 to 200 mcg/min) in a patient with
diabetes is called microalbuminuria and above 300
mg/day (200 mcg/min) are considered to represent
overt diabetic nephropathy.

Table 3: Recommendations for the use of oral anti-diabetic agents in patients with diabetes and renal disease

Class of drug Safety profile in renal disease Remarks

1st generation sulphonylureas Unsafe Risk of prolonged hypoglycaemia

2nd generation sulphonylureas Glipizide safe Glipizide is preferred. Others to be avoided.

Rest unsafe Risk of hypoglycaemiaa

a-Glucosidase inhibitors Unsafe Possible hepatotoxicity

Biguanides Unsafe Risk of lactic acidosis

Thiazolidinediones Safe Volume retention may occur especially with insulin

Meglitinides Repaglinide safe Short half-life and minimal renal excretion of

Nateglinide not repaglinide Significant risk of hypoglycemia with
Completely safe nateglinide

DPP-4 inhibitors Relatively safe Dose adjustment needed for moderate to severe renal
disease

Amylin analogs Safe No dose adjustment required for moderate to severe

renal disease.
No data available for ESRD and dialysis patients.

Vol. 11, Issue 4, October 2012

Establishing the diagnosis of microalbuminuria requires
the demonstration of a persistent (at least two abnormal
tests) elevation in albumin excretion. Screening for
microalbuminuria can be deferred for five years after the
onset of disease in patients with type 1 diabetes. It should
begin at diagnosis in patients with type 2 diabetes
because many have had diabetes for several years
before diagnosis.
Antihypertensive treatment reduces albuminuria and
diminishes its progression even in normotensive diabetic
patients. In patients with diabetes who have
microalbuminuria or overt nephropathy, ACE inhibitors or
angiotensin receptor blocker (ARB), both lower urinary
protein excretion and slow the rate of disease
progression..
Strong evidence favors the use of an angiotensin
converting enzyme (ACE) inhibitor or ARB as first-line
therapy to lower blood pressure in patients with
proteinuric /Diabetic CKD because these drugs slow the
rate of progression of CKD compared with other
antihypertensive. These salutary effects are mediated by
reducing intraglomerular pressure and inhibition of
angiotensin-driven sclerosing pathways, in part through
inhibition of TGF-beta-mediated pathways.
4. Lipid lowering
Elevation in lipid levels also may contribute to the
development of glomerulosclerosis in chronic kidney
disease. Plasma cholesterol concentration above 220
mg/dL (5.7 mmol/L) was an important risk factor for
progressive renal disease. Lipid lowering (at least with
statins) may slow the rate of progression of chronic kidney
disease.
5. Dietary modification and Protein restriction
The optimal level of protein intake has also not been
determined but it may be reasonable to restrict intake to
0.8 to 1.0 g/kg per day of high biologic value protein,
with the lower value used in patients with progressive CKD
(stage II & stage III). Some recommend even lower levels,
such as 0.6 to 0.75 g/kg per day of high value protein in
CKD(stage IV &stage V)patients with close supervision
and dietary counseling3. There is some evidence of Low
Protein Diet Supplemented Keto-/Amino Acid in
Preventing the Progression of CKD.
6. Avoidance of nephrotoxic drugs
The administration of drugs or diagnostic agents that
Vol. 11, Issue 4, October 2012
adversely affect renal function are a frequent cause of
worsening renal function. Among patients with chronic
kidney disease, common offenders include
aminoglycoside antibiotics (particularly with unadjusted
doses), nonsteroidal antiinflammatory drugs, and
radiographic contrast material should be avoided or used
according to strict guidelines when medically necessary.
7. Smoking cessation
Smoking stoppage is associated with a slower rate of
progression of CKD,4. In an increasing number of studies,
smoking also appears to correlate with an enhanced risk
of developing kidney disease (primarily nephrosclerosis)
as well as increasing the rate of progression among those
with existing CKD5 .
Treatment of Chronic Kidney Disease
Treatment of CKD mainly comprises of treatment of the
complications of renal dysfunction and Identification and
adequate preparation of the patient in whom renal
replacement therapy will be required
Treatment of the complications of renal dysfunction - A
wide range of disorders may develop as a consequence
of the loss of renal function.
Volume overload - Sodium and intravascular volume
balance are usually maintained via homeostatic
mechanisms until the GFR falls below 10 to 15 mL/min.
Patients with chronic kidney disease and volume overload
generally respond to the combination of dietary sodium
restriction and diuretic therapy.
Hyperkalemia - In CKD,hyperkalemia may be
precipitated by increased dietary potassium intake,
protein catabolism, hemolysis, hemorrhage, transfusion of
stored red blood cells, and metabolic acidosis associated
with decreased urine output. In addition, a host of
medications such as angiotensin-converting enzyme (ACE)
inhibitors, angiotensin receptor blockers (ARBs), and
spironolactone and other potassium-sparing diuretics such
as amiloride, eplerenone, and triamterene can inhibit
renal potassium excretion.
Metabolic acidosis - There is an increasing tendency to
retain hydrogen ions among patients with chronic kidney
disease 6, 7. There are three major reasons why
treatment of the acidemia may be desirable in patients
with chronic kidney disease.
1. Bicarbonate supplementation may slow the
progression of chronic kidney disease.
2. Bone buffering of some of the excess hydrogen ions is
associated with the release of calcium and phosphate
from bone, which can worsen the bone disease.
3. Uremic acidosis can increase skeletal muscle
breakdown and diminish albumin synthesis, leading to
loss of lean body mass and muscle weakness.
4. We recommend alkali therapy to maintain the serum
bicarbonate concentration above 23 meq/L8, 9. If
alkali is given, sodium bicarbonate (in a daily dose of
0.5 to 1 meq/kg per day) is the agent of choice.
Sodium citrate (citrate is rapidly metabolized to
bicarbonate) may be used in patients who are unable
to tolerate sodium bicarbonate,
Hyperphosphatemia - A tendency toward phosphate
retention begins early in renal disease, due to the
reduction in the filtered phosphate load and the
hypersecretion of parathyroid hormone (PTH) is initially
a p p ro p r i a t e, s i n c e P T H c a n c o r r e c t b o t h
hyperphosphatemia and hypocalcemia. As a result,
phosphate balance and a normal serum phosphate
concentration are generally maintained in patients with a
GFR of greater than 30 mL/min 10. The price paid is
secondary hyperparathyroidism and the development of
renal osteodystrophy.
Once the GFR falls below 25 to 30 mL/min, the addition of
oral phosphate binders are usually required to prevent
hyperphosphatemia 11
One of the preferred agents to bind intestinal phosphate
is calcium salts, of which the most widely used are calcium
carbonate and calcium acetate. Phosphate binders are
most effective if taken with meals to bind dietary
phosphate.Hypercalcemia is a common complication of
this regimen.
Table 4: Recommended Ranges for Selected Biochemical Parameters According to Stage of Chronic Kidney Disease12
CKD Stage GFR Range Phosphorus
(mL/min/1.73 m2) (mg/dL)
30 – 59 2.7 – 4.6
15 – 29 2.7 – 4.6
<15, dialysis 3.5 – 5.5
Sevelamer carbonate controls the serum phosphate
concentration without inducing hypercalcemia. Lanthanum
carbonate when chewed also has significant phosphate
binding properties. Aluminum hydroxide, Magnesium-
containing antacids, Calcium citrate are other phosphate
binders should be avoided.
Mineral bone disease - The principal types of renal bone
disease include osteitis fibrosa, osteomalacia, and
adynamic bone disease.
Osteitis fibrosa results from secondary
hyperparathyroidism. Prevention and/or treatment of
osteitis fibrosis in patients with predialysis chronic kidney
disease are primarily based upon dietary phosphate
restriction, the administration of oral phosphate binders,
and the administration of calcitriol (or vitamin D analogs)
to directly suppress the secretion of parathyroid hormone.
Anemia - A normocytic, normochromic anemia is
observed as early as stage 3 CKD and is almost universal
by stage 4. The primary cause in patients with CKD is
insufficient production of erythropoietin (EPO) by the
diseased kidneys. Additional factors include iron
deficiency, acute and chronic inflammation with impaired
iron utilization ("anemia of chronic disease"), severe
hyperparathyroidism with consequent bone marrow
fibrosis, shortened red cell survival in the uremic
environment, Folate or vitamin B12 deficiency and
Hemoglobinopathy. For CKD patients, initiate ESAs when
Hgb levels are less than 10 g/dL and try to maintain goal
Hgb levels between 11 and 12 g/dL.
However, the goals of ESA treatment are patient-specific.
Adequate bone marrow iron stores should be available
before treatment with EPO is initiated. The availability of
recombinant human EPO has obviated the need for
Calcium (corrected) Ca × P Intact PTH
(mg/dL) (pg/mL)
8.4 – 10.2 35 – 70
8.4 – 10.2 70 – 110
8.4 – 9.5 <55 150 – 300
regular blood transfusions in severely anemic CKD
patients. Frequent blood transfusions in dialysis patients
also lead to the development of allo-antibodies that could
sensitize the patient to donor kidney antigens and make
renal transplantation more problematic.
Treatment of Complications of ESRD - Once the patient
has reached the stage of near end-stage renal disease
(GFR less than 15 mL/min), signs and symptoms related to
uremia begin to occur, such as malnutrition, anorexia,
nausea, vomiting, fatigue, sexual dysfunction, platelet
dysfunction, pericarditis, and neuropathy.
Malnutrition - Malnutrition is common in patients with
advanced chronic renal disease because of a lower food
intake (principally due to anorexia), decreased intestinal
absorption and digestion, and metabolic acidosis 15.
Overall, the diet of most patients with chronic kidney
disease in hemodialysis should provide approximately 30
to 35 kcal/kg per day and protein about 1.2 gm/kg per
day16.
Uremic bleeding - An increased tendency to bleeding is
present in both acute and chronic kidney disease,due
primarily to impaired platelet function. A number of
different modalities can be used in this setting, including
the correction of anemia, the administration of
desmopressin (dDAVP), cryoprecipitate, estrogen, and the
initiation of dialysis.
Referral to nephrologists - Patients with CKD should be
referred to a nephrologist early in the course of their
Table 5. Criteria for nephrology referral
· Urine albumin-to-creatinine ratio (ACR) >300 mg/g
(34 mg/mmol)
· Hematuria not secondary to urological conditions
· Inability to identify a presumed cause of CKD
· eGFR decline of more than 30 percent in fewer than
four months without an obvious explanation
· Difficult to manage complications such as anemia
requiring erythropoietin therapy, and abnormalities
of bone and mineral metabolism requiring phosphorus
binders or vitamin D preparations
· Serum potassium greater than 5.5 meq/L, Difficult to
manage drug complications
· Patients under the age of 18 years, Resistant
hypertension.
disease, preferably before the plasma creatinine
concentration exceeds 1.2 and 1.5 mg/dL in women and
men, respectively, or the eGFR is less than 60 mL/min per
1.73 m2. Lower costs and/or decreased morbidity and
mortality may be associated with early referral and care
by subspecialists 17-19.
Nephrologists can assist primary care physicians and
other specialists in the diagnosis and care of patients at all
stages of CKD. Because patients with CKD are at risk for a
diverse set of adverse outcomes (not just kidney failure),
referral to other appropriate specialists (eg, cardiologists
for those with complex CVD) should also be considered.
Preparation for and initiation of renal replacement
therapy - It is important to identify patients who may
eventually require renal replacement therapy since
adequate preparation can decrease morbidity and
perhaps mortality. Early identification enables dialysis to
be initiated at the optimal time with a functioning chronic
access and may also permit the recruitment and
evaluation of family members for the placement of a
renal allograft prior to the need for dialysis.
Indications for renal replacement therapy - We suggest
that, among patients with progressive CKD, clinicians must
be vigilant for the presence of symptoms and/or signs of
uremia and patients should also be fully informed of any
symptoms of uremia to be able to contact their physicians
Indications include :
· Pericarditis or pleuritis (urgent indication), Progressive
uremic encephalopathy or neuropathy, with signs such
as confusion, asterixis, myoclonus, wrist or foot drop,
or, in severe, cases, seizures (urgent indication)
· A clinically significant bleeding diathesis attributable
to uremia (urgent indication)
· Fluid overload refractory to diuretics
· Hypertension poorly responsive to antihypertensive
medications
· Persistent metabolic disturbances that are refractory
to medical therapy. These include hyperkalemia,
metabolic acidosis, hypercalcemia, hypocalcemia,
and hyperphosphatemia.
· Persistent nausea and vomiting
· Evidence of malnutrition. Relative indications for the
initiation of dialysis include decreased attentiveness
 and cognitive tasking, depression, persistent pruritus
or the restless leg syndrome.
Choice of renal replacement therapy - Once it is
determined that renal replacement therapy will
eventually be required, the patient should be counseled to
consider the advantages and disadvantages of
hemodialysis, peritoneal dialysis (continuous or
intermittent modalities), and renal transplantation (living
or deceased donor).
Hemodialysis requires a chronic vascular access to the
bloodstream to permit dialysis to be performed. There
are three major types of vascular access for maintenance
hemodialysis: primary arteriovenous (AV) fistulas;
synthetic arteriovenous fistulas (AV grafts); and double-
lumen, cuffed tunneled catheters. To facilitate placement
of a permanent vascular access, patients be referred to
an access surgeon when the patient has late stage 4 CKD,
defined by an estimated GFR of less than 20 to 25 mL/min
per 1.73 m2 [75]. Referral of patients with CKD to a
transplant center should occur when the GFR decreases to
less than 30 mL/min or, among diabetics, when the GFR is
between 30 to 40 mL/min.
References
1. Agarwal SK, Dash SC, Irshad M et al. Prevalence of
chronic renal failure in adults in Delhi, India Nephrol
Dial Transplant 2005; 20: 1638–1642
2. Data from: National Kidney Foundation. K/DOQI
clinical practice guidelines for chronic kidney
disease: evaluation, classification, and
stratification. Am J Kidney Dis 2002; 39(2 Suppl
1):S1.
3. Ikizler, IA. Nutrition and kidney disease. In: Primer
on Kidney Diseases, Greenberg, A (Ed), Elsevier
Saunders, Philadelphia, 2005, p. 496.
4. Orth SR. Effects of smoking on systemic and
intrarenal hemodynamics: influence on renal
function. J Am Soc Nephrol 2004; 15 Suppl 1:S58.
5. Orth SR, Hallan SI. Smoking: a risk factor for
progression of chronic kidney disease and for
cardiovascular morbidity and mortality in renal
patients--absence of evidence or evidence of
absence? Clin J Am Soc Nephrol 2008; 3:226.
6. Uribarri J, Douyon H, Oh MS. A re-evaluation of the
urinary parameters of acid production and
excretion in patients with chronic renal acidosis.
Kidney Int 1995; 47:624.
7. Widmer B, Gerhardt RE, Harrington JT, Cohen JJ.
Serum electrolyte and acid base composition. The
influence of graded degrees of chronic renal
failure. Arch Intern Med 1979; 139:1099.
8. de Brito-Ashurst I, Varagunam M, Raftery MJ,
Yaqoob MM. Bicarbonate supplementation slows
progression of CKD and improves nutritional
status. J Am Soc Nephrol 2009; 20:2075.
9. Locatelli F, Valderrábano F, Hoenich N, et al. The
management of chronic renal insufficiency in the
conservative phase. Nephrol Dial Transplant
2000; 15:1529.
10. Delmez JA, Slatopolsky E. Hyperphosphatemia:
its consequences and treatment in patients with
chronic renal disease. Am J Kidney Dis 1992;
19:303
11. National Kidney Foundation. K/DOQI clinical
practice guidelines for bone metabolism and
disease in chronic kidney disease. Am J Kidney Dis
2003; 42:S1.
12. Modified from National Kidney Foundation
DOQI™ Kidney Disease Outcomes Quality
Initiative. Am J Kidney Dis 43:S1–S201, 2004.
13. Stefanski A, Schmidt KG, Waldherr R, Ritz E. Early
increase in blood pressure and diastolic left
ventricular malfunction in patients with
glomerulonephritis. Kidney Int 1996; 50:1321.
14. Kopple JD, Greene T, Chumlea WC, et al.
Relationship between nutritional status and the
glomerular filtration rate: results from the MDRD
study. Kidney Int 2000; 57:1688.
15. Garg AX, Blake PG, Clark WF, et al. Association
between renal insufficiency and malnutrition in
older adults: results from the NHANES III. Kidney
Int 2001; 60:1867.
16. Ahmed, K, Kopple, J. Nutritional management of
renal disease. In: Primer on Kidney Diseases,
Greenberg, A (Ed). Academic Press, San Diego,
CA, 1994, p. 289.
17. Stack AG. Impact of timing of nephrology
referral and pre-ESRD care on mortality risk
among new ESRD patients in the United States.
Am J Kidney Dis 2003; 41:310.
18. Kessler M, Frimat L, Panescu V, Briançon S. Impact
of nephrology referral on early and midterm
outcomes in ESRD: EPidémiologie de l'Insuffisance
REnale chronique terminale en Lorraine (EPIREL):
results of a 2-year, prospective, community-
based study. Am J Kidney Dis 2003; 42:474.
19. Khan SS, Xue JL, Kazmi WH, et al. Does
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survival after initiation of dialysis? Kidney Int
2005; 67:1038.

Dr NP Singh
Director
Medicine & Allied Specialties
Sr Consultant in Nephrology
& Medicine
Pushpanjali Crosslay Hospital
Delhi-NCR
Vol. 11, Issue 4, October 2012
Contrast and the Kidney
Introduction
Technical development and increasing
availability of interventional procedures
has led a large number of patients to
being exposed to iodinated contrast
medium. There is a paucity of data on
patients undergoing such procedures in
India. Figures available for other
countries, such as USA, suggests that on a
average there are more than 13,22,000
diagnostic cardiac catheterizations and
12,65,000 percutaneous transluminal
coronary angioplasty procedures, which
is just two of the many ways in which
contrast is used. Regular use of the
contrast agents in imaging modalities
exposes patients to risks associated with
the use of these agents. Contrast induced
nephropathy (CIN) is one such threat, a
potentially avoidable adverse event
related with the use of iodinated contrast
media (ICM). In addition, it is the third
most general cause of hospital-acquired
acute renal failure. Patients with pre-
existing risk factors such as severe renal
insufficiency at baseline with or without
diabetes, advanced age, congestive
heart failure and dehydration, are more
likely to be at-risk. These complications
are important as the consequences are
serious or even life threatening. Thus, it is
impor tant implement preventive
strategies, and to have a knowledge of
the clinical presentation and subsequent
management of the condition.
Definition
The definition, provided by EUSR
(European Union Special Representative)
guidelines implies “Impairment in renal
function (an increase in serum
creatinine by more than 25%)
occurring within 3 days following the
intravascular administration of
contrast media and the absence of
Dr NP SIngh
alternative etiology”.
An arbitrary range of values of between
25% and 50% (an increase in absolute
values of 0.5–1.0 mg/dL) increase in
serum creatinine levels from baseline has
been suggested to define contrast-
induced nephropathy. Other suggested
definitions include the following: a rise in
serum creatinine levels of more than
100%, a rise in serum creatinine levels of
more than 1 mg/dL, a postprocedural
serum creatinine level greater than 5
mg/dL, or acute renal failure requiring
dialysis.
Contrast Agents
Various contrast agents used in clinical
practice are summarized in Table 1.
Epidemiology
The incidence of contrast-induced
n e p h ro p a t hy va r i e s m a r ke d l y,
depending on the definition used and on
other variables such as the type of
radiology procedure performed, the
dose and type of contrast agent
administered, the differing patient
populations in regard to number and
type of risk factors, and the length of
patient follow-up. An overall incidence
of 14.5% was recently quoted in a large
epidemiologic study but rates may vary
from 0% to 90%, depending on the
presence of risk factors. Incidence
among patients with diabetes has been
reported to be 9–40% in patients with
mild-to-moderate CKD and 50–90% in
those with severe CKI. The incidence in
the general population is much lower
and has been calculated to be less than
2%.
The in-hospital mortality rates were
1.1% for patients with no contrast-
induced nephropathy compared with
7.1% for those with nephropathy alone,
Table 1. Classification of contrast agents [10] Some important risk factors are summarized below.
1. Chronic Kidney Disease
High Low- Iso- Irrespective of cause, preexisting impairment of renal
osmolar osmolar osmolar
function appears to be the most important risk factor. The
(≈2,000 (600 to 900 (≈300
risk of CIN is inversely related to the calculated
mOsm/L) mOsm/L) mOsm/L)
estimated GFR (eGFR). An eGFR of <60 ml/ min/1.73
Ionic Iothalamate Ioxaglate m2 represents significant renal dysfunction and is used to
Diatrizoate define the patient at high risk for developing CIN.
Metrizoate

Non-ionic - Iohexol Iodixanol 2. Diabetes Mellitus

(Omnipaque) (Visipaque) Diabetes mellitus with associated renal insufficiency has
Ioversol
Iopamidol been identified as an independent risk factor for contrast
Iopromide nephropathy, with as many as 56% of those who develop
Ioversol the condition progressing to irreversible renal failure.
Diabetes itself is not an independent risk factor for the
and up to 35.7% for those with nephropathy requiring development of contrast-induced nephropathy. More
dialysis. Similar findings were noted in a study of more recent research has failed to corroborate this connection.
than 16,000 patients undergoing contrast-enhanced For example, in a prospective trial of patients with
examinations (CT of the head and body, cardiac diabetes none of the 85 patients with diabetes and
angiography, and peripheral angiography). normal renal function developed clinically significant
renal impairment (defined as an increase of > 50% in
Risk Factors serum creatinine levels).

3. Reduction of Effective Intravascular volume

Table 2: Risk factors associated with CIN Reduction of effective intravascular volume (due to
congestive heart failure, liver cirrhosis, or abnormal fluid
Non-modifiable risk
losses), prolonged hypotension (especially when induced
factors
Diabetes mellitus
by intensive antihypertensive treatment combined with
Renal disease or Solitary angiotensin-converting enzyme inhibitors and diuretics,
kidney most notably furosemide), and dehydration have been
Age >70 yrs reported as contributing to prerenal reduction in renal
Previous chemotherapy perfusion, thus enhancing the ischemic insult of contrast
Organ transplant
Cardio-Vascular disease
media.
- hypertension,
- congestive heart disease 4. Nephrotoxic Drugs
Directly nephrotoxic drugs (eg, cyclosporine A,
- cardiac or peripheral vascular disease aminoglycosides, amphotericin, and cisplatin), those that
HIV
inhibit the local vasodilatory effects of prostaglandins
Protein urea
(eg, nonsteroidal antiinflammatory drugs [NSAIDs]) and
Modifiable risk factors diuretics especially furosemide (due to intravascular
Type and volume of contrast media injected volume depletion), have been reported to render the
Sepsis or acute hypotension kidney more vulnerable to nephrotoxic contrast agents.
Dehydration or volume contraction
- CHF - Cirrhosis
Although all these medications are known to induce renal
- Nephrotic syndrome - Diuretics especially furosemide damage, their individual roles as independent risk
- Fluid losses factors of contrast-induced nephropathy have yet to be
Nephrotoxic Drugs – determined in large prospective clinical trials.
- Loop diuretics - Amphotericin B
- Aminoglycosides - Vancomycin
5. Multiple Myeloma
- NSAIDs
Multiple myeloma has been reported as a risk factor for
Vol. 11, Issue 4, October 2012
CIN. It has been argued that high amounts of protein in the
tubular lumen with concomitant contrast material load
may cause an obstructive nephropathy, a mechanism that
is thought to be central to the development of renal
insufficiency in patients with nephrotic-range proteinuria
secondary to multiple myeloma.
6. Contrast agents related factors
Volume of contrast agent
Large doses and multiple injections of contrast media
within 72 hours increase the risk of the patient's
developing contrast-induced nephropathy. However, cut-
off values have not been defined, yet.
Route of administration
The route of administration is also important, with contrast
media being more nephrotoxic when administered
intraarterially. This effect is thought to be due to the fact
that the acute intrarenal concentration of contrast media is
much higher after intraarterial rather than IV injection.
Osmolarity
Similarly, the osmolarity of the contrast media plays an
important role with large clinical studies and meta-
analyses indicating that the use of an LOCM substantially
reduces the risk of nephropathy in high-risk patients
compared with the use of HOCM. LOCM causes less
discomfort and fewer cardiovascular and anaphylactic
adverse reactions than HOCM but is more expensive.
Risk Assessment
Since occurrence of CIN is highly related to presence of
preprocedural risk factors, many attempts have been
made to develop a risk assessment score. The European
Society of Urogenital Radiology recommends that only
elevated serum creatinine levels (particularly secondary
to diabetic nephropathy), dehydration, congestive heart
failure, age greater than 70 years, and concurrent
nephrotoxic drugs be used to establish risk.
Cochran et al presented a point system (tally of risk
factors) model to predict the probability of developing
contrast-induced renal insufficiency. They found five risk
factors that were shown to predict at-risk patients with
high probability. These are:
1. Age > 55 years
2. Proteinuria
Vol. 11, Issue 4, October 2012
3. Abnormal baseline serum creatinine level
4. The use of HOCM [meglumine diatrizoate]
5. Preexisting renal disease.
These authors showed that the probability of developing
the condition increased as the number of factors
increased, with the most marked jump in serum creatinine
levels seen when three or more risk factors were present
(from < 5% increase with two factors to > 30% increase
with three factors).
Pathogenesis
The exact underlying mechanisms of nephrotoxicity have
yet to be fully elucidated but are likely to involve the
interplay of several pathogenic factors (Fig 2). Intrinsic
causes include the following: increased vasoconstrictive
forces, decreased local prostaglandin- and nitric oxide
(NO)-mediated vasodilatation, a direct toxic effect on
renal tubular cells with damage caused by oxygen free
radicals, increased oxygen consumption, and increased
intra tubular pressure secondary to contrast-induced
diuresis, increased urinary viscosity, and tubular
obstruction, all culminating in renal medulla ischemia.
Intrinsic causes act in concert with harmful extrinsic (pre
renal) causes such as dehydration and decreased
effective intravascular volume.
Clinical Feature
Clinical Features and Treatment
Contrast-induced nephropathy most commonly manifests
as a nonoliguric and asymptomatic transient decline in
renal function. The serum creatinine level begins to rise
within 24 hr of contrast administration, usually peaks
within 3–5 days, and returns to baseline within 10–14
days. Oliguric acute renal failure requiring hemodialysis
can also occur. This condition presents with oliguria (24-hr
urine volume < 400 mL) within 24 hours of contrast
administration and typically persists for 2–5 days.
Morbidity and mortality rates are significantly higher in
this group of patients when compared with those who
have nonoliguric renal failure.
Urinary epithelial cell casts, debris, and urate and calcium
oxalate crystals are nonspecific findings in contrast-
induced nephropathy. Low urinary sodium and fractional
excretion of sodium (< 1%) have been reported as being
distinctive characteristics of this condition, but these
 Contrast Media
­ PGE ­ Endothelin
­ Vasopressin
­ ANP
­ Adenosine ¯ PGI2
¯Blood flow
Direct cellular toxicity
Contrast induced nephropathy (CIN)
ANP, atrial natriuretic peptide; PGE, prostaglandin; PGI, prostacyclin
findings have not consistently been shown to be specific for
contrast-induced nephropathy. A persistent nephrogram
on radiography or CT 24 hours after contrast
administration is also said to be suggestive of a diagnosis
of contrast-induced nephropathy but is not a consistent or
a specific finding.
Treatment of established contrast-induced nephropathy
should start with the recognition of renal impairment after
the study. In patients at higher risk, renal function should be
carefully monitored by measuring serum creatinine levels
before and once daily for 5 days after the radiographic
procedure. After contrast-induced nephropathy is
identified, the subsequent management of this condition is
the same as that for acute renal failure due to other
causes. Admission to the hospital and subsequent judicious
monitoring of serum electrolyte levels are required to
prevent hyperkalemia, hyponatremia,
hyperphosphatemia, hypocalcemia, and metabolic
acidosis associated with acute renal failure. More severe
cases may require temporary hemodialysis, but a minority
of patients who do not respond to conservative treatment
will require permanent dialysis or kidney transplantation.
Preventive Treatments
Several drug interventions based on one or more of the
pathogenic mechanisms outlined earlier, have been tested
in trials for prophylaxis against the development of
contrast-induced renal dysfunction.
Vol. 11, Issue 4, October 2012
Systemic
Hypoxaemia ­ Osmotic load
­ Blood viscosity Distal tubule
¯O2 delivery O2 consumption
Renal medullary hypoxia
1. Hydration
Hydration is the primary intervention for preventing
contrast nephropathy. Several studies both in animals, and
humans have demonstrated hydration with saline infusions
to be beneficial in preventing contrast-induced
nephropathy.
More recently a prospective, single-center randomized
trial of 119 patients by Merten et al has suggested that
the use of sodium bicarbonate hydration is superior to
sodium chloride hydration. Rates of contrast-induced
nephropathy were significantly lower in the sodium
bicarbonate group (1.7%, n = 1) when compared with the
sodium chloride group (13.6%, n = 8) when both cohorts
were administered 154 mEq/L of either solution IV.
2. N -ACETYLCYSTEINE
There is some evidence that reactive oxygen species have
a role in renal damage caused by contrast agents [57, 74, 77-78].
N-acetylcysteine (NAC), a thiol-containing antioxidant, is
thought to act either as a free-radical scavenger or as a
reactive sulfhydryl compound that increases the reducing
capacity of the cell. NAC has been shown to ameliorate
ischemic renal failure in the animal model[84] and has been
used successfully to reduce the toxic effects of a variety of
experimentally or clinically induced ischemia-reperfusion
syndromes of the heart, kidney, lung, and liver [85-86].
In a recent meta-analysis of 41 randomized trials that
administered N-acetylc ysteine, theophylline,
fenoldopam, dopamine, iloprost, statin, furosemide, or
mannitol to the treatment group; found that preprocedural
treatment with N-acetylcysteine was more effective in
reducing the risk for contrast-induced nephropathy than
the hydration alone.
These recent studies, coupled with the favorable side
effect profile of NAC and its low cost, mean that NAC has
gained favor in many centers as a preventive therapy,
particularly in the high-risk group undergoing coronary
interventions.
More recently, Briguori et al [98] reported a protective
effect of a high dose (1,200 mg twice daily) versus a
standard dose (600 mg twice daily) along with saline
hydration.
3. Contrast Media
Low osmolar contrast media have been shown to be
associated with reduced risk of nephropathy especially in
high risk patients.
With the introduction of low-osmolar and iso-osmolar
contrast media, a reduction in the incidence of CIN has
been observed [4, 8, 50-53]. Low-osmolar contrast media have
gained widespread clinical acceptance because of fewer
adverse effects than high-osmolar contrast media,
particularly in high-risk patients with an elevated
preprocedural serum creatinine. The Rudnick
demonstrated that patients with preexisting renal
insufficiency alone or combined with diabetes mellitus had
a significantly lower risk of CIN when low-osmolar contrast
media are used.
4. Diuretics
It has previously been recommended that furosemide or
mannitol administered in conjunction with a saline infusion
offers better protection of renal function, but consistent
results have not been obtained. Indeed, an exacerbation
of contrast-induced nephropathy (defined as an
increased of > 0.5 mg/dL of serum creatinine levels)
occurred with the concomitant use of furosemide.
5. Theophylline
Adenosine, a potent vasoconstrictive agent, has been
implicated as a mediator in tubulo-glomerular feedback,
a mechanism that may have a role in the pathogenesis of
contrast-induced nephrotoxicity. Theophylline acts as a
nonspecific adenosine receptor antagonist and may be
given as an IV bolus of 2.5–5 mg/kg of body weight
before administration of contrast agent or orally for three
consecutive days before contrast injection.
Vol. 11, Issue 4, October 2012
6. Dopamine agonists
Dopamine is a potent vasodilator of the renal arteries. It
has been found to not benefit in any treatment but like
diuretics, dopamine had a deleterious rather than a
protective effect on renal function in patients with
diabetes.
Recent evidence show a selective dopamine type 1
receptor agonist, fenoldopam mesylate, may be useful in
preventing contrast-induced nephropathy. It produces
vasodilatation in vessels rich in dopamine type 1
receptors such as renal, mesenteric, and peripheral
arteries but does not stimulate dopamine type 2 or
adrenergic receptors, even at high doses. It is a potent
relaxant of glomerular arterioles, preferentially acting
on the efferent arterioles, and is six times more potent
than dopamine in increasing renal blood flow.
Observational studies reported rather low rates of CIN in
high-risk patients treated with fenoldopam. In a double-
blind, randomized, placebo-controlled pilot trial, the
combination of fenoldopam and hydration, compared
with hydration alone, resulted in an increase in renal
plasma flow, a decrease in peak serum creatinine level 72
hours after exposure to contrast media, and a trend
toward decreased incidence of CIN (21% and 41%,
respectively; p=0.14). Two other prospective randomized
trials showed negative results.
7. Hemodialysis and Hemofiltration
Several studies examined the effect of hemodialysis,
immediately after exposure to contrast media, in
preventing renal function deterioration in patients with
preexisting renal disease. All these studies provided
consistent results, showing that prophylactic hemodialysis
does not diminish the rates of CIN.
Two studies by Marenzi et al [112-113] investigated the effect
of continuous venovenous hemofiltration in prevention of
CIN in patients with severe chronic renal insufficiency
(serum creeatinine >2 mg/dL) in comparison with
intravenous hydration. Increase of creatinine >25% and
inhospital mortality were significantly lower in group with
hemofiltration.
Guidelines for Prevention
Since occurrence of CIN is proportionately related to
presence of risk factors, it essential is to estimate the
patient's risk for CIN. The commonly used methods for
identifying patients at risk include use of patient
questionnaires, review of medical history and
measurement of SCr levels prior to administration of CM.
Calculation of the eGFR should be encouraged.
In case of low risk patients, good oral hydration is all that
required. For high risk cases, optimal strategy for
General guidelines for all patients with GFR <60 mL/min:
· Consider alternate imaging studies not requiring
iodinated contrast medium (CM).
· Hold nephrotoxic drugs for 48 hours prior to CM.
· Use iso-osmolar or low-osmolar CM.
· Avoid high-osmolar CM.
· Minimize contrast volume and avoid repeat contrast
studies within 72 hours if possible
Moderate-to-High risk for CIN
· IV 0.9% Saline or NaBicarb
· Follow-up GFR 48 hours post CM
Fig 3: Algorithm for prevention of CIN
(adapted and modified from the consensus guidelines
developed by Canadian Association of Radiologists [129]
Table 4: Dose of peri-procedural Intravenous fluids
to prevent CIN [87]
IVF = 1 mL/kg/hr 12 hours pre & 12 hours post contrast*
(24 hour total infusion duration)
(*NS preferred IVF )
CHF or left ventricular ejection fraction (LVEF) < 40%?
0.5 ml/kg/hr 12 hrs pre & post contrast (24 hour total
infusion duration)
Emergent procedure?
Fluid bolus of 500-1000 ml prior to procedure. Hydration
during procedure and/or 12 hrs afterward. [ if possible]
(dependent on clinical status)
Table 5: Dose of Bicarbonate to prevent CIN [130]
IVF = 150 mEq of sodium bicarbonate in 1 liter of D5W
3 ml/kg bolus 1 hour prior to procedure AND 1 mL/kg/hour
during and for 6 hours post-procedure
Glycemic control issues (including patients with
diabetes)?
Consider mixing sodium bicarbonate in 1 liter of sterile
water instead of D5W
Vol. 11, Issue 4, October 2012
preventing CIN has not been fully established; yet several
preventive measures are supported by clinical trial data.
Fig 3 provides an algorithm adapted from guidelines
developed by Canadian Association of Radiologists,
outlining the management of patients undergoing contrast
procedures.
Table 6: Dose of N-Acetylcysteine to prevent CIN [131]
Tolerating PO intake?
600-1200 mg capsules PO Q12h X 4 doses
2 doses pre-contrast and 2 doses post-contrast is optimal
Feeding tube or NG-access?
Acetylcysteine 600-1200 mg (3 mL of 20% soln.) liquid
PT/NG Q12h x 4 doses total
Emergent Procedure?
1 dose before and 3 doses post cath or procedure is
acceptable (Q12h x 4 doses total)
IV Acetylcysteine?
600-1200 mg IV x 1 over 15 minutes, then 600-1200 mg
PO/PT q12h x 4 doses post-procedure:
For a high risk patient with acute ST-elevation MI
undergoing cardiac catheterization.
Guidelines for patients taking Metformin
The biguanide metformin are used in non-insulin
dependent diabetes mellitus. Approximately 90% of
metformin is eliminated via the kidneys in 24-hour Renal
insufficiency (GFR<70 ml/min) will lead to retention of
these biguanides in the tissues and the potential for the
development of fatal lactic acidosis [132]. The use of
contrast media in patients receiving metformin should be
carried out with care. Contrast media can induce a
reduction in renal function, leading to retention of
metformin that may induce lactic acidosis. There is no
conclusive evidence indicating that the intravascular use
of contrast media precipitated the development of
metformin induced lactic acidosis in patients with normal
renal function. The complication has almost always been
observed in Type 2 diabetic patients with abnormal renal
function before injection of contrast media. Serum
creatinine should always be monitored to check that it is
within the normal range before administration of
metformin is resumed. The CMSC of the ESUR (Table 7) has
produced a new guideline on the use of metformin and
contrast media.
Table 7: European Society of Urogenital Radiology
(ESUR) guidelines for the administration of contrast
media to diabetics taking metformin [3]
1. Serum creatinine level should be measured in every
diabetic patient treated with biguanides prior to
intravascular administration of contrast media. Low-osmolar
contrast media should always be used in these patients.
2. Elective studies
a) If the serum creatinine is normal, the radiological
examination should be performed and intake of
metformin stopped from the time of the study. The use of
metformin should not be resumed for 48 h and should
only be restarted if renal function/serum creatinine
remains within the normal range.
b) If renal function is abnormal, the metformin should be
stopped and the contrast study should be delayed for 48
h. Metformin should on be restarted 48 h later, if renal
function/serum creatinine is unchanged.
3. Emergency cases
a) If the serum creatinine is normal, the study may proceed
as suggested for elective patients.
b) If the renal function is abnormal (or unknown), the
physician should weigh the risks and benefits of contrast
administration.
Alternative imaging techniques should be considered. If
contrast media administration is deemed necessary and the
following precautions should be implemented:
· Metformin therapy should be stopped
· The patient should be hydrated, eg, at least 100 ml h21
of soft drinks or intravenous saline up to 24 h after
contrast medium administration – In warm areas more
fluid should be given
· Monitor renal function (serum creatinine), serum lactic
acid and pH of blood
· Look for symptoms of lactic acidosis (vomiting,
somnolence, nausea, epigastric pain, anorexia,
hyperpnoea, lethargy, diarrhea and thirst). Blood test
results indicative of lactic acidosis: pH<7.25 and lactic
acid >5 mmol
References
1. Heart Disease and Stroke Statistics 2008 Update:
A Report from the American Heart Association
Statistics Committee and Stroke Statistics
Subcommittee. Circulation 2008; 117: e133-137
2. Tublin ME, Murphy ME, Tessler FN. Current concepts
in contrast media-induced nephropathy. AJR1998;
171:933-939.
3. Morcos SK, Thomsen HS, Webb JAW and members
of contrast media safety committee of the
European Society of Urogenital Radiology (ESUR).
Vol. 11, Issue 4, October 2012
Contrast media induced nephrotoxicity: A
c o n s e n s u s r e p o r t . E u r Ra d i o l 1 9 9 9 ;
9:1602–1613.
4. Gleeson TG, Bulugahapitiya S. Contrast-Induced
Nephropathy. AJR 2004; 183:1673-1689
5. Katzberg RW. Urography into the 21st century:
new contrast media, renal handling, imaging
characteristics, and nephrotoxicity. Radiology
1997; 204: 297–312.
6. Parfrey PS, Griffiths SM, Barrett BJ, et al Contrast
material-induced renal failure in patients with
diabetes mellitus, renal insufficiency, or both.
NEJM 1989; 320:143-153
7. McCullough PA, Wolyn R, Rocher LL, Levin RN,
O'Neill WW. Acute renal failure after coronary
intervention: incidence, risk factors, and
relationship to mortality. Am J Med1997;
103:368-374
8. Lautin EM, Freeman NJ, Schoenfeld AH, et al
Radiocontrast-associated renal dysfunction: a
comparison of lower-osmolality and conventional
high-osmolality contrast media. AJR1991;
157:59-65
9. Levy EM, Viscoli CM, Horwitz RI. The effect of
acute renal failure on mortality: a cohort analysis.
JAMA1996; 275:1489-1494
10. Kozak M, Robertson BJ, Chambers CE. Cardiac
catheterization laboratory: Diagnostic and
therapeutic procedures in the adult patient. In:
Kaplan, JA, editor. Kaplan's Cardiac Anesthesia,
5th ed. p. 307.
11. Schwab SJ, Hlatky MA, Pieper KS, et al Contrast
nephrotoxicity: a randomized controlled trial of a
nonionic and an ionic radiographic contrast
agent. N Engl J Med 1989; 320:149–153
12. Rudnick MR, Goldfarb S, Wexler L, et al
Nephrotoxicity of ionic and nonionic contrast
media in 1,196 patients: a randomized trial—the
Iohexol Cooperative Study. Kidney Int 1995;
47:254–261
13. Weisberg LS, Kurnik PB, Kurnik BR. Risk of
Radiocontrast nephropathy in patients with and
without diabetes mellitus. Kidney Int 1994;
45:259–265
14. Cochran ST, Wong WS, Roe DJ. Predicting
angiography- induced acute renal function
impairment: clinical risk model. AJR 1983;
141:1027–1033
15. Harkonen S, Kjellstrand CM. Exacerbation of
diabetic renal failure following intravenous
pyelography. Am J Med 1977;63:939–946
16. Manske CL, Sprafka JM, Strony JT, Wang Y.
Contrast nephropathy in azotemic diabetic
patients undergoing coronary angiography. Am J
Med 1990; 89:615–620
 An Approach to the patient with Obstructive Kidney Disease
Dr Shailesh Chandra Sahay

Obstruction of the urinary tract can occur
before or after birth. The cause of
obstruction may be congenital or
acquired and benign or malignant. The
site of obstruction can vary from
pelvicalyceal system to urethral meatus.
The severity of the obstruction is related
with the extent or degree of obstruction
(partial or complete, unilateral or
bilateral), its chronicity (acute or chronic)
and the baseline condition of the kidneys.
These may ultimately lead to permanent
renal damage.
Hydronephrosis is the dilation of the
renal pelvis or calyces. It may be
associated with obstruction but may be
present in the absence of obstruction.
Table 1. Etiology of Obstructive Uropathy
Obstructive uropathy refers to the
functional or anatomic obstruction of
urinary flow at any level of the urinary
tract. Obstructive nephropathy is
present when the obstruction causes
functional or anatomic renal damage.
Clinical feature
The clinical signs and symptoms of
obstructive uropathy are variable. It
depends upon the time course over which
it develops and whether or not both sides
are involved. Acute unilateral
obstruction presents with symptoms of
renal colic. Chronic unilateral obstruction
is clinically silent and diagnosed on
incidental detection of hydronephrosis
on imaging. Acute or chronic bilateral

Site of obstruction Etiology

Kidney Congenital disease- PCKD, Primary Pelviureteric junction (PUJ)
obstruction, Renal cyst, Aberrant vessels at PUJ

Neoplastic- Wilm's tumor, renal cell carcinoma, Upper tract

Dr Shailesh Chandra Sahay
Consultant Urologist
Department of Urology
Pushpanjali Crosslay Hospital
NCR-Delhi
transitional cell carcinoma, multiple myeloma
Inflammatory- Tuberculosis, Echinococcus infection
Metabolic- stone
Traumatic
Ureter Congenital- Stricture, ureterocele, ureterovesical reflux,
ureteral valve, ectopic kidney, preureteric vena cava, Prune-
belly syndrome
Neoplastic- TCC of ureter, Metastatic
Inflammatory- Tuberculosis, Schistosomiasis, Abscess,
Endometriosis,
Miscellaneous- retroperitoneal fibrosis, Pelvic lipomatosis,
Aortic aneurysm, Urinoma, Pregnancy, Lymphocele
Bladder and Urethra Congenital- Posterior urethral valve, phimosis,
urethral stricture, hypospadias and epispadias, hydrocolpos
Neoplastic - Bladder carcinoma, prostate carcinoma,
carcinoma of urethra and penis
Inflammatory- Prostatitis, paraurethral abscess
Miscellaneous- Benign prostatic hypertrophy (BPH),
neurogenic bladder

Vol. 11, Issue 4, October 2012

obstruction presents with decrease urine output and
uraemia. Patient usually presents with vague symptoms of
flank discomfort, vomiting, feelings of fullness, nonspecific
lethargy and urinary tract infection. Vomiting is induced
by increased ureteral pressure that leads to increases
pyloric sphincter pressure hence interfering with gastric
motility (renogastric reflex).
Diagnosis
Ultrasonography
Renal ultrasonography is the initial investigation in the
evaluation of suspected urinary tract obstruction. It gives
information about renal parenchymal thickness,
pelvicalyceal system dilatation. Hydronephrosis is an
anatomic diagnosis. However, caliectasis and pelviectasis
both may be present in an unobstructed system. Renal
sinus cysts can give false impression as hydronephrosis.
Conversely, hydronephrosis may not be prominent early in
acute obstruction. Presence of an intrarenal collecting
system or dehydration may lead to false-negative
interpretations. Ultrasonography has 35% false-negative
rate in acute obstruction, underscoring the need to
correlate the clinical picture carefully with the radiologic
findings1.
Table 2. Investigations in Obstructive Uropathy
Investigation Utility
Ultrasound abdomen Detects hydronephrosis, urinary
tract stones Measure renal
parenchymal thickness, residual
urine volume in bladder, prostate
size, renal resistive index.
Doppler ultrasonography gives an indication of functional
status of kidney. It allows measurement of the renal
resistive index (RI), which has been used as a parameter to
assess renal obstruction. The RI is defined as peak systolic
velocity (PSV) minus the end-diastolic velocity (EDV)
divided by the PSV. Values greater than 0.7 reflects
elevated resistance to blood flow and thus suggesting
obstructive uropathy2. Doppler determination of RI is a
valuable adjunct to routine sonographic evaluation of
urinary tract.
Excretory Urography/ Intravenous pyelography
Intravenous pyelography (IVP) has been considered as the
“gold standard” for the evaluation of the upper urinary
tract. Now-a-days, it has been gradually supplanted by
other modalities for many of its prior indications. It
provides both anatomic and functional information. Acute
urinary obstruction may be inferred from the functional
abnormality of a delayed nephrogram and pyelogram on
the affected side. Delayed images may then ultimately
reveal the anatomic level of obstruction. Parenchymal
thinning, extreme calyceal blunting, and ureteral
tortuosity may indicate the chronicity of obstruction.
The utility of IVP is limited in those with renal insufficiency.
Furthermore, the risk of contrast nephropathy increases
with increasing serum creatinine. IVP, therefore, should not
be performed in patients with renal insufficiency, those at
higher risk for developing contrast-induced nephropathy,
or those with history of contrast allergy. Radiation
exposure limits its utility in pregnancy3.

Intravenous Functional and anatomical Retrograde Pyelography

pyelography information of kidneys and
urinary (IVP) tract
Retrograde pyelography (RGP) accurately defines
ureteral and pelvicalyceal system anatomy. It defines the
Retrograde Defines ureteral and location of an obstructive lesion and its extent. It is useful in
pyelography pelvicalyceal system anatomy in
those cases where IV contast can
those who have renal insufficiency or have other risks for
not be given receiving intravenous iodinated contrast material

Whitaker test Detect and differentiate degree

Renal dynamic scan
Antegrade Pyelography
of urinary obstruction
This technique may be helpful when other imaging studies
Measure GFR and detect any do not adequately define collecting system or ureteral
obstruction in urinary drainage
anatomy and when RGP is not technically feasible.
from kidney

CT Scan and MRI An accurate method to detect Whitaker Test

abdomen urinary stones, mass, First described by Whitaker in 1973, this study involves
cyst. Urography provides an
anatomical picture of urinary measurement of renal pelvic pressure during infusion of
tract either saline or contrast material into the collecting system

Vol. 11, Issue 4, October 2012

through a percutaneous needle at a fixed rate of 10
mL/min4. A catheter is placed in the bladder to monitor
intravesical pressure, which is subtracted from the
measured collecting system pressures to calculate the
“true pressure” within the pelvis. A true intrapelvic
pressure of less than 15 cm H2O is considered normal,
greater than 22 cm H2O indicative of obstruction, and
between 15 and 22 cm H2O indeterminate. Although its
reliability to detect obstruction and differentiate degree
of obstruction has been established in animal models5.
Studies have reported a sensitivity and specificity of only
79% and 50% in kidney transplantation patients6.
Nuclear Renography/ Renal Dynamic scan
Renal dynamic scan is a useful, noninvasive test for
evaluating patients with suspected obstruction. It provides
a functional assessment without exposure to iodinated
contrast. Radiopharmaceuticals for renography are
selected on the basis of the function to be studied. The
glomerular agent Tc 99m DTPA and the tubular agent Tc
99m MAG3 are most commonly used. All tracers are
administered intravenously, and their uptake and
subsequent clearance is evaluated and quantitated
scintigraphically. From these data, relative renal function
can be calculated. Obstruction can be assessed by
measuring the clearance curves, either from a visual
assessment of the pattern or from calculation of the half-
time (time at which 50% of the tracer is eliminated from
the collecting system). By convention, a half-time less than
10 minutes is considered normal, greater than 20 minutes
is considered obstructed, and between 10 and 20 minutes
is equivocal. Tracer clearance can be spuriously delayed
because of renal insufficiency and the presence of
vesicoureteral reflux, and some have suggested that renal
immaturity in neonates may generate false-positive
studies7.
In order to detect obstruction, a high-flow state may be
necessary. Patients therefore should be well hydrated to
prevent misinterpretation related to low-flow states.
Theoretically, bladder catheterization should be
performed to maintain low intravesical pressure.
However, in clinical practice this is utilized only in certain
cases such as suspected lower urinary tract obstruction,
vesicoureteral reflux, neurogenic or noncompliant
bladder, or low-lying, pelvic kidneys from which the renal
s i g n a l m a y b e o b s c u r e d by i n t r a v e s i c a l
radiopharmaceutical7. Although an F +20 study is reliable
Vol. 11, Issue 4, October 2012
when obstruction is demonstrated, both the F-15 and F +0
sequences can induce obstructed patterns in previously
equivocal cases8.
CT Scan and MRI
This modality has now replaced IVP as an initial imaging
study in those with suspected ureteral obstruction,
especially in an acute setting. In their landmark study,
Smith and coauthors (1995) demonstrated the efficacy of
unenhanced spiral CT in the evaluation of possible
ureteral obstruction, prospectively comparing it with IVP In
the detection of ureteral calculi, CT has a sensitivity of
97%, specificity of 96%, and overall accuracy of 97%9.
At this time, CT is the most accurate radiologic study for the
diagnosis of ureteral calculi.
CT directly demonstrates calculi classically considered
radiolucent on X ray, including uric acid, xanthine,
dihydroxyadenine, and many drug-induced stones.
Exceptions, however, are calculi composed of protease
inhibitors, which are not visualized by CT 10. Secondary CT
signs of obstruction such as ureteral dilatation,
nephromegaly, perinephric stranding or fluid can
facilitate the diagnosis of acute obstruction.
The role of magnetic resonance urography (MRU) is still
being defined11. Although this study accurately identifies
hydroureteronephrosis, a limitation is its inability to
demonstrate either calculi or the ureteral anatomy of
unobstructed systems. However absence of ionizing
radiation has allowed its utilization in the assessment of
pregnant patients with hydronephrosis.
Management
Unilateral ureteral obstruction associated with urinary
tract infection or Pyonephrosis and bilateral ureteral
obstruction with renal failure should be immediately
drained.
Renal Drainage
There are two ways to drain the kidney in emergency
settings- Retrograde double J stenting and percutaneous
nephrostomy tube placement. These measures may allow
temporary drainage until a definitive procedure is
performed. Urine specimens for urinalysis and culture
should be obtained from the obstructed renal unit at the
time of relief of obstruction. Antibiotic therapy is started if
there are clinical signs and symptoms of infection.
 adults16. Sometime the patient may prefer life with a stent
or percutaneous nephrostomy.

Fig 1: Antegrade urinary diversion with PCN tube
The relative merits of indwelling ureteral stents and
percutaneous nephrostomy tubes have been evaluated by
several groups. Indwelling stents obviate the need for
external collection devices but are associated with
bothersome voiding symptoms. The choice of drainage
ultimately depends on the clinical setting. If the patient has
an uncorrectable coagulopathy or platelet abnormality,
ureteral stenting is indicated. There does not appear to be
a significant advantage of either approach in those
requiring drainage for stone-related problems12. 13.
Pain Management
The first-line therapy in the management of renal colic has
been parenteral administration of narcotic analgesics.
Nonsteroidal anti-inflammatory drugs (NSAIDs), however,
have assumed an increasing role in the acute management
of pain if renal function is normal. NSAIDs have been
demonstrated to reduce collecting system pressure. A
concomitant reduction in RBF induced by NSAIDs is thought
to be one of the mechanisms for decreasing collecting
system pressure17. There is also a downregulation of
aquaporin water channels associated with this COX-2
induction, and this promotes diuresis after obstruction is
relieved18.
The choice of pain management should be based on the
patient's clinical condition. NSAIDs should not be utilized in
patients with renal insufficiency as this could be
exacerbated by the induced reduction in RBF. COX-1
inhibitors should not be administered to patients at risk for
gastrointestinal bleeding or when optimal platelet
function is needed.

In difficult cases where retrograde stenting is unsuccessful,

Postobstructive Diuresis
antegrade stenting can be done through PCN. Ureteral
Mechanisms
stent placement typically requires greater x-ray
After the relief of urinary tract obstruction,
exposure as compared with percutaneous nephrostomy
postobstructive diuresis may occur. Urine outputs of 200
placement13. This may be of concern in pregnant patients,
mL/hr or greater may be encountered. Although this
particularly early in gestation when the fetus is most
occurs mainly after relief of BUO or obstruction of a
sensitive to radiation effects 14. Percutaneous nephrostomy solitary kidney, it can rarely occur when there is a normal,
should be strongly considered if pyonephrosis is
contralateral kidney19. The diuresis is a normal physiologic
suspected.
response to the volume expansion and solute accumulation
occurring during obstruction. Sodium, urea, and free
Choice of Surgical Intervention
water are eliminated and the diuresis subsides after
After the acute obstruction has been relieved, definitive
solute and fluid homeostasis is achieved20.
management is planned according to the cause of
obstruction and renal functional status. Endoscopic, open,
However, a “pathologic” postobstructive diuresis may
or laparoscopic ablative and reconstructive procedures
ensue, characterized by inappropriate renal handling of
may all be utilized. A less than 10% contribution to global
water or solutes, or both. It is due to a derangement of the
renal function has been proposed as the threshold for
medullary solute gradient and a number of altered
nephrectomy. The decision for nephrectomy should be
signaling and transport pathways. It is marked by poor
made only after the affected kidney has been
responsiveness of the collecting duct to ADH.
adequately drained for a 6 to 8 weeks15. In addition, GFR
of less than 10 mL/min/1.73 m2 in the affected kidney Clinical Management of Postobstructive Diuresis
successfully predicted renal function that did not stabilize Subjects in whom BUO or UUO in a solitary kidney is
or improve after surgical correction of obstruction in relieved should be monitored for a postobstructive
Vol. 11, Issue 4, October 2012
diuresis. Serum electrolytes, magnesium, blood urea
nitrogen (BUN), and creatinine should be monitored. This is
a physiologic diuresis in the majority of cases that resolves
when free water and excess solutes are eliminated. Serum
electrolytes, BUN, magnesium, and creatinine are checked
daily until the diuresis resolves. If patients have signs of
fluid overload, azotemia, or poor cognitive function or
hypotension, more intense monitoring should be done. The
clinically stable patient with good cognitive function
should be given free access to oral fluids. Those with poor
cognitive function should receive intravenous hydration but
below the normal maintenance amounts.
Key Message
Obstructive kidney disease is an emergency condition
which needs urgent evaluation and management. The
mainstay of diagnosis of this condition is kidney function
test, Ultrasound abdomen and if needed then CT Scan /
IVP. The obstruction requires immediate drainage of
kidney in the form of either percutaneous nephrostomy
(PCN) or Double J stenting. Hemodialysis is required to
stabilize the patient. A combined team approach of
Urologist, Nephrologist and radiologist is highly
recommended to treat such patients.
References
1. Laing FC, Jeffrey RB, Wing VW. Ultrasound versus
excretory urography in evaluating acute flank pain.
Radiology 1985; 154:613-16.
2. Platt JF, Ellis JH, Rubin JM: Examination of native
kidneys with duplex Doppler ultrasound. Semin
Ultrasound CT MR 1991; 12:308-18.
3. Zagoria R, Tung G: Genitourinary Radiology: The
Requisites, St. Louis: Mosby; 1997:2-6.
4. Whitaker RH: Methods of assessing obstruction in
dilated ureters. Br J Urol 1973; 45:15-22.
5. Ryan PC, Maher K, Hurley GD, Fitzpatrick JM: The
Whitaker test: Experimental analysis in a canine
model of partial ureteric obstruction. J Urol 1989;
141:387-390.
6. Sperling H, Becker G, Heemann U, et al: The
Whitaker test, a useful tool in renal grafts? Urology
2000; 56:49-52.
7. Karam M, Feustel PJ, Goldfarb CR, Kogan BA:
Diuretic renogram clearance half times in the
diagnosis of obstructive uropathy: Effect of age
and previous surgery. Nucl Med Commun 2003;
24:797-807.
Vol. 11, Issue 4, October 2012
8. Turkolmez S, Atasever T, Turkolmez K, Gogus O:
Comparison of three different diuretic renal
scintigraphy protocols in patients with dilated
upper urinary tracts. Clin Nucl Med 2004;
29:154-60.
9. Smith RC, Verga M, Dalrymple N, et al: Acute
ureteral obstruction: Value of secondary signs of
helical unenhanced CT. AJR Am J Roentgenol
1996; 167:1109-13.
10. Gentle DL, Stoller ML, Jarrett TW, et al: Protease
inhibitor-induced urolithiasis. Urology 1997;
50:508-11.
11. Rothpearl A, Frager D, Subramanian A, et al: MR
urography: Technique and application. Radiology
1995; 194:125-30.
12. Pearle MS, Pierce HL, Miller GL, et al: Optimal
method of urgent decompression of the collecting
system for obstruction and infection due to
ureteral calculi. J Urol 1998; 160:1260-64.
13. Mokhmalji H, Braun PM, Martinez Portillo FJ, et al:
Percutaneous nephrostomy versus ureteral stents
for diversion of hydronephrosis caused by stones:
A prospective, randomized clinical trial. J Urol
2001; 165:1088-92.
14. McAleer SJ, Loughlin KR: Nephrolithiasis and
pregnancy. Curr Opin Urol 2004; 14:123-27.
15. Kerr WS: Effect of complete ureteral obstruction
for one week on kidney function. J Appl Physiol
1954; 6:762-72.
16. Khalaf IM, Shokeir AA, El-Gyoushi FI, et al:
Recoverability of renal function after treatment of
adult patients with unilateral obstructive uropathy
and normal contralateral kidney: A prospective
study. Urology 2004; 64:664-68.
17. Perlmutter A, Miller L, Trimble LA, et al: Toradol, an
NSAID used for renal colic, decreases renal
perfusion and ureteral pressure in a canine model
of unilateral ureteral obstruction. J Urol 1993;
149:926-30.
18. Cheng X, Zhang H, Lee H, Park JM:
Cyclooxygenase-2 inhibitor preserves medullary
aquaphorin-2 expression and prevents polyuria
after ureteral obstruction. J Urol 2004;
172:2387-90.
19. Schlossberg SM, Vaughan Jr ED: The mechanism
of unilateral post-obstructive diuresis. J Urol
1984; 131:534-36.
20. Loo MH, Vaughan ED: Obstructive nephropathy
and postobstructive diuresis. AUA Update Series,
Lesson 9, Vol 4, 1985.
 Dialysis in Kidney Disease
Introduction
Kidney is the only organ in the body
whose function can be artificially
replaced. If damage occurs to kidneys,
the kidneys may become inefficient or
may stop functioning altogether. This
process may be acute or chronic.
Acute Kidney Injury: An acute injury to
kidneys can occur due to various causes
such as toxins, drugs, infection or immune
response. The subsequent damage is
largely reversible if the underlying cause
is removed. However, the process may
take days to weeks. Hence in this period,
dialysis may be required for patient's
survival.
Indications for dialysis in the patient with
acute kidney injury are:
1. Uremic complications, such as
pericarditis, encephalopathy, or
gastrointestinal bleeding.
2. Volume overload not treatable with
diuretics.
3. Severe hyperkalemia.
4. Resistant acidosis
5. Acute poisoning with a dialyzable
substance.
Chronic Kidney Disease: If an acute
kidney injury does not reverse, it may
progress to chronic stage. Chronic
damage to kidneys also occur due to
continuous insult from systemic diseases
such as Diabetes and Hypertension. In
suc h cases, the kidney function
Dr Sanjiv Mahajan
deterioates progressively. Finally, a
Senior Resident
stage is reached when survival is
Dr Sanjay Gupta
compromised and Renal Replacement
Additional Professor
Therapy is mandated.
Department of Nephrology
Indications for dialysis in the patient with
All India Institute of
chronic kidney disease:
Medical Sciences
In a CKD patient, dialysis is generally
New Delhi.
initiated when the estimated GFR falls
below 10mL/min. However, presence of
Vol. 11, Issue 4, October 2012
Dr Sanjiv Mahajan and Dr Sanjay Gupta
any of the following conditions mandates
early initiation of dialysis:
1. Fluid overload refractory to
diuretics
2. Hypertension poorly responsive to
antihypertensive medications
3. Refractory metabolic disturbances
such as hyperkalemia, metabolic
acidosis, hypercalcemia, hypo-
calcemia, and hyperphosphatemia
4. Persistent nausea and vomiting
5. Evidence of malnutrition
6. Pericarditis or pleuritis
7. U r e m i c e n c e p h a l o p a t hy o r
neuropathy
8. Bleeding diathesis
Renal Replacement Therapy is achieved
by:
1. Dialysis
2. Hemofiltration or
3. Renal transplantation.
Dialysis is divided into two broad
categories: Hemodialysis and Peritoneal
dialysis.
Hemodialysis
In Hemodialysis, waste products and
excess water are removed extra
corporeally using an ar tificial
semipermeable membrane-dialyser.
Principle
Dialysis utilizes two simple phenomenon
viz diffusion and convection for removal
of waste product and excess water. The
blood from the body passes over
semipermeable membranes in dialyzer
and the dialysate passes on the other
side of the semipermeable membrane.
Waste product diffuses into dialysate
along their concentration gradient.
Dialysate carries away the waste
products and excess water, and the
cleansed blood is returned to the
patient.
Requirements
1. Vascular access
2. Dialyser
3. Dialysate
4. Hemodialysis Machine
1. Vascular access: It is the site on the body where blood is
removed and returned during dialysis. The vascular
access should allow continuous high volumes of blood flow.
A vascular access may be temporary or permanent
a. Temporary vascular access:
I. Venous catheter: A venous catheter is placed in
jugular vein or femoral vein. In acute and emergency
conditions and in non ambulatory patients, femoral
vein may be used. Otherwise, jugular vein is used
which is safer and lasts longer. Catheter in subclavian
vein is now largely abandoned due to high incidence
of stenosis.
ii. Arterio-venous graft: An arteriovenous graft is a
synthetic tube made of Polytetrafluoroethylene
(PTFE) that is grafted between an artery and vein.
The graft becomes an artificial vein that can be used
repeatedly for needle placement and blood access
during hemodialysis. A graft can be used within 2 or 3
weeks after placement and can last several years.
b. Permanent vascular access:
Arterio-venous fistula (A-V fistula): It is made by joining an
artery and a vein. Fistulas are usually made in the
nondominant arm. They are generally created on the
following sites:
· On the dorsum of the hand below the thumb - the
'snuffbox' fistula: the dorsal branch of the radial
artery is anastomosed to the cephalic vein.
· The forearm - Brescia-Cimino fistula: the radial artery
is anastomosed to the cephalic vein.
· The elbow-Brachiocephalic fistula: the brachial
artery is anastomosed to the cephalic vein.
· A fistula takes on an average 4–6 weeks to mature.
2. Dialyser: The main element in a dialyser (Fig 1) is a
semipermeable membrane through which small molecules
can pass by diffusion. It consists of a cylindrical bundle of
hollow fibers, whose walls are composed of semi-
permeable membrane. It is then assembled into a clear
plastic cylindrical shell with four openings. One opening or
blood port at each end of the cylinder communicates with
each end of the bundle of hollow fibers. This forms the
"blood compartment" of the dialyzer. Two other ports are
cut into the side of the cylinder. These ports communicate
with the space around the hollow fibers and form the
Vol. 11, Issue 4, October 2012
Fig 1: Dialyser
"dialysate compartment." Blood is pumped via the blood
ports through this bundle of very thin capillary-like tubes
and the dialysate is pumped through the space
surrounding the fibers. Initial membranes were made of
cellulose. Cellulose acetate and modified cellulose
dialysers are still used. But most membranes are now
made from synthetic materials, using polymers such as
polyarylethersulfone, polyamide, polyvinylpyrrolidone,
polycarbonate, and polyacrylonitrile. The main
advantage of synthetic membranes is that they activate
complement to a lesser extent than cellulose membranes.
3. Dialysate: It is the fluid consisting of solutes that flow
through the dialyser. It helps in filtering out of the toxins
from the blood. A typical dialysate consists of the
following composition:
Glucose: 200mg/dL
Na:140 mEq/L
K: 1-3 mEq/L
Bicarbonate: 30-35 mEq/L
Ca: 2.5 mEq/L
Mg: 1mEq/L
The composition can be varied depending upon the
biochemical profile of the patient.
4. Hemodialysis Machine: It takes care of supplying the
blood and the dialysate to the dialyser (fig 2). It controls
the flow and the pressures and provides visual indication
and alarm when something goes wrong.
The blood pump takes the blood from the patient via the
vascular access and supplies it to the dialyser. The blood is
confined to the disposable plastic tubing and does not
come in contact with any part of the machine.
The dialysate pump mixes the concentrate with water and
moves the dialysate through the dialyser.
Procedure through the space surrounding the fibers. The impurities in
See fig 3. Blood from the body is pumped through the the blood like urea diffuse to the dialysate. Pressure
plastic tubing into the dialyser. The blood pump in the gradients are applied to move fluid from the blood to the
hemodialysis machine can control the rate of blood flow. It dialysate compartment (ultrafiltration). During
is generally kept in the range of 300-450 mL/min. To ultrafiltration, the solutes in the blood also move out by
prevent clotting, it is periodically mixed with heparin. convection. The purified blood is then returned to the
body. A typical hemodialysis session lasts 4 hours and
Simultaneously, the dialysate pump mixes the concentrate needs to be repeated every 48-72 hours.
with water thus making
the dialysate of desired Hemofiltration
concentration. The The procedure of hemofiltration is somewhat similar to
dialysate is also hemodialysis but the principle involved is different. In
pumped to the dialyser hemofiltration, dialysate is not used. Solute movement
but from opposite end. with hemofiltration occurs by convection. When the blood
In the dialyser, blood flows through the dialyser, a positive hydrostatic pressure
and dialysate flow in drives water and solutes across the filter membrane. This
opposite direction filtrate is drained. The excess fluid that is drained (after
(counter current). This considering for required ultrafiltration) is replaced by an
counter current isotonic replacement fluid. The advantage of
mechanism helps to hemofiltration is that convection overcomes the reduced
m a i n t a i n t h e removal rate of larger solutes (due to their slow speed of
concentration gradient diffusion) seen in hemodialysis. Thus clearance of
along the whole length Fig 2: Hemodialysis Machine phosphate, many uremic toxins such as complement factor
of the dialyser. D, leptin, erythropoiesis inhibitors is increased.
When hemofiltration is combined with hemodialysis, the
The dialysate pump also has adjustable flow rate and it is process is known as hemodiafiltration.
typically kept in the range of 500-800 mL/min.
In the dialyser, blood is pumped through the bundle of Slow Continuous Therapies
very thin capillary like tubes and the dialysate is pumped Slow Continuous Therapies are used for hemodynamically
unstable, fluid overloaded, catabolic septic
patients. These patients are generally having
AKI or multi organ failure. The following types
of slow continuous therapies are popular.

Sustained Low-efficiency Dialysis (SLED)

In SLED, standard HD equipment is used with
reduced dialysate and blood flow rates. The
blood flow rate is kept at 100-200 mL/min
while dialysate flow rate is kept at 100 ml/min.
The session is continued for 6-10 hours.

Continuous Renal Replacement Therapy

(CRRT)
There are many variations of CRRT. They are
categorized according to the access
characteristics and also according to the
modality chosen. In Arteriovenous (AV) an
Fig 3: Hemodialysis Procedure

Vol. 11, Issue 4, October 2012

arterial catheter allows blood to flow into the
extracorporeal circuit by the driving force of the systemic
blood pressure. The blood is returned by the venous
catheter. It does not require an extracorporeal blood
pump. But blood flow may be unreliable in hypotensive
patients. In Venovenous (VV) both catheters are placed in
veins. An extracorporeal blood pump is required to
circulate blood through the extracorporeal circuit.
Irrespective of the access, any of the three modalities viz
hemodialysis (HD), hemofiltration (H) or hemodiafiltration
(HDF) can be used. Thus the possible variations are
CAVHD, CAVH, CAVHDF, CVVHD, CVVH and CVVHDF.
The CRRT is continued continuously for more than 48hrs till
the filter clots.
Peritoneal Dialysis
The Peritoneal dialysis utilizes the peritoneum as the
dialyser. Peritoneal dialysis may be done acutely or
chronically with different types of catheter and machines
but the underlying basic principle is the same.
Principle
All types of peritoneal dialysis are performed by
introducing peritoneal dialysate in the peritoneal cavity.
This is achieved by inserting peritoneal dialysis catheter
which permits bi-directional flow of dialysate.
The most important principle for solute removal in PD is
diffusion, for which the driving force is the concentration
gradient between the blood and the dialysis fluid. Small
solutes move quickly through the membrane creating an
equilibrium during the dwell period. Larger solutes move
slowly across the peritoneum, reaching equilibrium point
takes a long time. Fluid removal in PD is by osmosis.
Both solute and fluid removal in PD is controlled by:
1. Glucose concentration of the dialysate
2. Dwell time of the dialysate
3. Volume of the dialysate
4. Peritoneal membrane characteristics
Types of Peritoneal Dialysis
Acute Peritoneal Dialysis
It is done for acute kidney injury. For acute peritoneal
dialysis, a short term, hard PVC catheter is used. Before
insertion, patient's bladder is emptied to prevent
Vol. 11, Issue 4, October 2012
accidental puncture. The catheter is inserted by puncturing
the abdominal wall about 2.5 cm below the umbilicus in
the midline. Through the catheter, the dialysate of 1-2 L is
introduced over a 10 minute period (inflow time). The
dialysate remains in the cavity for around 30 minutes
(dwell time) after which it is allowed to drain over a 20
minute period (outflow time). The cycles are then
repeated. During acute PD, it is essential to monitor
electrolytes particularly Na and K. Potassium is generally
required to be supplemented after 4-8 cycles. The cycles
can be continued for 48-72 hrs after which risk of
peritonitis increases considerably.
Long-term Peritoneal Dialysis
It is prescribed to CKD patients. It is of two main types:
Continuous Ambulatory Peritoneal Dialysis (CAPD) and
Continuous Cycling Peritoneal Dialysis (CCPD).
The catheters inserted in both remain for many years and
are softer and flexible. The double cuff straight Tenckhoff
catheter, a silicone catheter, is the most commonly used
catheter. The distal (intraabdominal) segment of the
catheter is positioned freely in the intraabdominal pelvic
area. The catheter's midportion is implanted within the
wall of the abdomen via one to two Dacron velour cuffs.
The deep cuff is embedded in the abdominal rectus
muscle. The superficial cuff in both double cuff and single
cuff catheters is placed subcutaneously approximately 2
cm from the catheter exit site on the abdominal wall.
Continuous Ambulatory Peritoneal Dialysis (CAPD)
CAPD involves manual exchange of dialysate (fig 4) and
Fig 4: CAPD Bag
doesn't require any machine. The patient may remain
ambulatory while the dialysate remains in the peritoneal
cavity. The fluid is allowed to stay in the abdomen for
several hours allowing excess fluid and toxins to move from
the blood to the dialysate. At the end of the dwell, the fluid
is drained by gravity into a collecting bag and the same
process is repeated. Draining dialysate and replacing it
with fresh solution takes about 30 minutes and is repeated
three to five times every day. The last exchange of the day
may be done before going to sleep, and the dialysate is
left in overnight.
Fig 5: APD Machine
Continuous Cycling Peritoneal Dialysis (CCPD) /
Automated Peritoneal Dialysis (APD) Conclusion
It uses a machine called a cycler (fig 5). A cycler circulates Dialysis is a unique modality that provides both short and
dialysate solution in and out of the peritoneal cavity at long term support for patient's survival in the absence of
evenly spaced intervals during the night for eight to 10 renal function. Type of dialysis chosen depends on various
hours. In the morning, peritoneal cavity is filled by factors such as residual renal function, co-morbidities,
dialysate that is carried in the peritoneal cavity during the hemodynamic stability, access to hospital services, work
day. During that time, patients do their daily activities. profile of the patient, physical environment and patient's
Before the patient goes to sleep, the catheter is desire. Except the transport characteristics of the
reattached to the cycler, the fluid is drained out and the peritoneum all other variables in all types of dialysis can
night exchanges are started. This cycle is repeated daily. be adjusted to achieve the desired response.

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Vol. 11, Issue 4, October 2012

 Kidney (Renal) Biopsy
Kidney biopsy is one of the key invasive
procedure to determine, the cause of
renal ailments specially nephrotic
syndrome and AKI. Traditionally metal
biopsy needle was used but now it has
been replaced by disposable biopsy
gun. Such performed by a trained
nephrologist under USG guidance, it is a
safe procedure and has very few
complications like hematoma, hematuria
etc.
A procedure done by biopsy - needle
(gun) by a competent physician / surgeon
where in strip of renal tissue is taken out
to be examined further by pathologists.
The needle biopsy is a specific entity as
opposed to surgical biopsy is which a
nephrectomised sample is provided for
biopsy.
The renal biopsy is done for arriving at a
diagnosis in various renal diseases and
also in classifying them. It helps in
prognosticating about the disease and
also guiding us in use of treatment
modalities.
Indications for Renal Biopsy
1. Nephrotic syndrome: In children
<1yrs and in Adolescents and adult
with N.S.
Also in steroids resistant nephrotics in
pediatric population
2. AKI : In patients with unexplained AKI
or when there is persistent active
urinary sediments or when renal
recovery is not happening in a
patient with suspected AKI.
3. Systemic disease with renal
dysfunction
Dr LK Jha a. D i a b e t e s w i t h a t y p i c a l
Sr Consultant Nephrologist presentations: (eg. with
Department of Nephrology microscopic hematuria, in patient
Pushpanjali Crosslay Hospital where retinopathy is absent, when
NCR-Delhi duration of diabetes is less than 4
yrs or, when fall in GFR is rapid).
b. SLE with lupus nephritis
c. Systemic vacuities' - suspected
Wegener's granulonatosis
polyangiitis, polyarteritis nodosa,
Vol. 11, Issue 4, October 2012
Dr LK Jha
good pasture's disease.
d. In patients with amyloidosis,
multiple myeloma or other
infiltrative disorders.
4. Unexplained CKD: in patients with
renal dysfunction of more than 3
months duration but with active
urinary sediments or normal sized
kidneys.
5. Subnephrotic proteinuma of >1gm /
day
6. Isolated hematuria – may identify
thin basement membrane disease /
Alport's / IgA nephropathy
7. Familiar renal disease: eg, FSGS,
Alport's disease
8. Renal transplant dysfunction: In a post
renal transplant setting to diagnose
acute and c hronic rejection,
recurrence of disease in transplant
kidney and drug (calcineurin
inhibitors) toxicities.
All patients have to undergo a
prebiopsy evaluation which includes:
blood pressure control) <160/95).
· Complete hemogram with platelets
· Coagulation profile including PT,
APTT, BT, CT
· USG to show that patient has two
normal sized and unobstructed
kidneys.
· Urine routine and C/S
· Check whether patient is on oral
anticoagulants or antiplatelets and
defer renal biopsy for 4-5 days.
Procedure of Kidney Disease
Typically it is done as bedside
procedure using ultrasound guidance
and automated biopsy needles.
A biopsy gun (automated needle) with
16G or 18G needle is used. For the
anxious patient, sedation may be
needed and informed consent is taken
from patient and relatives. An IV access
is secured and xylocaine sensitivity
testing is done before the procedure.
· The patient is allowed to lie prone
Table 1: Contraindications to renal biopsy
Contraindications of Percutaneous Approach
· Uncontrolled bleeding diathesis
a. Absolute: uncorrectable bleeding diathesis
· Large volume ascites
b. Relative contraindications: Hypertension, solitary
· Uncontrolled hypertension
kidney, multiple renal cysts, renal neoplasm, advanced · Morbid obesity
azotemia obesity, pyelonephritis kidney, uncooperative · Severe respiratory insufficiency
patient. Wherever possible above parameters should · Solitary kidney
be corrected before undertaking biopsy. · Failed percutaneous approach
patients with stable vitals may be discharged after day
with pillow under the abdomen to splint the kidneys. care admission.
· Ultrasound is used to localize the lower pole of kidney
preferably left kidney (as it is longer) and the site is Transjugular or transfemoral renal biopsy is rarely done
marked with pen. when a percutaneous approach is contraindicated. Other
· The skin is prepared and local anasethetic 2%, routes are open surgical renal biopsy and laparoscopic
xylocaine) is injected till the depth of the capsue of renal biopsy.
kidney. A help of lumber puncture needle (22-24G)
may be needed. Complications
· A small stab incision (2-3mm) followed by passage of In large series of renal biopsies
biopsy gun is made under USG guidance till capsule 1. Hematoma 3% - Clinically significant
of the kidney. 2. Gross hematuria 3%
· Patient is then told to take deep breath and hold 3. AV fistula formation 0.2% - by contrast enhanced
breath for 5-10 seconds and the automated needle is studies 15%
triggered on. The biopsy needle is withdrawn 4. Need of surgery < 0.1%
immediately. (nephrectomy) < 0.05%
· The above procedure is repeated – 2nd core is also 5. Death
taken from same site. 6 Biopsy of other organ by mistake
· The samples are sent to laboratories in different 7. Pneumothorax
preservatives for histopathology (formalin) for 8. Hemothorax
immunofluorescence (saline) and for 9. Page kidney - perirenal hematoma compressing upon
electronmicroscopy (glutargldehyde). kidney leading to renin mediated HTN
· If insufficient material is obtained further passes of
needle can be made.

Though above is the standard procedure, there may be

operator based accepted variations - like use of
ultrasound for location of the kidney and then performing
it without real time guidance.
· A CT guided procedure is also done in specific
circumstance.
· The biopsy is transplanted kidney is generally easier
as it is more superficial and generally immovable. The
general technique remains same.

Post Biopsy
Following the biopsy patient is rested in supine position for
at least 6-8 hrs.
· The staff is instructed to monitor vitals frequently and
notify any discrepancy.
· The patient is given separate containers of clear glass
for collecting urine for observing any gross hematuria.
· In the absence of hematuria patient is allowed to sit in
bed after 8 hrs and to gradually ambulate. Patient is
not allowed to sit or walk till hematuria is cleared.

Traditionally patients are kept overnight in hospital after

biopsy but lately after uncomplicated biopsy and

Vol. 11, Issue 4, October 2012

 Stem Cell Therapy in Nephrology
OL Kukharchuk, VV Radchenko, AB Padma Priya,
AO Kukharchuk and Pranav Anam
What are stem cells?
Stem cells have three main
characteristics. First – they are not
specialized cells (in contrary to cells of
muscles, brain, or heart). Second – stem
cells are capable to divide significantly
more number of times, than usual cells.
While dividing stem cells self-renews:
one among the 2 formed cells becomes
differentiated, and the second remains
the stem cell. The third important
characteristic of stem cells is their ability
after division to differentiate into
specialized cells, like muscle cells, brain
cells, blood cells and others. Cells of 1-
day embryo can differentiate into any of
240 types of cells. In adult organism
small amount of stem cells is present in all
organs, providing the reparation
(restoration) of injures and damaged
tissues. The younger the organism is the
bigger stem cell reserve is, and
accordingly body's restoration potential.
It is considered that application of stem
cells in medicine will give the possibility
to successfully combat diseases that are
regarded incurable today.
What is stem cell therapy?
Cell therapy (cell transplantation) is a
treatment with stem cells and tissues and
also with biologically active substances
they produce. Cell therapy is a branch of
modern medicine studying stem cells and
OL Kukharchuk
their clinical use. The main indication for
VV Radchenko
stem cell therapy is disease or condition
AB Padma Priya
resulting in cell count reduction. Stem cell
AO Kukharchuk treatments are a type of regenerative
Pranav Anam medicine that introduces new cells into
damaged tissue in order to treat a
disease or injury. Over 70 different
disorders have been identified as
amenable to stem cell therapy. The
Vol. 11, Issue 4, October 2012
process of treatment is to inject the
prepared stem cells into a patient to
repair specific tissues or to grow organs.
Can we treat renal diseases with stem
cells?
To decide the issue of possibility of using
stem cells in treatment of renal diseases,
at the foremost needed to answer the
question – do stem cells exist in the renal
tissue of the adult organism, which are
capable to differentiate into highly
specialized cells of the kidneys
structural-functional units – nephrons? If
stem cells exist in kidneys, this means that
in renal tissue occurs process of
physiological and reparative
regeneration on which we could
influence with the help of stem cells
transplantation. Recent results obtained
in humans. Suggest that the kidney
contains a “renopoietic system”, with a
progenitor localized at the urinary pole
of Bowman's capsule, from where it can
initiate the replacement and
regeneration of glomerular, as well as
tubular, epithelial cells (Fig. 1)1.
Thus, renal stem/progenitor cells might
contribute to tubular epithelium repair,
but this contribution probably occurs only
when a renal tubular injury cannot be
spontaneously repaired through the
migration of neighboring unwounded
tubular cells.
How the regeneration process changes
in renal diseases?
Most renal pathological conditions that
ultimately lead to end-stage renal
disease (ESRD), originate within the
glomerulus, and it has now been
established that depletion of podocytes,

the visceral epithelium of the capillary tuft, is central in
initiation of glomerulosclerosis, which is the common final
pathway of all glomerular diseases leading to ESRD. In
glomerular diseases such as diabetic nephropathy,
glomerulonephritis, or preeclampsia, significant numbers
of podocytes are lost as a result of apoptosis, necrosis, or
excretion of living cells into the urine. Unlike tubular cells,
podocytes are postmitotic cells that cannot undergo
complete cell division and are therefore unable to
regenerate themselves. Remission of disease and
regression of renal lesions are widely observed in
experimental animals and even in humans. However, the
repair of injured renal tissue in mammals is not sustained
by the generation of new nephrons and frequently leads
to a nonfunctioning mass of fibrotic tissue. In contrast,
early in gestation, injured fetal tissues can be completely
recreated, without fibrosis, in a process resembling
regeneration.
How does the adult kidney replenish cells lost through
damage or aging?
Recent results demonstrate that, during development,
mammalian nephrons derive from a single multipotent
progenitor that generates glomerular as well as tubular
epithelial cells and those cells with identical markers and
Vol. 11, Issue 4, October 2012
Fig 1: Series of schematic diagrams depicting the
morphological events and the localization of
CD24+CD133+ renal progenitors during the
different phases of nephron development1
Mesenchymal cells near the tips of the branching
ureteric bud are induced and differentiate
through a series of forms: aggregate (A), renal
vesicle (B), comma-shaped bodies (C), and S-
shaped bodies (D). Also shown is the developing
vasculature within the glomerular cleft of an S-
shaped body (E) and the glomerulus in a more
mature nephron (F). The tubular segments of the
mature nephrons empty into the collecting ducts
and eventually the ureter. Development proceeds
in a radial manner so that older nephrons are
centrally located and newer nephrons are added
at the periphery as indicated. Cells of the ureteric
bud are stained in green. CD24+CD133+ renal
progenitors are stained in red. (A):
CD24+CD133+ renal progenitors (red) localize
in the condensed mesenchyme but not in the
uninduced mesenchyme (white) or in the ureteric
bud (green). (B): CD24+CD133+ renal
progenitors localize in a primary vesicle but not in
the uninduced mesenchyme (white) or in the
ureteric bud (green). (C): CD24+CD133+ renal
progenitors localize in the comma bodies but not in
the uninduced mesenchyme (white) or in the
ureteric bud (green). (D): CD24+CD133+ renal
progenitors localize in the S-shaped body, in the
proximal loop, as well as in the distal loop, but not
in the uninduced mesenchyme (white) or in the
ureteric bud (green). (E): CD24+CD133+ renal
progenitors (red) localize in an S-shaped body
after colonization by primordial capillaries and
mesangium. (F): In maturing glomeruli,
CD24+CD133+ renal progenitors (red)
selectively persist as a subset of cells of the
Bowman's capsule localized opposite to the
vascular pole.
properties also exist in adult mammalian kidneys. Adult
renal progenitors are localized at the urinary pole of
Bowman's capsule, the only place of the nephron from
where they can initiate the replacement and regeneration
of glomerular, as well as tubular, epithelial cells. Thus,
converging evidence suggests that the kidney contains a
renopoietic system and that the urinary pole of Bowman's
capsule may represent a stem cell niche, which is a specific
site in adult tissues where stem cells reside2.
Which stem cells are needed to be used in renal
diseases and where must be introduced?
The question of which cell type is required is not a simple
one to answer for an organ such as the kidney, and the
answer may well vary depending on the renal disease.
The nexus between glomerular and tubular function and
disease is a close one, and it has been debated as to
whether nephron loss results from glomerular injury or
from tubule-interstitial responses. It has been argued that
the survival of a nephron after damage depends on the
ongoing health of the glomerulus, rather than the tubule
itself. This observation is consistent with the proposed
notion of Bowman's capsule progenitor cells2. What is
clear is that, whether replacement of cells within existing
nephrons or loss of those nephrons followed by interstitial
fibrosis, no new nephrons arise. In the case of
mesenc hymal stem cells, these cells are not
transdifferentiating but rather provide a reparative
cytokine/chemokine environment. The longevity of these
positive effects vs the potential for long-term damage
resulting from the aberrant differentiation of MSCs
remains unclear. If both of these concerns are allayed,
then the delivery of such “support cells” may prove a
viable treatment without the need for a renal stem cell. If
stem, renal, or non-renal cells are to be delivered into this
complex solid organ, then they will have to be injected into
the parenchyma or bloodstream. Delivery of cells through
the systemic circulation results in entrapment, particularly
within the pulmonary microvasculature. An active homing
mechanism may also be required for introduced cells to
preferentially reach the kidney. Some studies showed cells
introduced into the circulation do reach the kidney – either
by homing or passive transfer – and integrate into the
parenchyma3. Delivery of cells directly into the renal
parenchyma would deliver cells only into restricted
regions of the kidney.
Is it possible the renal structures to restore?
Even if these cells proliferated and integrated locally,
global organ-wide integration is unlikely. With a greater
understanding of normal cellular turnover within the
kidney, whether involving resident progenitor/stem cells
or an exogenous cell homing to the kidney, the more
feasible scenario may be to re-stimulate this response in
situ rather than have to deliver the cells themselves.
Current evidence supports a greater capacity for the
kidney to repair in response to damage than once
appreciated, including evidence for progenitors of
specific cell types; however, there is no evidence for one
Vol. 11, Issue 4, October 2012
master stem cell in the kidney that can recapitulate
development.
Could transplantation of mesenchymal stem cells
restore the renal function?
Transplantation of bone marrow mesenchymal stem cells
(BM-MSC) from rodents has been identified as a strategy
for renal repair in experimental models of acute kidney
injury (AKI), a highly life-threatening clinical setting. The
therapeutic potential of BM-MSC of human origin has not
been reported so far. Morigi M. et al. investigated
whether human BM-MSC treatment could prevent AKI
induced by cisplatin and prolong survival in an
immunodeficient mouse model. Results showed that human
BM-MSC infusion decreased proximal tubular epithelial
cell injury and ameliorated the deficit in renal function,
resulting in reduced recipient mortality. Infused BM-MSC
became localized predominantly in peritubular areas
and acted to reduce renal cell apoptosis and to increase
proliferation. BM-MSC also induced protection against
AKI-related peritubular capillary changes consisting of
endothelial cell abnormalities, leukocyte infiltration, and
low endothelial cell and lumen volume density as assessed
by morphometric analysis. These findings indicate that
human MSC of bone marrow origin hold potential to
prolong survival in AKI and should be considered for
testing in a clinical trial4.
The Kunter U et al study sought to determine whether
intrarenal injection of rat mesenchymal stem cells (MSC)
can preserve renal function in a progressive rat model of
glomerulonephritis (GN). Early in GN (day 10),
fluorescently labeled rat MSC localized to more than
70% of glomeruli, ameliorated acute renal failure, and
reduced glomerular adhesions. Fifty days later,
proteinuria had progressed in controls to 40±25 mg/d
but stayed low in MSC-treated rats (13±4 mg/d; P <
0.01). Renal function on day 60 in the MSC group was
better than in medium controls. Kidneys of the MSC group
as compared with controls on day 60 contained 11%
more glomeruli per 1-mm2 section of cortex but also
significantly more collagen types I, III, and IV and α-
smooth muscle actin. Approximately 20% of the glomeruli
of MSC-treated rats contained single or clusters of large
adipocytes with pronounced surrounding fibrosis.
Adipocytes exhibited fluorescence in their cytoplasm
and/or intracellular lipid droplets. Lipid composition in
these adipocytes in vivo mirrored that of MSC that
underwent adipogenic differentiation in vitro. Thus, in this
GN model, the early beneficial effect of MSC of
preserving damaged glomeruli and maintaining renal
function was offset by a long-term partial mal
differentiation of intraglomerular MSC into adipocytes
accompanied by glomerular sclerosis. These data suggest
that MSC treatment can be a valuable therapeutic
approach only if adipogenic mal differentiation is
prevented5.
Could transplantation of hematopoietic stem cells
restore renal function?
Li B et al studied the capacity of human CD34+
hematopoietic stem/progenitor cells (HSPCs) to promote
kidney repair and regeneration using an established
ischemia/reperfusion injury model in mice, with particular
focus on the microvasculature. Human HSPCs administered
systemically 24 hours after kidney injury were selectively
recruited to injured kidneys of immunodeficient mice and
localized prominently in and around vasculature. This
recruitment was associated with enhanced repair of the
kidney microvasculature, tubule epithelial cells, enhanced
functional recovery, and increased survival. HSPCs
recruited to kidney expressed markers consistent with
circulating endothelial progenitors and synthesized high
levels of pro-angiogenic cytokines, which promoted
proliferation of both endothelial and epithelial cells.
Although purified HSPCs acquired endothelial progenitor
marker since recruited to the kidney, engraftment of
human endothelial cells in the mouse capillary was an
extremely rare event, indicating that human stem cell
mediated renal repair is by paracrine mechanisms rather
than replacement of vasculature. These studies advance
human HSPCs as a promising therapeutic strategy for
promoting renal repair after injury6.
What are the clinical trials efficacy of stem cells have
been performed in humans?
Westenfelder Ch, Togel FE conveys about the results of
Phase I Clinical Trial, in which allogeneic MSCs were
administered to patients who were at high risk for open-
heart surgery-associated AKI. In this safety and feasibility
trial, adult subjects who have undergone on-pump
coronary artery bypass graft and/or cardiac valve
surgery were infused via the suprarenal aorta with
allogeneic MSCs, using a dose-escalating protocol. All
studied subjects presented with the following risk factors
for post-cardiac surgery-associated AKI: under lying
chronic kidney disease-1 to 4, congestive heart failure,
diabetes mellitus, hypertension, chronic obstructive
Vol. 11, Issue 4, October 2012
pulmonary disease, and age 65 years. Preliminary
analysis of the outcomes in this cohort of study subjects
showed that the suprarenal, postoperative administration
of allogeneic MSCs is feasible and safe, as it has not
resulted in adverse or serious adverse events, and
preliminary efficacy data appear promising, showing,
compared with well-matched historical case controls from
the same institution, that MSC therapy prevented
postoperative deterioration in renal function, reduced
length of stay, need for readmission, and prevented late
deterioration in renal function7.
Could it be effective stem cells transplantation in
chronic kidney disease?
End-stage renal disease is defined as the inability of the
kidneys to remove waste products and excess fluid from
the blood. ESRD progresses from earlier stages of chronic
kidney disease (CKD) and occurs when the glomerular
filtration rate is below 15 ml/minute/1.73 m2. CKD and
ESRD are dramatically rising due to increasing aging
population, population demographics, and the growing
rate of diabetes and hypertension. Identification of
multipotential stem/progenitor populations in mammalian
tissues is important for therapeutic applications and for
understanding developmental processes and tissue
homeostasis. Progenitor populations are ideal targets for
gene therapy, cell transplantation, and tissue engineering.
The demand for kidney progenitors is increasing due to
severe short age of donor organs. Because dialysis and
transplantation are currently the only successful therapies
for ESRD, cell therapy offers an alternative approach for
kidney diseases. However, this approach may be relevant
only in earlier stages of CKD, when kidney function and
histology are still preserved, allowing for the integration
of cells and/or for their paracrine effects, but not when
small and fibrotic end-stage kidneys develop. Although
blood- and bone marrow-derived stem cells hold a
therapeutic promise, they are devoid of nephrogenic
potential, emphasizing the need to seek kidney stem cells
beyond known extra renal sources. Moreover,
controversies regarding the existence of a true adult
kidney stem cell highlight the importance of studying cell-
based therapies using pluripotent cells, progenitor cells
from fetal kidney, or dedifferentiated/reprogrammed
adult kidney cells8.
Could fetal stem cells transplantation restore function
of kidney?
As nephrogenesis progresses the relative proportion of
the nephrogenic zone decreases. However, due to the fact
that stem cells are present in the fetal kidney until
relatively late in gestation term, can be exploited for their
isolation, making the fetal kidney an attractive source for
isolation and utilization of tissue-specific stem cells.
Encouraging results regarding the use of cells from
developing kidneys came from a report demonstrating
that transplantation of a heterogeneous population of
dissociated E14.5 and E17.5 rat fetal kidney cells under
the kidney capsule lead to the creation of renal structures,
and had beneficial effects on kidney function in a 5/6
nephrectomy model of kidney injury9. Also showed that
similarly to whole organ transplants, the gestational age
of cells to be transplanted has to be chosen carefully, as
early fetal kidney (E14.5) cells differentiated to non-
renal tissues, whereas cells from later gestational stages
showed poor ability to form kidney structures. Kim et al10
recently showed that E17.5 rat fetal kidney cells were
able to reconstitute kidney tissues only when cultured
through passage one, whereas P2 cells experienced
proliferation arrest and apoptosis, leading to poor
regenerative potential in vivo.

Do results exist on treating renal diseases in humans

with the help of fetal stem cells?
Tissues of fetal kidney consists all cellular elements in
developmental stages, which has potential to replace
damaged (injured) renal structures in adults (Fig. 2)2.
Results of the clinical trials, performed in Ukraine,
Fig 2: Stem cells in fetal kidney2
evidences that in cases of sustaining not less than 50% of
renal parenchyme the transplantation of fetal stem cells, From 12-13 and till 18-20 weeks of human gestation:
performed on the background of hemodialysis, in chronic (a–b) localization of SIX2 to the MM, predominantly to the
renal insufficiency reduces the level of creatinine in blood CM.
(c–d) shaped bodies and renal stroma.
plasma, increases glomerular filtration, normalize the (e–f) nephrogenic zone and newly forming tubules.
capability of kidney to concentrate urea. In 63% of (g–h) nephrogenic cortex, parietal epithelium of fetal
patients renal functions restores, that allows to eliminate glomeruli.
(i–j) some differentiated tubules.
from further hemodialysis (Fig. 3).

Conclusion
Until recently, basic paradigm of nephrology was that
kidneys are not capable to regenerate, but restoration
function of kidney occurs exclusively due to hypertrophy
of undamaged nephrons. Today we are aware that renal
tissues are like neural cells, restores due to division of
adult stem cells which are located in renal parenchyme.
These cells could be stimulated for division and
differentiation by introducing mesenchymal or
hematopoietic stem cells to patient. Therefore, the most
effective treatment of nephrological diseases could be
the stem/progenitor cells of fetal kidney. Fig 3: Dynamic of kidney function after SCT

Vol. 11, Issue 4, October 2012

 Nutrition in Renal Failure
A high prevalence of malnutrition exists
in patients with renal failure. Several
surveys have reported protein-calorie
malnutrition in up to 40% of this patient
population(1,2). Malnutrition in renal
failure is multifactorial, but surveys
consistently report inadequate oral
intake as a major contributing factor (1, 2).
Indicators of nutrition status including
reduced nutrient intake and muscle mass
are each independently associated with
increased 12-month mortality ( 2 ) .
Gastrointestinal complaints are
frequently seen in this patient population
and likely contribute to decreased intake
and malnutrition(3–5). Research suggests
that addressing GI issues in patients with
renal failure may improve nutritional
status ( 5 ) .Although the traditional
surrogate markers of malnutrition, such
as decreased muscle mass or serum
proteins have been associated with
increased mortality, research is ongoing
to determine if improving nutritional
status will alter patient outcomes.
Decreased muscle mass or serum proteins
can also be attributed to activation of the
acute-phase response related to co-
morbid conditions. However, there are
several studies that demonstrate that the
provision of increased nutrition to
patients with malnutrition and renal
failure may improve patient outcomes (1, 6).
Mrs Charu Dua
Overzealous diet restrictions can also
HOD – Dietetics,
contribute to decreased intake. The
Nutrition & F&B
provision of a “renal diet” that limits
Pushpanjali Crosslay Hospital
protein, salt, potassium, phosphorus and
NCR-Delhi
fluid may further limit intake in a patient
with existing malnutrition and poor oral
intake. Dietary intervention should not be
instituted until nutritional status and
December 2012
Charu Dua
eating habits have been investigated,
and the patient demonstrates a clear
need for dietary restriction.
Moreover Indian scenario is totally
different than American scenario,
where protein restriction needs to be
imposed. Most of the Indian who are
vegetarian do eat anywhere between
0.6gm – 0.8 gms of protein/ Kg
Bodyweight. If this population is
asked further to reduce protein in diet it
will gradually push them towards
malnutrition. Most of the CKD patients
seen in dietary OPD/IPD are almost on
negligible protein diets, which push
them closer towards malnutrition.
Furthermore, underlying causes for
electrolyte abnormalities such as poor
glucose control, use of potassium
c o n t a i n i n g s a l t - s u b s t i t u t e s, o r
medications as a cause of hyperkalemia
should be addressed before imposing
diet restrictions.
This article is written with an intention
that will empower the patients and
physicians to make better choices.
Nutrition in Chronic Kidney Failure
(CKD) for adults
Healthy kidney takes out the waste
products and extra minerals from foods
eaten. They maintain
· Sodium and water balance
· Support normal bone health by
balancing calcium and phosphorous
When your kidneys are not working
properly, they cannot get rid of waste
products and extra fluids. CKD usually
takes a long time to develop and does
not go away. In CKD, the kidneys continue to work — just
not as well as they should. Wastes may build up so
gradually that the body becomes used to having those
wastes in the blood. Minerals in food such as potassium,
sodium and phosphorous accumulate in your body and put
the heart, bones, lungs and general health at risk.
Generally people are at risk for developing CKD because
they have diabetes, high blood pressure, or both. High
blood glucose levels put people with diabetes at risk for
heart disease, stroke, amputation, and eye and kidney
problems. People with high blood pressure are at risk for
damaged blood vessels, including tiny vessels in the
kidneys.
The goal of diet is to focus on
· Preventing the excess accumulation of fluids and
wastes, while allowing the kidney to heal.
· To control and maintain blood glucose levels
· To control blood pressure
· To regulate your intake of Proteins, Potassium,
Phosphorous, Sodium (salt), Calcium, Fluid Intake.
Do's and Don'ts of Diet
1) Proteins: Protein is an essential part of any diet.
Proteins help build and maintain muscle, bone, skin,
connective tissue, internal organs, and blood. They help
fight disease and heal wounds. But proteins also break
down into waste products that must be cleaned from the
blood by the kidneys. Eating more protein than your body
needs may put an extra burden on the kidneys and cause
kidney function to decline faster.
Doctors have long recommended that patients with CKD
eat moderate or reduced amounts of protein.
Some patients, however restrict or totally avoid proteins
that leads to malnutrition( body is using muscle for energy)
Indian population is mostly vegetarian, and is already on
a low protein diet, before reducing protein in your diet
seek advice of a dietician the recommended amount of
protein intake should be 0.8gms/KG/BW. So if you ways
60kgs you should take atleast 48gms of protein in your
diet. Also it is important to take high biological value
quality proteins (good quality protein like milk, paneer,
egg, soya, chicken, fish etc). Though theses protein
increase the urea levels a balance of both good quality
and bad quality protein (dals, rice, wheat etc) is important
to maintain. Know the protein values
December 2012
Food Item Protein Content (gms)
Milk ( 250ml) 8 gms
Curd ( 100gms) 4.2 gms
Paneer ( 40gms) 10gms
Egg White 5 – 6 gms
Chicken/ Fish (50gms) 12 – 13 gms
Dals/ Besan/ Sprouts/ Soya 7 gms
( 1 Medium Size Katorie,
30 gms raw)
Seek help of a dietician to know how protein is good for
you, and how you can balance the intake and taste, while
helping kidneys to heal.
2) Potassium: is primarily present in vegetables and fruits,
Salads, Fruit Juices , soups, lime, Coconut water, Dried fruits
, nuts, tomato chutney, coconut Chutney etc If it begins to
climb (check vis blood test), talk with your dietitian about
ways to limit the amount of potassium you eat. You may
need to avoid some fruits and vegetables. You can reduce
the potassium content of food by following the tips below:
a. Dialyzing potatoes and other vegetables - you can
remove some of the potassium from potatoes and
other vegetables by peeling them, then soaking them
in large amount of water for several hours before use.
b. Drain and rinse well before cooking
c. Cooking all the vegetables helps removing some
potassium. Hence you may use tomatoes while
cooking, avoid them raw. Remember food has to be
tasty as your disease is making you anorexic (feeling
less hungry)
d. Avoid taking too much raw salad.
e. Limiting potassium content by portion control (the
amount of a food that you eat at one time) for e.g. a
high potassium tomato (1 small) provides 273 mg of
potassium. If you cut a thin slice to accent your
sandwich it provides much less; 1/6th of 1 small
tomato provides 45 mg of potassium.
f. Food Rich in potassium are Bananas, Oranges, melons,
excess tomatoes, raw vegetables, lemon, alma ,
vegetable soups, mushrooms, arbi, kathal chutneys
coconut water, fruit / vegetable juices etc.
g. Fruits that are low in potassium are apples,
pineapple, papaya, guava. Still remember not to
take more 100gms a day even if your potassium are
normal seek help of a dietician to know more.
3) Sodium: Sodium is found in ordinary table salt and
many salty seasonings like soy sauce etc. Canned foods,
some frozen foods, and most processed foods have large
amounts of table salt. Snack foods like chips and namkeens
are also high in salt. Too much sodium in your diet can be
harmful because it causes your blood to hold fluid. The
extra fluid raises your blood pressure and puts a strain on
your heart and kidneys. Talk with your dietitian about ways
to reduce the amount of sodium in your diet.
· Look for the sodium content on the nutrition labels of
the foods you buy. Choose "sodium-free" or "low-
sodium" food products. Aim to keep your daily
sodium intake less than 1,500 milligrams.
· Try alternative seasonings like imli juice, salt-free
seasoning mixes, or herbs like ( oregano, basil,
thyme, roasted zeera, black pepper )
· Avoid salt shaker on the table, chaat masala, metha
soda, aji-no-motto (MSG)
4) Phosphorus: is a mineral found in many foods. Too much
phosphorus in your blood pulls calcium from your bones.
Losing calcium will make your bones weak and likely to
break. Too much phosphorus may also make your skin itch.
Foods like milk and cheese, dried beans, peas, colas,
canned iced teas and lemonade, nuts, few chocolates and
peanut butter are high in phosphorus. Talk with your
dietitian about how much phosphorus you should have in
your diet. As your kidney disease progresses, you may
need to take a phosphate binder(your doctor may
prescribe) These medications act like sponges to soak up,
or bind, phosphorus while it is in the stomach. Because it is
bound, the phosphorus does not get into the blood. Instead,
it is passed out of the body in the stool.
5) Water: As your kidney disease progresses, you may
need to limit how much you drink because your kidneys
cannot remove the extra fluid, so it builds up in your body
and strains the heart. Tell your doctor if you notice you are
making either less urine or more urine or if you have any
swelling around your eyes or in your legs, arms, or
abdomen. If your doctor has asked you to reduce fluid/
water intake then follow the below
· Drink water as per thirst, don't take in excess. Drink sip
by sip do not gulp
· You can keep fluids down by drinking in small cups or
glasses.
· Freeze juices in an ice cube tray and eat it like a candy
or a bar.
· Plan one day of your fluid serving at every meal
· Any food that is liquid at room temperature also
December 2012
contains water. These foods include tea, coffee, soups,
melons, grapes, oranges, tomatoes, dals curd, milk,
lassi, jelly lettuce and celery. All these foods add to
your fluid intake.
6) Diabetes and Kidney Disease:
· Eat 5 -6 small Frequent Meal
· Do Not Skip Meals. Keep day to day intake consistent
so that the medication regime matches the food
intake Eat meals and snacks at the same time each
day to prevent high/low blood sugar levels.
· Use snacks to prevent severe hypoglycemia. Be sure
to have a bedtime snack containing protein, starch,
fat to provide the body with an energy source that
will last through the night.
· Manage carbohydrate intake carefully since the
amount of carbohydrate eaten, the time it was eaten
and what it was eaten with determines the blood
sugar level.
· Avoid over- treating low blood sugar by eating
enough carbohydrates to raise blood sugar.
Checking blood sugar every 10mins will help
determine how much to eat.
· Reduce cholesterol and saturated fat intake: reduce
total fat and trans fatty acid intake
· Maintain appropriate weight for height: avoid
becoming overweight.
· Increase fiber intake (Salads, Sprouts, vegetables,
fruits, brown bread, oats etc)
· Avoid foods high in salt ( Processed food, canned
food, market butter, ketchups, sauces, salt shaker etc)
· Avoid excessive protein intake by eating less red
meat.
· Avoid Eating Sugar and Its products
· Avoid eating fruits with Main Meals, eat them in
between. Avoid fruits like mango, banana, cheeku,
grapes if your sugars are high. Avoid fruit juices (
fresh or tetra pack)
· Avoid eating vegetables like potatoes, arbi, sweet
potato
7) Hypertension and Kidney Disease:
High Blood Pressure (hypertension) is a strong risk factor
for heart disease, stroke and kidney failure. Most patients
with established hypertension do not make sufficient
life–style changes, do not take medicines and neglect
their disease. Therefore to prevent and control
hypertension one needs to undergo lifestyle modification.
Lifestyle modification not only improves control but also
helps to reduce medication doses in hypertension.
Moreover, they help in preventing high blood pressure.
Lifestyle Modifications for Hypertension Prevention
and Management
Here are some tips on healthy living and lifestyle
modifications that would be helpful to everyone in the
family along with the person with high blood pressure. So
these should be adopted by all and no separate cooking
for the patient.
· Lose weight if overweight – Eat to live, do not live to
Eat.
· Regular Physical Activity – Wise depend on Exercise
for fitness.
· Reduce intake of dietary saturated fat - Clean up the
oily mess.
· Reduce salt (sodium) intake – Excess Salt is harmful.
· Maintain adequate intake of dietary potassium –
Diet rich in fruits and vegetables.
· Limit intake of alcohol – There is a Devil in Every Berry
of Grape.
· High dietary fiber intake – He who follows nature is
never out of the way.
· Avoid smoking and intake of excess caffeine – Don't
get reduced to ashes.
Nutrition during dialysis
When you start dialysis, you must make many changes in
your life. Watching the foods you eat will make you
healthier. Food gives you energy and helps your body
repair itself. Food is broken down in your stomach and
intestines. Your blood picks up nutrients from the digested
food and carries them to all your body cells. These cells
take nutrients from your blood and put waste products
back into the bloodstream. When your kidneys were
healthy, they worked around the clock to remove wastes
from your blood. The wastes left your body when you
urinated. Other wastes are removed in bowel movements.
Now that your kidneys have stopped working, dialysis
removes wastes from your blood. But between dialysis
sessions, wastes can build up in your blood and make you
sick. You can reduce the amount of wastes by watching
what you eat and drink. A good meal plan can improve
your dialysis and your health.
1. Fluids: You continue to restrict fluid as advised by
your doctor/ dietician. Fluid can build up between
December 2012
dialysis sessions, causing swelling and weight gain.
The extra fluid affects your blood pressure and can
make your heart work harder. You could have serious
heart trouble from overloading your system with
fluid.
Control your thirst
· The best way to reduce fluid intake is to reduce
thirst caused by the salt you eat. Avoid salty foods
like chips etc. Choose low-sodium products.
· You can keep your fluids down by drinking from
smaller cups or glasses. The dietitian will be able
to give you other tips for managing your thirst.
Your dry weight is your weight after a dialysis session
when all of the extra fluid in your body has been
removed. If you let too much fluid build up between
sessions, it is harder to get down to your proper dry
weight. Your dry weight may change over a period
of 3 to 6 weeks. Talk with your doctor regularly
about what your dry weight should be.
2. Continue to restrict potassium/ Phosphorous. One
fruit during dialysis is still okay but do not take more.
Try not to take fruits with high water con tenet (
melons, oranges etc)
3. Protein: Before when you were not on dialysis, your
doctor may have told you to follow a low-protein
diet. Being on dialysis changes this. Most people on
dialysis are encouraged to eat as much high-quality
protein as they can. Protein helps you keep muscle
and repair tissue. The better nourished you are, the
healthier you will be. You will also have greater
resistance to infection and recover from surgery
more quickly. Your body breaks protein down into a
waste product called urea. If urea builds up in your
blood, it's a sign you have become very sick. Eating
mostly high-quality proteins is important because
they produce less waste than others. High-quality
proteins come from meat, fish, milk, poultry, and eggs
(especially egg whites). Seek help from Dietician to
know the amount of protein you can now have in your
diet.
4. Sodium: Sodium is found in salt and other foods.
Most canned foods and frozen foods contain large
amounts of sodium. Too much sodium makes you
thirsty. But if you drink more fluid, your heart has to
work harder to pump the fluid through your body.
Over time, this can cause high blood pressure and
congestive heart failure.
Try to eat fresh foods that are naturally low in sodium
Look for products labeled low sodium.
Talk with a dietitian about spices you can use to flavor
your food. The dietitian can help you find spice blends
without sodium.
References
1. Mehrotra R, Kopple JD. Nutritional management of
maintenance dialysis patients: why aren't we doing
better? Ann Rev Nutr,2001; 21: 343- 379.
2. Kopple JD. Pathophysiology of protein-energy
wasting in chronic renal failure. J Nutr, 1999;129(1S
Suppl):247S-251S.
3. Strid H, Simren M, Stotzer P, et al. Patients with
chronic renal failure have abnormal small intestinal
motility and a high prevalence of small intestinal
bacterial overgrowth. Digestion, 2003;67(3):129-
137.
4. Van Vlem B, Schoonjans R, Vanholder R, et al.
Delayed gastric emptying in dyspeptic chronic
hemodialysis patients. Am J Kidney Dis, 2000; 36( 5):
962- 968.
5. Ross EA, Koo LC. Improved nutrition after the
detection and treatment of occult gastroparesis in
nondiabetic dialysis patients. Am J Kidney Dis, 1998;
31(1): 62- 66.
6. Capelli JP, Kushner H, Camiscioli TC, Chen SM, Torres
MA. Effect of intradialytic parenteral nutrition on
mortality rates in endstage renal disease care. Am J
Kidney Dis, 1994; 23(6): 808- 816.
Tel: +91-11-22148989, 22158989, Telefax: +91-11-22168989
Mobile: +91-9899499908, 9999432255, 9810003694, 9810454925
E-mail: anand@anandsurgicals.com, Website: www.anandsurgicals.com
December 2012
7. Mehrotra R, Kopple JD, Wolfson M. Metabolic
acidosis in maintenance dialysis patients: clinical
considerations. Kidney Int Supp,2003;( 88): S13-
S25.
8. Mitch WE, Price SR. Mechanisms activating
proteolysis to cause muscle atrophy in catabolic
conditions. J Ren Nutr, 2003; 13( 2):149- 152.
9. Natl. Kidney Found. I Init. K-DOQ. Clinical practice
guidelines for nutrition in chronic renal failure. Am J
Kidney Dis, 2000; 35:S1-S140.
10. Bergstrom J, Furst P, Alvestrand A, et al. Protein and
energy intake, nitrogen balance, and nitrogen
losses in patients treated with continuous
ambulatory peritoneal dialysis. Kidney Int,
1993;44: 1048- 1057.
11. Walser M, Mitch WE, Maroni BJ, Kopple JD. Should
protein intake be restricted in predialysis patients?
Kidney Int,1999; 55( 3): 771- 777.
12. Ikizler TA, Pupim LB, Brouillette JR, et al.
Hemodialysis stimulates muscle and whole body
protein loss and alters substrate oxidation. Am J
Physiol Endocrinol Metab, 2002; 282:E107-E116.
13. Scheinkestel CD, Kar L, Marshall K, Bailey M,
Davies A, NyulasiI, Tuxen DV. Prospective
randomized trial to assess caloric andprotein
needs of critically ill, anuric, ventilated patients
requiring continuous renal replacement therapy.
Nutrition, 2003; 19(11-12): 909- 16.

Dr Vibhu V Mittal
Consultant Gastroenterologist
Department of Gastroenterology
Pushpanjali Crosslay Hospital
NCR-Delhi
Vol. 11, Issue 4, October 2012
Mildly Elevated Transaminases (ALT, AST) :
Why And What To Do
Abstract
Mildly elevated transaminase is seen in
upto 1-9% of population. It signifies
ongoing liver injury. There are varied
common and uncommon hepatic and
extrahepatic causes for this. Evidence
regarding the corect approach of
evaluation is limited and the expert
consensus is for step based approach for
this problem. Detailed history and
examination is of paramount importance.
With the ease of doing liver function test
(LFT) due to availabilty of automated
machines, more and more such tests are
being asked for. In many such instances
the result is mildly elevated liver
enzymes. Mildly elevated liver enzymes
in a seemingly normal individual trouble
even an experienced physician.An
estimated 1% to 9% of people who have
no symptoms have high liver enzyme
levels when screened with standard
biochemistry panels.A US survey showed
elevated alanine aminotransferase (ALT)
in 8.9% of surveyed people from 1999
to 2002, an increase from previous
reports.
Significance of Transaminases
Both aspartate aminotransferase (AST)
and ALT are present in hepatocytes and
are released into the blood in greater
amounts when hepatocytes are
damaged. ALT is predominantly present
only in liver while AST is also seen in
myocyte and erythrocytes.Because of
this elevations in ALT are more specific
for liver injury. Normally these are
present in serum at low levels, usually less
than 30 to 40 U/L. Although the actual
values may differ from laboratory to
laboratory, normal serum levels are
usually less than 40 U/L for AST and less
than 50 U/L for ALT.
Dr Vibhu V Mittal
Some of the recent studies have pointed
the need to lower the values of "normal"
ALT to 19 U/L for male and 30 U/L for
female to increase the sensitivity of
diagnosing cases of mild hepatitis.
Though at these levels the specificity is
compromised with increase in number of
incidental abnormalities.
Anything below 5x (5 times upper limit
of normal) is considered as mildly
elevated. Persistant elevation has higher
significance.
Causes
Asymptomatic elevation of liver
transaminase levels can be categorized
into common hepatic, less common
hepatic, and extrahepatic causes. (Table
1).
Common Hepatic Causes
NASH - It is one of the leading cause of
mildly elevated liver enzymes in
asymptomatic individuals. Few of these
Table1: Causes of mildly raised
transaminases
Hepatic causes (Common)
• Non Alcoholic Steato Hepatitis (NASH)
• Alcohol
• Viral hepatitis
• Drugs and medication
Uncommon Hepatic causes
• Auto immune hepatitis
• Wilson's disease
• Hemochromatosis
• Alpha-1 Antitrypsin deficiency
Extra hepatic causes
• Celaic sprue
• Hemolysis
• Muscular disorder
• Thyroid disorder
Ref: Krier M, Ahmed A. Clin Liv Dis 2009
patients may progress to cirrhosis and HCC. It is common in
patients with diabetes mellitus, hypertriglyceridemia and
metabolic syndrome. Ultra sound, Computed tomography
and Magnetic resonance imaging have good sensitivity
and specificity to diagnose fat in liver but they cannot
differentiate it from alcohol related fatty liver.
Alcohol: It is an important etiology of deranged liver
enzyme which can be easily diagnosed with an accurate
history. Imaging or even liver biopsy cannot differentiate
alcoholic liver disease from NASH reliably. AST/ALT ratio
>1 and raised gamma glutamyl transferase levels
suggest the possibility of alcohol related liver disease.
Viral hepatitis: Hepatitis B and Hepatitis C are two
important treatable causes of liver disease. These cause
transient elevation of liver enzymes and testing is
recommended even if repeat levels are normal. They can
be diagnosed with HbsAg and Anti HCV tests respectively
Medications: Numerous medications have been
associated with elevated transaminase levels, but the true
incidence of liver injury from medications is unknown. Not
only the standard drugs but other xenobiotics including
herbal products are also an important cause and detailed
history evaluating the same is important. Eliciting all
over-the-counter and prescription medications and
stopping any potentially contributing agents may identify
the etiology.
Table 2: Hepatotoxicity of selected drugs
· Acetaminophen - acute hepatitis
· Allopurinol - granuloma
· Azathioprine - veno-occlusive disease, nodular
regenerative hyperplasia
· Diclofenac and other nonsteroidal anti-inflammatory
drugs
· Hydralazine -granuloma
· Isoniazid
· Methotrexate - fibrosis
· Methyldopa
· Nitrofurantoin - autoimmune-like disease
· Quinidine - granuloma
· Statins
· Amiodarone - phospholipidosis
· Corticosteroids
· Tetracycline
· Valproic acid
Ref: Navaro VJ et al. NEJM 2006
Vol. 11, Issue 4, October 2012
Uncommon Hepatic Causes
Autoimmune hepatitis : Relatively uncommon. More
common in females. Is also associated with other auto
immune phenomenon. Positive auto antibodies and raised
immunoglobulin G levels with typical biopsy findings are
diagnostic of AIH
Wilson's disease: It is an autosomal recessive genetic
disease of copper metabolism. The frequency of this is 1:
30000 in general population.Presence of Kayser Fleisher
(KF) ring on ophthalmological examination is suuggestive.
Diagnosis can be established with low cerruloplasmin
levels and high 24 hr urinary copper levels.
Studies of Mild Aminotransferase Elevations
Only a few studies have documented the results of a
thorough evaluation of patients with mildly elevated
aminotransferase levels. These various studies which
included detailed evaluation including liver biopsies
showed, that in patients in whom apparent diagnosis could
not be made after first and second line investigation;
NASH is the most common etiology in these cases
A large proportion of cases could not be diagnosed even
after liver biopsy
Compensated cirrhosis is diagnosed in significant
proportion of patients
But these studies were from an era prior to introduction of
serological testing of hepatitis C, moreover diagnosis of
NASH had inconsistencies in between various studies.
Approach to Patient
As is clear with previous discussion, the data dealing with
the issue is scarce and most is retrospective in nature. There
is also limited evidence on the most efficient evaluation of
asymptomatic patients with mildly elevated liver
transaminase levels, so present consensus is to adopt a
stepwise approach based on the prevalence of each
potential etiology.
Step 1 – History and Physical examination
Detailed history with emphasis on personal history of
alcohol consumption and drug history is paramount for
evaluation. Presence of chronic liver disease merit
expedited work up for cause and confirmation of cirrhosis.
History and examination looking for obesity and
metabolic syndrome may suggest possibility of NASH.
History of previous surgeries, blood transfusion, IV drug
abuse etc. may suggest possibilty of viral hepatitis. History
of other auto immune phenomenon in a lady may point
towards auto immune hepatitis and a family history of liver
disease especially pointing towards a autosomal recessive
inheritance pattern may suggest wilson's disease. Detailed
physical examination especially looking for evidence of
chronic liver disease (parotid swelling, loss of axillary hair,
gynaecomastia, palmar erythema, dupytren's contracture,
dilated abdominal veins,ascites or testicular atrophy)
should be done.
Even if there is no significant history or examination
findings, testing for Hepatitis B (HbsAg) and Hepatitis C
(Anti HCV) is recommended.
With all negative evaluation on history and physical
examination and negative viral markers, patient should
be kept in follow up with repeat measurement of ALT and
AST after a duration of 3-4 weeks. This is because in

Elevated ALT and AST

History and physical Examination

Discontinue hepatotoxic medication use, alcohol; repeat testing in 2-4 weeks

Persistent or unexplained ALT and AST abnormalities

HBsAg, Anti HCV

Fasting lipid profile, Blood sugar
USG abdomen

PT, albumin, complete blood count with platelet

Chronic liver disease Negative or consistent Abnormal

Or decompensation with non-alcoholic
Fatty liver disease
Further testing Workup

Lifestyle modification
Rx dyslipidemia DM

6 months

Resolve Persistent
Or
Improving
consider less common and extra hepatic cause
Observe
Positive or persistent >6months

Further testing – liver biopsy

Vol. 11, Issue 4, October 2012

many instances there may be a transient elevation of liver
enzymes due to a variety of identified or unidentified
factors such as inadverent drug ingestion or bystander
hepatitis due to systemic illness etc. This is based on clinical
evidence from a recent trial by Lazo M et al from a
European centre in which it was shown that more than 30%
of adults had normal enzyme levels on retesting after a
median of 17.5 d.
Step 2 – Rule out common causes
With negative initial evaluation and persistantly elevated
enzymes on repeat LFT, further evaluation is warranted. A
study conducted by National health and nutrition survey
had shown that Hepatitis B, Hepatitis C and
hemochromatosis were responsible for 31% of such cases.
However in India hemochromatosis is a rare disease and
only case reports are reported, as well the genetic
mutation responsible for it is much less than western data.
Non alcoholic steato hepatitis is the most common cause of
these enzyme elevation after common causes are
excluded. So next logical step is to order for USG
Abdomen to document for fatty liver and markers of fatty
liver like fasting blood glucosa and fasting lipid profile.
If there is concern about the p nossibility of chronic liver
disease, tests to evaluate synthetic function of liver such as
prothrombin time, S. Albumin with Albumin/Globulin ratio
along with complete blood count including platelet count
is recommended.
This Issue of
is Partly Sponsored by “Suprima”
A division of INTAS
Vol. 11, Issue 4, October 2012
Step 3 – Uncommon causes and liver biopsy
Six months of life style changes with treatment of any
identified cause is advocated. But if enzymes are
persistantly raised and worsening evaluation at an early
date may be undertaken. The evaluation would be to rule
out Auto immune hepatitis, Wilson's disease (if age <40
yr) and hemochromatosis. Extra hepatic causes could be
considered if clinical condition points towards it.Celiac
disease is an important treatable condition in this respect.
Similarly thyroid disorders can have deranged liver
enzymes with persistant derangement and negative
evaluation; liver biopsy may be indicated at 6 months.
References
1. Morisco F, Pagliaro L, Caporaso N, et al. University
of Naples Federico II, Italy. Consensus
recommendations for managing asymptomatic
persistent non-virus non-alcohol related elevation
of aminotransferase levels: suggestions for
diagnostic procedures and monitoring. Dig Liver Dis.
2008;40(7):585-598.
2. Krier M, Ahmed A. The asymptomatic outpatient
with abnormal liver function tests. Clin Liver Dis.
2009;13(2):167-177.
3. American Gastroenterological Association medical
position statement: evaluation of liver chemistry
tests. Gastroenterology. 2002;123(4):1364-1366.

Dr Anupam Chhabra
Incharge-Transfusion Medicine
Pushpanjali Crosslay Hopital
NCR-Delhi
December 2012
Blood Component Therapy
Introduction
Blood and blood components are
considered drugs because of their use in
treating diseases. As with drugs, adverse
effects may occur, necessitating careful
consideration of therapy. The transfusion
of blood cells is also transplantation, in
that the cells must survive and function
after transfusion in order to have a
therapeutic effect. The transfusion of red
blood cells (RBSs) is the best tolerated
form of transplantation, but it may cause
rejection. The rejection of platelets shown
as refractoriness to the platelet
transfusion is relatively common in
multiple transfused patients. Fresh Frozen
Plasma can be used to replace all
coagulation factors, so it especially
useful to treat multiple coagulation
deficiencies occurring in patients with
liver failure, DIC, vitamin K etc.
Cryoprecipitate contains factor VIII,
fibrinogen, von Wille brand factor
(vWF), and factor XIII, thus this product
can be used to correct deficiency of these
coagulation factors.
Each patient must be evaluated
individually to determine the proper
transfusion therapy, taking care to avoid
inappropriate over- or under-
transfusion. Transfusion decisions should
be based on clinical assessment andnot
on laboratory values alone.
Red blood cells
The decision to transfuse red blood cells
should be based on clinical assessment of
the patient and their response to any
previous transfusion as well as the
hemoglobin level. The function of a RBC
transfusion is to extend oxygen delivery
to tissues. Hemoglobin levels during
Anupam Chhabra
active bleeding are imprecise measures
of tissue oxygenation. Adequate or
inadequate fluid resuscitation can
significantly alter the measured
hemoglobin concentration. In addition, a
number of factors must be considered
besides the blood hemoglobin level such
as oxygenation in the lungs, blood flow,
hemoglobin, oxygen affinity and tissue
demands for oxygen. Consequently, the
adequacy of oxygen delivery must be
assessed in individual patients.
Dosage: A dose of one unit of
compatible Red Blood Cells will increase
the hemoglobin level in an average sized
adult who is not bleeding or hemolysing
by approximately 1 g/dL or Hct by 3%.
In neonates, a dose of 10-15 mL/kg
isgenerally given, packed red cells with
a hematocrit of approximately 60% will
increase the hemoglobin by about 3
g/dL.
Response: Unless the recipient is
bleeding or hemolysing, and provided
the transfused red cells are compatible,
the post-transfusion hemoglobin can be
accurately predicted from the patient’s
estimated blood volume, baseline red
cell volume and transfusion volume.
Transfused red cells have a half-life of
approximately 30 days in the absence
of other processes that would result in
red cell loss or premature removal.
Indications: Red blood cells are
indicated for patients with asymptomatic
deficiency of oxygen-carrying capacity
or tissue hypoxia due to an inadequate
circulating red cell mass. They are also
indicated for exchange transfusion (eg,
for hemolytic disease of the newborn)
and red cell exchange (eg, for acute chest syndrome in Table 2. Administration of Packed Red Blood Cells
sickle cell disease).
Recipient
1. Transfusion is rarely indicated when the hemoglobin
(Patient) A B O AB
level is above 10 g/dL and is almost always
indicated inpatients when the hemoglobin level is A 1st 2nd
below 6 g/dL; choice choice
2. The determination of transfusion in patients whose
B 1st 2nd Rh Rh
hemoglobin level is 6-10 g/dL should be based on choice choice Positive Negative
any ongoing indication of organ ischemia, the rate
and magnitude of any potential or actual bleeding, O 1st
choice
the patient’s intravascular volume status and risk of
complications due to inadequate oxygenation. AB 2nd 1st
3. Transfusion for patients on cardiopulmonary bypass choice choice

with hemoglobin level ≤6.0 g/dL is indicated. Rh 1st 2nd

Positive choice choice
4. Hemoglobin level ≤ 7.0 g/dL in patients >65 years
and patients with chronic cardiovascular or Rh 1st
respiratory diseases is indicated. Negative choice
5. For stable patients with hemoglobin level between 7
anesthesia
and 10 g/dL, the benefit of transfusion is unclear.
6. Transfusion is recommended for patients with acute • Aseptic necrosis of the hip or shoulder (unless
blood loss more than 1,500 mL or 30% of blood indicated for surgery)
volume. • Uncomplicated pregnancy
7. Evidence of rapid blood loss without immediate
control blood transfusion is indicated. Platelets
Platelets are also referred to as whole blood derived
Table 1. In Neonates and Critically Ill Children platelets, random donor platelets (RDP), random platelet
Maintain HCT between Clinical Status concentrates. Platelet pheresis is also referred to as single
donor platelets, or SDPs.
40-45% Severe cardiopulmonary
disease (e.g., mechanical RDP are derived from Whole Blood and should contain ≥
ventilation >0.35 FiO2) 5.5 x 10^10 platelets per bag in approximately 50-90
mL of plasma. SDP is obtained using automated cell
30-35% Moderate cardiopulmonary
disease (e.g. less intensive separators and should contain ≥3.0 x 10^11 plateletsper
assisted ventilation such as nasal
CPAP or supplemental oxygen) bag in >200 mL of plasma.

30-35% Major surgery Dosage:

20-30% Stable anemia, especially if To help prevent or treat bleeding, transfuse as needed to
unexplained breathing maintain target platelet count.
disorder or unexplained poor Prophylactic platelet transfusion in surgical patients:
growth
i. Rarely indicated when the platelet count is >100 x
Controversial indications include Leg ulcers, Pregnancy, 109 /l
“Silent” cerebral infarct and/or neurocognitive damage. ii. Usually indicated when the count is <50 x 109 /l
iii. With intermediate platelet counts (50-100 x 109 /l) -
Inappropriate Indications and Contraindications: based on the risk of bleeding
• Chronic, steady-state (asymptomatic anemia) Surgical and obstetric patients with micro vascular
• Uncomplicated pain episodes bleeding:
• Infection I. Usually require transfusion if the platelet count is
• Minor surgery that does not require general <50 x 109 /l

December 2012
Table 3: Current Prophylactic Platelet Transfusion Triggers Patients at risk for transfusion-associated graft-versus host
disease (TA-GVHD) should receive gamma irradiated
Patient Category Platelet Count
platelets. The dose of platelets is determined by the pre-
All Patient 10,000/µl transfusion platelet count, blood volume and the presence
or
of additional risk factors. A dose of one random donor unit
Stable patient 5000/µl
per 10 kg body weight may be used as a guide.
Patient with fever or recent 10,000/µl
hemorrhage (now stopped) Response: Post-transfusion platelet counts should be
Patient with Coagulopathy, 10,000/µl obtained between 10-60 minutes after infusion to asses
on heparin, or with anatomic transfusion recovery. Generally, expect an adult platelet
lesion likely to bleed count increment of approximately 7-10,000/mm3 for
ii. Rarely require therapy if it is >100 x 109 /l each RDP given, or 30-60,000/ mm3 for each SDP given.
iii. With intermediate platelet counts (50-100 x 109 /l)- In neonates and infants, a dose of 5-10 mL/kg of platelets
based on the patient's risk for more significant (RDP or SDP) should result in a 50-100,000/mm3
bleeding increment.
iv. Vaginal deliveries or operative procedures
ordinarily associated with insignificant blood loss Transfusion Refractoriness:
may be undertaken in patients with platelet counts a) To assess the platelet survival a postinfusioncounts at
24 hours should be performed (in non-immune factors
less than 50 x 109 /l
such as sepsis, splenomegaly, DIC, etc.)
v. Platelet transfusion may be indicated despite an
b) Alloimmune refractoriness may develop when at least
apparently adequate platelet count if there is
two consecutive poor platelet increments at 10-60
known platelet dysfunction and micro vascular
minutes after transfusion.
bleeding.
vi. When the platelet count cannot be done in a timely
Contraindications:
fashion in the presence of coagulopathy, platelets
1. Thrombotic thrombocytopenic purpura (TTP),
may be given when thrombocytopenia is suspected.
Idiopathic thrombocytopenic purpura (ITP), Heparin-
induced thrombocytopenia, unless life–threatening
Transfusion of Platelets
hemorrhage exists.
SDPs and RDPs should be ABO-identical with the recipient
2. There is no role for prophylactic platelet transfusion in
when possible.
routine primary open heart surgery unless there is:
Table 4. Administration of Platelets
Recipient's (Patient's) Donor (Blood Unit)

ABO STATUS 1ST CHOICE 2ND CHOICE 3RD CHOICE 4TH CHOICE

AB AB A* B* O*

A A AB B* O*

B B AB A* O*

O O A B AB

Recipient's Donor (Blood Unit)

Rh D Status Rh positive Rh negative Rh positive Rh negative

Rh positive 1st Choice 2nd Choice 1st Choice 2nd Choice

Rh negative 2nd Choice 1st Choice 2nd Choice 1st Choice

*In non-availability of group specific platelet concentrate, non-group specific platelet concentrate can be transfused after consultation.

December 2012
 i. Micro vascular bleeding and platelet count 4. Bleeding or prophylaxis of bleeding for a known
50,000/µl single coagulation factor deficiency for which no
ii. Microvascular bleeding (eg, post-operative chest concentrate is available.
tube drainage greater than 500 ml within 6 5. Thrombotic thrombocytopenic purpura.
hours) and non-diagnostic coagulation 6. Rare specific plasma protein deficiencies, such as C1-
abnormality. inhibitor.
3. Surgery or invasive procedure where platelet counts
is more than 50,000/µl, prophylactic platelet Contraindications:
transfusion is not indicated. 1. Increasing blood volume or albumin concentration
2. Coagulopathy that can be corrected with
Fresh frozen plasma
administration of Vitamin K.
Plasma consists of the non-cellular portion of blood that is
3. Normalizing abnormal coagulation screen results, in
separated and frozen after donation. It may be
the absence of bleeding.
prepared from whole blood or collected by apheresis.It
4. Hypovolaemia, plasma exchange procedures or
contains all coagulation factors.
treatment of immunodeficiency states.
Dosage: The amount of FFP needed depends on the
Cryoprecipitate
patient’s clotting factor levels, the levels needed to attain
Cryoprecipitate AHF is prepared by thawing FFP and and
a therapeutic result, whether or not the patient is bleeding,
recovering the precipitate. It contains factor VIII,
and the patient’s blood volume. If possible, coagulation
tests (ie, PT or INR and aPTT) should be performed before fibrinogen, vonWillebrand factor (vWF), and factor XIII.
the administration of FFP in a bleeding patient.
Dosage:
Indications: The number of cryoprecipitate units can be estimated
Fresh Frozen Plasma is indicated for use in patients with byusing the following calculation
the following conditions: 1. Weight (Kg) x 70mL/Kg = blood volume (mL)
1. Active bleeding due to deficiency of multiple 2. Blood volume (mL) x (1.0-hematocrit) = plasma
coagulation factors, or risk of bleeding due to volume(mL)
deficiency of multiple coagulation factors. 3. Fibrinogen required (mg) = (desired fibrinogen level
2. Severe bleeding due to warfarin therapy, or urgent (mg/dL) - initial fibrinogen level (mg/dL)) multiplied
reversal of warfarin effect by (plasma volume (mL) / 100).
3. Massive transfusion with coagulopathy and bleeding. 4. Bags of cryoprecpitate required = mg fibrinogen
required/ 250 mg fibrinogen per bag of cryo.
Table 5: Administration of Fresh Frozen Plasma
The frequency of dosing depends on the half-life and
Recipient Donor (Blood Unit) recovery of the coagulation factor that is being replaced
(Patient) A B O AB
(check factor levels).
st nd As a thumb rule - one cryoprecipitate unit per 7 - 10 kg of
A 1 2
choice choice body weight can be transfused.
Indications: Patients with fibrinogen deficiency where
B 1st 2nd there is clinical bleeding, an invasive procedure, trauma
choice choice
or disseminated intravascular coagulation .
O 2nd 3rd 1st 4th
choice choice choice choice
Administration of Cryoprecipitate
AB 1st Cryoprecipitate may not be ABO identical however ABO
choice
compatible cryoprecipitate is preferred. The
Note: Rh(D) positive plasma should not be given to Rh(D) compatibility testing is not necessary, Rh type need not be
negative women in the reproductive age group.
considered when using this component.

December 2012
Response: Pretransfusion and post-transfusion
coagulation factor levels should be determined to assess References
the adequacy of the cryoprecipitate dose. 1. Standards for Blood Banks/Bank Centers and
Transfusion Services, NABH.
Contraindications: This component is not generally 2. Transfusion Medicine Technical Manual Second
considered appropriate in the treatment of edition; Directorate General of Health Services,
i. hemophilia Ministry of health & Family Welfare, Govt. of India,
ii. von Will brand’s disease, or deficiencies of factor XIII New Delhi.
or fibronectin, unless alternative therapies are 3. Practice Guidelines for Blood Transfusion, second
unavailable. edition, American Red Cross.
4. Practice Guidelines for Perioperative Blood
Conclusions: Patients who require blood or blood
Transfusion and Adjuvant Therapies; ©2006
products, whether in life-threatening acute situations or as
American Society of Anesthesiologists, Inc.
a supportive therapy in chronic hematological disorders, Lippincott Williams & Wilkins, Inc.
must receive the required component only. Transfusion of
packed red blood cells should be used for situations in
which clear physiological indicators for transfusion are
present. Depending upon the condition and disease of the
patient prophylactic platelet transfusion trigger can be as
low as 10,000/µl. Before administration of FFP in a
bleeding patient coagulation profile should be obtained.
Fibrinogen concentration should be obtained before the
administration of cryoprecipitate in a bleeding patient.

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Dr Priya Gupta
Consultant Neurologist
Department of Neurology
Pushpanjali Crosslay Hopital
NCR-Delhi
Vol. 11, Issue 4, October 2012
An Approach to Headache
Introduction
Headache is one of the most common
symptoms in neurology and one of the
most common reasons patients seek
medical attention. Headache occurs due
to activation of pain-sensitive structures
in or around the brain, skull, face, sinuses,
or teeth. Headaches may occur as a
primary disorder or be secondary to
another disorder. The most important
task in evaluation of headache is to
determine whether a patient has a
primary or secondary headache, or a
potentially life-threatening cause of
headache.
Pathophysiology of Headache
Headache consists of pain or discomfort
arising from pain-sensitive structures in
the head. These include extracranial
structures such as the skin, muscles, and
blood vessels in the head and neck;
mucosa of the sinuses and dental
structures; and intracranial structures
including the regions of the large arteries
near the circle of Willis, the great
intracranial venous sinuses, parts of the
dura and dural arteries, and cranial
nerves. The cranium, brain parenchyma,
ependymal lining of the ventricles, and
choroid plexus are all pain insensitive.
Table 1. Pain Sensitivities of Structures in the head
Sensitive
Extracranial Skin, muscles, fascia
Blood vessels
Mucosa of sinuses
Dental structures
Intracranial Large arteries near circle of Willis
Large venous sinuses
Dural arteries and parts of dura
Dr Priya Gupta
A headache can be the result of a direct
irritation of, or traction on, pain-sensitive
intracranial or extracranial structures.
Inflammatory conditions such as
meningitis produce pain by direct
irritation of these structures. Mass lesions
including tumors and abscesses cause
pain by producing traction on these
structures, most commonly on dural
vessels or the arteries of the circle of
Willis. Factors that increase the pressure
produced by such lesions will increase
the intensity of pain. Headache
produced by this mechanism is worsened
by the increase in central venous
pressure caused by the Valsalva
maneuver. The patient will often note a
more severe headache on awakening,
which lessens somewhat after an upright
position has been maintained for a
period of time, due to a slight increase in
brain edema induced by periods of
recumbency.
Headache Classification
Currently, the most widely used system
for classifying headache is that of
International Headache Society, the
International Classification of Headache
Disorders, Second Edition. The ICHD-2 is
designed mainly for diagnostic
Insensitive
Skull (except periosteum)
Parenchyma of brain
Pia mater, arachnoid mater,
parts of duramater
Ependyma, choroid plexus
consistency for research purposes, but it is helpful in Table 3. Characteristics of Primary and Secondary
establishing the correct diagnosis which then guides headache
treatment. Part 1 of the ICHD-2 classifies primary Characters of Primary Headache
headache (ie, those with no other known cause) as 1 of 4 1. Recurrent attacks
main types. Secondary headaches are classified based 2. Symptoms free between the attacks
on aetiology, not on symptom profile. There are nine 3. Pain shift inside and location
categories of secondary headache (against eight in the 4. Clinical syndromes fulfill IHS* criteria
ICHD-1). 5. Physical examination normal
6. No organic causes
Table 2. The International Classification of Headache 7. Exception: drug-abuse headache
Disorders, 2nd edition
Characters of Secondary Headache
1. Progressive course
Part I: The Primary Headaches 2. Symptoms persist
1. Migraine 3. Pain select to anatomical lesions
2. Tension-type headache 4. Side-locked
3. Cluster headache and other trigeminal autonomic 5. Physical examination usually abnormal
cephalalgias
4. Other primary headaches
Table 4. Some Characteristics of Primary Headache
Part II: The Secondary Headaches disorders
1. Headache attributed to head and/or neck trauma
2. Headache attributed to cranial or cervical vascular Migraine Frequently unilateral and pulsating, lasting
disorder headache 4–72 h; occasionally with aura, nausea,
3. Headache attributed to non-vascular intracranial photophobia, or osmophobia
disorder Worse with activity, preference to lie in the
4. Headache attributed to a substance or its withdrawal dark, resolution with sleep
5. Headache attributed to infection
6. Headache attributed to disorder of homoeostasis Cluster Unilateral orbitotemporal attacks
7. Headache or facial pain attributed to disorder of headache at the same time of day
cranium, neck, eyes, ears, nose, sinuses, teeth, mouth or Deep, severe, lasting 30–180 min; often
other facial or cranial structures with lacrimation, facial flushing, or Horner's
8. Headache attributed to psychiatric disorder syndrome; restlessness
Part III: Cranial Neuralgias Central and Primary Facial Tension-type Frequent or continuous, mild, bilateral, and
Pain and Other Headaches headache viselike occipital or frontal pain that
1. Cranial neuralgias and central causes of facial pain spreads to entire head
2. Other headache, cranial neuralgia, central or primary Worse at end of day
facial pain

If a patient experiences a new kind of headache for the Evaluation of Headache

first time in close temporal relation to another disorder
known to cause headache and the headache is attributed
to that disorder, the headache should be coded as a
secondary headache. The headache is generally
considered to be secondary headache if it has at least
one of the following characteristics specified.
• The secondary disorder known to be able to cause
headache has been demonstrated.
• Headache occurs in close temporal relation to the
secondary disorder and/or there is other evidence of
a causal relationship.
• Headache is greatly reduced or disappears within 3
months (this may be shorter for some disorders) after
successful treatment or spontaneous remission of the
causative disorder. There are exceptions to this
general rule, for example chronic posttraumatic
headache does not disappear 3 months after the
trauma.
Vol. 11, Issue 4, October 2012
Evaluation focuses on determining whether a secondary
cause is present. If no cause is identified, it focuses on
diagnosing primary headache disorders. The vast
majority of headaches result from benign conditions, but
because the symptom can represent an early
manifestation of a potentially serious disorder, it
necessitates thorough evaluation.
· History
· Physical examination
o General physical examination
o Neurological examination
· Investigations
History
In most instances, a good clinical history is sufficient to
accurately diagnose a patient's headache and
determines whether additional laboratory testing or
neuroimaging is indicated on the basis of patient's
symptoms and signs.
Table 5: History to be taken in a case of Headache
Temporal Profile:
· Acute vs Chronic (gradual, sudden, sub acute)
· Time to maximal pain
· Frequency: For recurrent headaches, age at onset,
temporal pattern (including any relationship to phase of
menstrual cycle), and response to treatments (including
OTC treatments) are also noted.
Characteristics of Pain:
· Location and Radiation (diffuse, either unilateral or
bilateral, or localized)
· Duration (Intermittent, Constant )
· Quality ( Throbbing, stabbing, dull, other)
· Quantity (Intensity of pain)
Prodromal Symptoms:
· Patients with migraine may report visual symptoms such as
scintillations, scotoma, or hemianopsia, malaise or psychic
disturbances, rarely hemiplegia or ophthalmoplegia may
also occur.
Alleviating and Exacerbating factors:
· Valsalva acitivity: Causing onset of pain, think SAH;
increases pain think any cause of increase ICP
· Coital: may precipitate rupture of aneurysm, benign
orgasmic headache may also occur
· Supine is worse: sinusitis, cerbral venous thrombosis,
intracranial mass
· Supine is better: low pressure headaches
· Medications: nitrates and other vasodilators,
indomethacin, and oral contraceptives
· Foods such as alcohol or those containing tyramine or
sodium nitrates may precipitate vascular headaches
· Exercise, light, noise, etc
· Head trauma
Associated Symptoms:
· Nausea/Vomiting, Photophobia, Phonophobia may be
associated with Migraine
· Autonomic symptoms such as lacrimation, nasal
congestion, facial flushing, or Horner's syndrome
accompany cluster headaches
· Meningeal signs
· Neurological deficits
· Seizures
Medical History:
· Constitutional symptoms, HTN, DM, hyperlipidemia,
Smoking, Trauma
· Previous history of malignancy or systemic disease
· Family history should be investigated because migraine is
commonly familial
Physical Examination
The primary purpose of the physical examination is to
identify causes of secondary headaches. The examination
should target areas identified as abnormal during the
Vol. 11, Issue 4, October 2012
headache history. The general physical examination
should include vital signs, funduscopic and cardiovascular
assessment, and palpation of the head and neck. A
complete neurologic examination is essential, and the
findings must be documented.
Table 6: Physical examination
Vital signs:
· Temperature, Blood pressure
Headache and Neck examination:
· Scalp for swelling and tenderness
· Auscultation for bruits in H/N
· Temporal artery inspection and palpation
· Temporomandibular joints palpation for tenderness
and crepitance
Eyes and Periorbital area examination:
· Note any lacrimation, flushing, and conjunctival injection
· Intraocular pressure
· Oropharynx examination for swellings
· Neck is flexed to detect discomfort, stiffness, or both,
indicating meningismus
· Cervical spine is examined for tenderness or restriction of
movements
Neurological examination:
· Mental status and level of consciousness
· Cranial nerve testing with particular attention should be
given to detecting problems related to the optic,
oculomotor, trochlear and abducens nerves (pupillary
reflexes, visual acuity, visual fields, fundoscopy, extra
occular movements)
· Motor strength testing, deep tendon reflexes, sensation,
pathologic reflexes
· Cerebellar function and Gait testing
· Signs of meningeal irritation (Kernig's and Brudzinski's
signs)
Red Flags
Only a few headaches are secondary, but this category
contains the most life-threatening diagnoses. Although
prospective studies are lacking, several publications have
commented on historical and physical findings that are
considered red flags for serious problems based on
clinical experience. Currently, these findings offer the best
means of identifying a secondary headache disorder.
Focal neurologic findings should prompt additional
evaluation. Among others, these findings include
unilateral loss of sensation, unilateral weakness, unilateral
hyperreflexia and papilledema.
Table 7: Red flags: following findings are of Table 9: Indications of Neuroimaging CT (or MRI) in
particular concern a patient of headache
Red Flags
1. Thunderclap headache
· Neurologic symptoms or signs (eg, altered mental status,
2. Altered mental status
weakness, diplopia, papilledema, focal neurologic
deficits) 3. Meningismus
· Immunosuppression or cancer 4. Papilledema
· Meningismus 5. Signs of sepsis (eg, rash, shock)
· Onset of headache after age 50 6. Acute focal neurologic deficit
· Thunderclap headache (severe headache that peaks 7. Severe hypertension (eg, systolic > 220 mm Hg or
within a few seconds) diastolic > 120 mm Hg on consecutive readings)
· Symptoms of giant cell arteritis (eg, visual disturbances,
jaw claudication, fever, weight loss, temporal artery
tenderness, proximal myalgias) In addition, if meningitis, subarachnoid hemorrhage, or
· Systemic symptoms (eg, fever, weight loss) encephalitis is being considered, lumbar puncture and CSF
· Progressively worsening headache analysis should be done, if not contraindicated by imaging
· Red eye and halos around light results.
Tonometry should be done if findings suggest acute

Table 8: Matching Red Flag findings with a cause for Headache

Suggestive Findings Causes

Neurologic symptoms or signs (eg, altered Encephalitis, subdural hematoma, subarachnoid or

mental status, confusion, neurogenic intracerebral hemorrhage, tumor, other intracranial mass,
weakness, diplopia, papilledema, increased intracranial pressure
focal neurologic deficits)

Immunosuppression or cancer Brain infection, metastases

Meningismus Meningitis, subarachnoid hemorrhage, subdural empyema

Onset of headache after age 50 Increased risk of serious cause (eg, tumor, giant cell arteritis)

Thunderclap headache (severe headache Subarachnoid hemorrhage

that peaks within a few seconds)

Combination of fever, weight loss, visual Giant cell arteritis

disturbances, jaw claudication, temporal
artery tenderness, and proximal myalgias

Systemic symptoms (eg, fever, weight loss) Sepsis, thyrotoxicosis, cancer

Progressively worsening headache Secondary headache

Red eye and halos around lights Acute angle-closure glaucoma

Investigations narrow-angle glaucoma (eg, visual halos, nausea, corneal

Most patients can be diagnosed without testing. However, edema, shallow anterior chamber).
some serious disorders may require urgent or immediate
Other testing should be done within hours or days,
testing. Some patients require tests as soon as possible.
depending on the acuity and seriousness of findings and
should be done in patients with any of the following
suspected causes.
findings:

Vol. 11, Issue 4, October 2012

Table 10: Neuroimaging, usually MRI, should be
done if patients have any of the following:
· Focal neurologic deficit of subacute or uncertain
onset
· Age > 50 years
· Weight loss
· Cancer
· HIV infection or AIDS
· Change in an established headache pattern
· Diplopia
ESR should be done if patients have visual symptoms, jaw
or tongue claudication, temporal artery signs, or other
findings suggesting giant cell arteritis.
CT of the paranasal sinuses is done to rule out complicated
sinusitis if patients have a moderately severe systemic
illness (eg, high fever, dehydration, prostration,
tachycardia) and findings suggesting sinusitis (eg, frontal,
positional headache, epistaxis, purulent rhinorrhea).
Lumbar puncture and CSF analysis are done if headache
is progressive and findings suggest idiopathic intracranial
hypertension (eg, transient obscuration of vision, diplopia,
pulsatile intracranial tinnitus) or chronic meningitis (eg,
lethargy, vomiting, focal neurologic deficits).
Treatment
Most patients with a primary headache require
medication; however, other management methods also
may be useful. Secondary headaches usually resolve
when the underlying neurologic or systemic problem is
treated.
Primary headache
· Acute treatment
· Preventive treatment
- Medical treatment
- Non-medical treatment
Secondary headache
· Symptomatic treatment
· Specific treatment for causes
Key Point
· Recurrent headaches that starts at a young age in
patients with a normal examination are usually
benign.
· Immediate neuroimaging is recommended for patients
with altered mental status, seizures, papilledema,
focal neurologic deficits, or thunderclap headache.
· CSF analysis is required for patients with meningismus
a n d u s u a l l y, a f t e r n e u r o i m a g i n g , f o r
immunosuppressed patients.
· Patients with thunderclap headache require CSF
analysis, even if CT and examination findings are
normal.
Vol. 11, Issue 4, October 2012
Table 11: Treatment of primary headache
Migraine Acute attacks
headache · Oral analgesics ± Antiemetic
· Parenteral Analgesic ± Antiemetic
(Contraindications: Peptic ulcer or lower
bowel disease, Diarrhoea )
· Triptans (Contraindications: Uncontrolled
hypertension, Risk factors for CHD or CVD,
Children under 12 years)
· Ergotamine (Contraindications:
Ergotamine is not an option if triptans are
contraindicated and should not be taken
concomitantly with a triptan, Beta-blocker
therapy, not advised for children)
Preventive therapy:
· Betablockers- Beta-blockers (atenolol,
metoprolol, propranolol, bisoprolol) if
not contra-indicated
· Antidepressants- amitriptyline (when
migraine co-exists with TTH, Another
chronic pain condition, Disturbed sleep,
Depression)
· Anticonvulsants- sodium valproate,
topiramate
· Calcium channel antagonists - verapamil
Cluster Acute attacks:
headache · Subcutaneous sumatriptan 6 mg
· High dose/high flow rate oxygen
Preventive therapy: Ergotamines,
corticosteroids, verapamil
Tension-type Episodic form: NSAID drugs
headache Chronic therapy: Tricyclic antidepressants
References
1. American Academy of Neurology. Guideline summary for
clinicians: Migraine headache.
2. Headache Classification Subcommittee of the International
Headache Society. The international classification of headache
disorders. 2nd ed. Cephalalgia. 2004, 24: (Suppl 1): 1-160.
3. Silberstein SD. Practice parameter: Evidence-based guidelines
for migraine headache (an evidence-based review): Report of
the Quality Standards Subcommittee of the American Academy
of Neurology. Neurology. 2000, 55: 754-762.
4. Friedman AF. Headache. In: Baker AB, Baker LH, eds. Clinical
neurology. New York: Harper and Row, 1979;2:Chap 13.
5. Diamond S, Dalessio DJ. The practicing physician's approach to
headache, 3d ed. Baltimore: Williams and Wilkins, 1982.
6. Messlinger, K., and R. Burstein. (2000). Anatomy of central
nervous system pathways related to head pain. In The
Headaches, 2nd ed., (J. Olesen, P. Tfelt-Hansen, and K.M.A.
Welch, eds.), pp. 77 - 86. Lippincott Williams and Wilkins,
Philadelphia
7. Kaniecki R. Headache assessment and management. JAMA
2003; 289: 1430-33.
8. Steiner TJ, Fontebasso M. Headache. BMJ 2002; 325: 881-86.

Dr Kapil Kumar Singhal
Consultant Neurologist
Department of Neurology
Pushpanjali Crosslay Hospital
NCR-Delhi
Vol. 11, Issue 4, October 2012
Cerebral Venous Thrombosis: Not So Uncommon?
A 22 year old male presented to the
hospital with complaints of headache for
3-4 days. Headache was holocranial,
moderate to severe intensity, not
associated with nausea, vomiting,
blurring of vision and was not having any
specific aggravating or relieving factors.
After 3 days of headache, he had
abnormal sensation in the form of ant like
crawling sensation in his right hand which
subsided after few minutes. These
symptoms recurred a few times and on
the day of presentation to the hospital,
he had a seizure. It started with
abnormal sensation, followed by
abnormal movement of hand and face
and later generalization of seizure. He
did not have any previous history of
seizures. He did not have any post ictal
weakness. He was a smoker, but non
hypertensive and sugar levels were
never tested previously. No significant
medical illness was present in the family.
Clinical examination revealed a normal
systemic examination. Neurological
examination was unremarkable except
for early papilledema.
The patient was managed initially with
anti epileptic drugs and in view of
sensory phenomenon, a possibility of
focal seizure with right parietal
localization was considered.
A. Differential Diagnosis
The presentation can be summarized as
focal seizure, possible right parietal
localization and signs of raised intra
cranial pressure. This gentleman
does not have any risk factors, no
history of fever and no past history
Dr Kapil Kumar Singhal
of seizures. The possibilities which
should be considered include
1. Intracranial space occupying lesion
2. I n f l a m m a t o r y g ra n u l o m a s -
Neurocysticercosis, Tuberculomas
3. Focal encephalitis
4. Vascular etiologies: ischemic lesion,
focal parenchymal hemorrhages
5. Vascular malfor mations with
hemorrhages
6. Cerebral venous thrombosis
Neuroimaging was done on priority due
to presence of papilledema. (Fig 1-4)
MRI Brain revealed:
1. Diffusion weighted image shows tiny
focal area of restricted diffusion in
right posterior frontal lobe,
representing acute infarct.
2. Axial gradient FFE image shows
focal area of blooming in right
posterior frontal lobe, c o n s i s t e n t
with hemorrhage.
3. Axial post contrast image shows
filling defect in posterior aspect of
Fig 1: Fig 2:
Fig 3: Axial post Fig 4: MR Venography
contrast view
 superior sagittal sinus, consistent with venous
thrombosis.
5. MR venography showing diffuse partial filing defect in
superior sagittal sinus, confirming venous thrombosis.
B. How to further evaluate for the cause?
This patient presented with signs of raised intracranial
pressure and focal seizures. His MRI Brain revealed a small
hemorrhagic infarct in right parietal area which
corroborated with his seizure semiology. MR Venography
showed non visualization of superior sagittal sinus. This
confirms diagnosis of Cerebral Venous Thrombosis (CVT).
The does not have any apparent risk factors for
developing CVT. However, he was evaluated for
coagulation disorders, autoimmune disorders and
hematological disorders.
His serum homocysteine levels were very high
(25.6meq/L), however, other parameters for
hypercoagulable work up (Coagulation profile, Protein C
and S levels, antithrombin III levels, lupus anticoagulant),
autoimmune markers (ANA, dsDNA, RA) and drug screen
were normal. There were no other clinical or laboratory
features to suggest any auto immune disorders or
underlying malignancy.
International Study on Cerebral Vein Thrombosis (ISCVT)
reported that headache (89%), paresis (37%),
generalized (30%) or focal (20%) seizures, papilledema
(28%), and mental status disorders (22%) were the most
frequent presenting symptoms and signs associated with
the diagnosis of CVT.
Etiology:
CVT is usually multifactorial. Multiple etiologies may be
present in the same patient and evaluation must be done
for associated conditions depending on the clinical
scenario. Pregnancy and puerperal state are commonly
associated with CVT in women. Hyperhomocysteinaemia
is an independent risk factor for CVT and has been found
in around 30% of patients, whether low folate levels also
predispose to CVT is not known. Prothrombotic conditions
like congenital anomalies of coagulation pathway should
be evaluated if no other apparent predisposing
conditions are present.

C. How can we manage this patient?

He was started on anticoagulants (low molecular weight
heparin), antiepileptics and measures to reduce intra
cranial pressure (Mannitol). Patient improved
symptomatically, his headache resolved and was
discharged on oral anticoagulants with advice to monitor
PT/INR levels regularly.

Discussion
Cerebral venous thrombosis (CVT) refers to occlusion of
both superficial and deep venous system of brain including Predisposing conditions
superior sagittal sinus, transverse sinus, straight sinus and Genetic prothrombotic states
deep veins of brain. CVT is a rare cause of stroke · Protein C, S or antithrombin deficits
accounting for around 5 cases per million of population, · Factor V Leiden,
though it is three times more common in women than in men. · Prothrombin 20210 GA
Presentation of CVT can be acute to chronic. The · methylenetetrahydrofolate – reductase (MTHFR)
presenting symptoms can vary from focal syndromes like mutations
focal seizures, focal weakness to encephalopathy. Patient Acquired prothrombotic states
can present with signs of raised intra cranial tension
· Antiphospholipid antibody syndrome
(papilledema, vomiting, transient visual obscurations),
· Vasculitis
multiple cranial nerve palsies or cavernous sinus syndrome
· Lupus, Behçet's disease, Wegener's granulomatosis
(proptosis, chemosis, fifth/third/sixth nerve palsies). The

Vol. 11, Issue 4, October 2012

Other inflammatory diseases Diagnosis:
· Inflammatory bowel disease, sarcoidosis Computerized Tomography (CT) scan of the brain is the
· Malignancy initial imaging modality in clinical practice. CT Brain is
· Any cancer, including CNS tumours usually normal in CVT or may show focal hemorrhage or
· Haematological nonmalignant diseases infarct. Occasionally signs of CVT like hyperdensity of
· Polycythaemia, thrombocytopenia, severe anaemia thrombosed sinuses may be seen. The gold standard for
· Thyroid disorders diagnosis of CVT is MRI to demonstrate thrombosed vessel
· Dural arteriovenous fistulae along with MR Venography to demonstrate non
· visualization of the thrombosed vessel. Parenchymal
Precipitating Factors abnormalities like infarct of hemorrhages can be
· Infections brain, meninges, ears, sinuses, etc.
visualized by diffusion weighted images (DWI) or
· Pregnancy, puerperium
gradient recoil echo(GRE) images. The imaging diagnosis
· Neurosurgery, recent head trauma, lumbar puncture,
of CVT is not easy and inter observer variation is
jugular catheter
significant.
· Surgery
· Dehydration
Prognosis:
· Illicit drugs
· Oral contraceptives
The acute fatality rate in CVT is around 4%, usually in
· Other drugs patients with signs of raised ICP. The overall functional
· L-asparaginase, other cytotoxic drugs, tamoxifen, outcome of CVT is much better than arterial stroke with
steroids, androgens, oestrogen replacement therapy most of the patients recovering without sequlae.

Clinical Suspicion of CVT

MRI T2*-weighted imaging + MRV No evidence of CVT

CT/CTV if MRI not readily available Consider other differential diagnosis
Arterial stroke
Idiopathic intracranial hypertension
CVT (Confirmed by imaging) Meningitis
Idiopathic intracranial hypotension
Brain abscess
Initiate anticoagulation (IV heparin or SC LMWH) Brain neoplasm
If no major contraindications among other

Neurological improvement Neurological deterioration

or stable or coma despite medical treatment

Continue oral anticoagulation Severe mass effect for No or mild mass effect on
For 3-12 months or lifelong ICH on repeated imaging repeated imaging
according of the underlying etiology
a. Transient reversible factor
b. Low-risk thrombophilia
c. High-risk / inherited thrombophilia May consider decompressive May consider endovascular
Severe mass effect for ICH on repeated imaging hemicraniectomy therapy (with or without
(lifesaving procedure) mechanical disruption)

All patients should receive support for the prevention of complication and symptomatic therapy
(eg, management of seizure, intracranial hypertension)

Vol. 11, Issue 4, October 2012

Treatment:
The treatment of CVT includes management of
predisposing condition, anti thrombotics, lowering
intracranial pressure and symptomatic treatment for
seizures, headaches and visual failure. A proposed
algorithm for treatment of CVT is given below.
Anticoagulation with IV heparin (1000 U/ h, APPT
1.5–2.5x control, for no more than 7 days) or SC low
molecular weight heparin followed by warfarin with a
target INR between 2 and 3 is recommended for all
patients with CVT, regardless of the clinical presentation
and imaging features. Warfarin should be maintained for
6 months, or longer (eventually for life) in patients with
genetic or acquired prothrombotic conditions.
Pearls:
• CVT can present with various neurological deficits and
a high index of suspicion with Neuroimaging is
essential for diagnosis.
• Evaluation of predisposing conditions like
hypercoagulable states and hyperhomocystenimia
should be done.
• Treatment of the underlying condition, anticoagulants
and reducing intracranial pressure are the three
fundamental therapeutic interventions.
References
1. Saposnik G, Barinagarrementeria F, Brown RD Jr,
Bushnell CD, Cucchiara B, Cushman M, et al;
American Heart Association Stroke Council and
the Council on Epidemiology and
Prevention.Diagnosis and management of
cerebral venous thrombosis: a statement for
healthcare professionals from the American Heart
Association/American Stroke Association. Stroke.
2011 Apr;42(4):1158-92.
2. Bousser MG, Ferro JM.Cerebral venous
thrombosis: an update. Lancet Neurol. 2007
Feb;6(2):162-70.
3. Ferro JM, Canhao P. Cerebral venous and dural
sinus thrombosis. Practical Neurology, 2003, 3,
214–219
4. Stam J. Thrombosis of the cerebral veins and
sinuses. NEJM 2005; 352: 1791–98.

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Vol. 11, Issue 4, October 2012

 A Patient with Fever and Skin Lesion - A Case Report

Dr Ashok Grover and Dr Pankaj Nand Choudhary

Mrs SK 24 year old female with Procalcitonin – Normal, urine R/M –
complaint of high grade continuous fever Normal, MP antigen, dengue, typhoid &
for 6 day associated with chills and leptospira serology were negative, HIV
rigors. She developed giddiness, nausea was negative, urine and blood culture
vomiting headache followed by altered did not show any growth.
sensorium a day prior to admission.
CXR showed mild haziness at left lower
No history of seizure, burring of vision or
zone, USG abdomen showed hepato-
pain abdomen. splenomegaly, MRI brain was normal.
There was no significant past history.
CSF study showed protein 40mg%,
glucose 88mg%, cells 20 (L 90%),
On examination:
coagulam absent, India ink negative,
Pulse 116/min, BP 90/60 mmHg, pallor
Gm stain – no organism seen, PCR for
++, icterus +, Temp 990F, Chest – harsh
MTB negative, HSV I / II negative.
vesicular breath sounds, CVS - S1S2
normal, CNS-There was no focal Provisional diagnosis
neurological deficit but patient was Acute febrile illness with rash with
restless, not following verbal commands, altered sensorium
pupils b/l NS/NR, neck rigidity absent a D/D Viral encephalopathy
& planters were b/l withdrawal. Meningococcemia
Sepsis encephalopathy
Examination of skin revealed maculo-
papular rash over abdomen, back and Course during hospitalization
lower extremities. Patient was shifted to medical intensive
care unit, and put on Ceftriaxone 2gm
Investigation on admission: i/v BD, and other supportive treatment
on day 3 general condition of the
Hb 9.6 gm%
patient deteriorated, BP fell to 80mmhg
CRP 266 mg% systolic with HR of 140/min, SPo2 was
S Albumin 2.78 mg% 90% on high flow 02, examination of
chest revealed B/L basal crepts. ABG
TLC 15.08/cumm showed type I respiratory failure. CXR
S. bilirubin(T) 4.93mg% showed B/L haziness suggestive of
AlP04 570 U/L ARDS/acute pulmonary edema. Patient
was intubated and put on ventilator
Polymorphs 81% support and was put noradrenaline
SGOT 90 IU/L infusion.
Dr Ashok Grover Blood urea 74.6 mg%
Echocardiography showed hyporkinesia
Sr. Consultant Physician & Platelet count 40000/cumm of LV with EF of 20%, Pro-BNP was
Chest Specialist 2391pg/ml. CECT thorax was done
SGPT 52 IU/L
Dr Pankaj Nand Choudhary which showed B/L symmetrical ground
Consultant Physician S.creatinine 0.86 mg%
glass opacities with consolidation
Department of Medicine K+ 2.90 meq/l involving B/L lung fields likely
Pushpanjali Crosslay Hospital suggestive of ARDS.
PT/INR Normal
NCR-Delhi Patient developed high grade fever
Na + 131 meq/l (1060F) on 5th Jan 12, culture send form

Vol. 11, Issue 4, October 2012

ET secretions were positive for enterobacter cloacae
which was sensitive to tigicycline. Patient was put on broad
spectrum antibiotics (tigicycline, meropenam and
teicoplanin). Meanwhile patient developed echymotic
rashes over both lower limbs and abdomen. Scraping was
taken and Gm stain revealed no organism.
Patient continued to deteriorate, tracheostomy was done
on 7th Jan. On 12th Jan patient desaturated, went into
peripheral circulatory failure and had a cardiac arrest
and died.
Discussion:
Probable diagnosis of this case is Meningococcemia is
caused by Neisseria meningitidis, an encapsulated gram-
negative diplococcus. Acquisition of N meningitidis can
result in asymptomatic pharyngeal colonization or
invasive disease. There are at least 13 serogroups, with
the most important being serogroups A, B, C, and W-135.
Meningococcemia is defined as dissemination of
meningococci into the bloodstream and is a medical
emergency, making early recognition of the disease
essential.
Patients with acute meningococcal infection can present
clinically with one of 3 syndromes: meningitis, meningitis
with meningococcemia, or meningococcemia without
obvious meningitis.
Pathophysiology
Humans are the only known reservoir of N meningitis and
can transmit the organisms by aerosols or nasopharyngeal
secretions. Meningococcal infection is preceded by
nasopharyngeal colonization. Attachment to the
nasopharyngeal epithelial cells is aided by meningococci-
expressed pili, such as the type IV pilus encoded, which
binds to human cell surface protein CD4 6. Meningococci
then enter the bloodstream and spread to specific sites,
such as the meninges or joints, or disseminate throughout
the body. Five percent of individuals become long-term
carriers, most of whom are asymptomatic.
Meningococci have 3 important virulence factors, as
follows:
A polysaccharide capsule (which also determines the
serogroup) enables the organism to resist phagocytosis.
A lipo-oligosaccharide endotoxin (LOS) can be shed in
large amounts by a process called blebbing, causing
fever, shock, and other pathophysiology. This is
considered the principal factor that produces the high
endotoxin levels in meningococcal sepsis. Meningococcal
LOS interacts with human cells, producing
proinflammatory cytokines and chemokines, including
Vol. 11, Issue 4, October 2012
interleukin 1 (IL-1), IL-6, and tumor necrosis factor (TNF).
LOS is one of the important structures that mediate
meningococcal attachment to and invasion into epithelial
cells.
An immunoglobulin A1 protease cleaves lysosomal
membrane glycoprotein-1 (LAMP1), helping the organism
to survive intracellularly.
Individuals with immunity against meningococcal
infections have bactericidal antibodies against cell wall
antigens and capsular polysaccharide. A deficiency of
circulating antimeningococcal antibodies is associated
with disease.
Impairment of the protein C anticoagulation pathway
leads to the development of purpura fulminans in
meningococcemia.
Endotoxin, cytokines, and free radicals damage the
vascular endothelium, producing platelet deposition and
vasculitis.
Serogroups A, B, and C account for most cases worldwide.
Serogroups A and C predominate in Asia and Africa, and
serogroups B and C predominate in Europe, North
America, and South America.
Up to 95% of patients with meningococcal disease have
meningococcemia and/or meningitis. Up to 50% have
meningococcemia without meningitis. Fulminant
meningococcemia occurs in up to 20%. Nosocomial
transmission to patient care personnel and laboratory
staff is rare.
Persons with meningococcal disease may present with a
nonspecific prodrome of cough, headache, and sore
throat. This is followed by rapid onset of fever with chills,
arthralgias, and myalgias. The potential rapidity of
progression cannot be stressed enough.
In fulminant meningococcemia, collapse occurs within a
few hours, with rapid enlargement of petechiae and
purpuric lesions.
Patients with meningococcal disease appear severely ill.
Tachycardia and mild hypotension are present.
Fever is moderate. High fever is present in fulminant
meningococcemia.
Cutaneous manifestations of meningococcemia are
common and can be the presenting sign of disease.
Petechiae are the most common sign, occurring in 50-60%
of patients with meningococcemia; however, urticarial
and maculopapular lesions also may occur initially.
Petechiae are most often located on the extremities and
trunk but may progress to involve any part of the body.
Petechiae may appear in groups under areas of
pressure.
With progression of meningococcemia, pustules, bullae,
and hemorrhagic lesions with central necrosis can
develop. Stellate purpura with a central gunmetal-gray
hue is characteristic and should be considered highly
suggestive of meningococcemia.
Large maplike purpuric and necrotic areas related to the
development of DIC are characteristic of fulminant
meningococcemia.(Purpura Fulmanis)
Congestive heart failure, gallops, and pulmonary edema
may be present. Other evidence of end-organ damage
may also rapidly appear.
Patients with fulminant meningococcemia rapidly
deteriorate clinically, with hypotension and respiratory
failure.
Pericarditis can occur during the acute disease or in the
recovery period and is associated with serogroup C
disease.
Differential Diagnoses
· Dengue Fever
· Gonococcal Infections
· Influenza
· Mycoplasma Infections
· Rocky Mountain Spotted Fever
· Streptococcus Group A Infections
· Streptococcus Group B Infections
· Thrombotic Thrombocytopenic Purpura
Laboratory Studies
Definitive diagnosis of meningococcal infection requires
culture of meningococci from blood, spinal fluid, joint
fluid, or, occasionally, from skin lesions.
Cultures produce transparent, nonpigmented colonies
that are oxidase positive and nonhemolytic.
The sensitivity of blood culture is 60%-80% in
untreated patients.
Cerebrospinal fluid (CSF) culture yields a sensitivity of
up to 70% in untreated patients.
Polymorphonuclear leukocyte levels are usually
elevated, but they may be within the reference range
or low.
Vol. 11, Issue 4, October 2012
Thrombocytopenia may be present.
In meningitis, the CSF can be turbid in appearance, with
elevated pressures and proteins, and low glucose levels.
In very early infections, CSF examination results may be
normal.
CSF Gram stain yields a sensitivity of approximately
50% in patients with meningococcal meningitis. It can
have a higher yield than blood cultures.
Detection of meningococcal capsular polysaccharide in
CSF may be used for rapid diagnosis. It is sensitive for A
and C polysaccharides.
Gram-negative diplococci may be observed in punch
biopsy and needle aspiration specimens of skin lesions
or buffy coat preparations. Gram-negative diplococci
may also be recovered from joint fluid. Findings on
Gram stains of skin lesions remain positive for up to 2
days after the start of antibiotics and form a rapid
means of diagnosis, including when meningitis is not
present and when spinal fluid culture findings are
negative owing to the administration of antibiotics.
Chest radiography is useful to evaluate for pneumonia
and acute respiratory distress syndrome.
Echocardiography can be used to evaluate for
myocardial dysfunction and pericarditis.
Treatment
Antimicrobial therapy is directed toward treatment of
active infection or used prophylactically to protect those
exposed to N meningitidis through close contact.
Drugs effective in treating active meningococcal infection
include penicillin G, chloramphenicol in patients who are
allergic to penicillin, and some cephalosporins (ie,
cefotaxime, ceftriaxone, cefuroxime) used to treat
pediatric patients.
Individuals with at least 4 hours of close contact with an
index patient during the week before onset of illness are at
an increased risk of infection. Individuals at risk include
housemates, daycare contacts, cellmates, or individuals
exposed to infected nasopharyngeal secretions (eg,
through kissing, mouth-to-mouth resuscitation, intubation,
suctioning).
Rifampin and ciprofloxacin are commonly used for
chemoprophylaxis. Rifampin may eradicate carriage in up
to 80-90% of individuals, but resistant strains have
occurred. Other agents that can be used include
ceftriaxone and azithromycin. A single dose of
intramuscular ceftriaxone may be used in children or
adults. Vaccination should be adjunctive to antibiotic
chemoprophylaxis in susceptible contacts in epidemics.
 Communication for Doctors

Dr RCM Kaza
Director Professor Surgery
Maulana Azad Medical College
New Delhi
Communication is an essential skill for
any doctor. This aspect of a doctors’ work
is often not given the attention it deserves
in medical education, and unfortunately
leads to many misunderstandings in
Doctor-patient relationship. These skills
are neither rare nor difficult to acquire.
However, they need attention and
cultivation.
Broadly, communication may be defined
as the process of mutual exchange of
information and understanding by any
effective means. Special attention needs
to be paid to non-verbal communication
by way of emotional expression or body
language, whic h forms 90% of
comm unication. Therefore, it is
mandatory to attend to non verbal cues
to ensure an effective communication.
Often, the body and words speak in a
different language which serves to block
the message that is intended to be
delivered.
Counseling is yet another essential skill
for the medical practitioner. There are
many difficult decisions that the patient
may have to make about their health. It is
the duty of the doctor to help them make
those decisions. Patients trust their doctor
explicitly and implicitly. Thus, a face-to-
face interaction between the Doctor and
patient is the best environment that helps
the patient taking the final decision. In
fact, counseling demonstrates in an
admirable way, all the features of an
effective transaction such as active
listening, empathy, the art of open ended
questions and clear explanations.
Despite best efforts, communication may
fail many a time and with disastrous
consequences. In order to understand the
Dr RCM Kaza
reasons and avoid failures, it is
necessary to understand the process of
communication. There are various
aspects in this process which functions as
a unitary whole. The individual who
starts the communication may be
designated the sender. The sender
encodes thoughts and ideas and sends
them out to the receiver who has to
decode them to understand them. The
intermediaries are the language of
communication, and the medium, which
the speaker wishes to use. All these are
interlinked and any break in the chain
results in failure of communication.
There are many barriers to effective
communication. These are perception
barrier, Inflection barrier, Inference
barrier, Language barrier and so on.
Each of these barriers may have many
underlying issues that impinge on
effective communication. A detailed
understanding of these barriers is
essential for successful communication.
However, at the heart of communication
between a Doctor and patient is the art
of listening also called active listening.
Active listening is a skill by which a
Doctor not only listens to the patient but
also effectively conveys to the patient
that they are listening. This may be done
verbally or by body language. This kind
of careful listening helps the doctor
understand/decode the patient’s
problems and concerns. During such
interactions, patients convey disease
detail and also their worries, concerns
and attitudes. All these issues are
framed by the patient in their own
language, with their own nuances in an
encoded fashion. The art of active
listening requires attention and practice.
This can be demonstrated and practiced
until it becomes a habit.

December 2012

Dr Ishwar S Gilada
Secretary General Peoples Health
Organisation (India) - PHO
President, AIDS Society of India
Chairman, Unison Medicare &
Research Centre
December 2012
Current HIV Scenario and India’s Concerted Action -
Plan to Tackle the Epidemic:
In the run-up to the World AIDS Day,
several success stories from many parts
of the country helps turning it into a Day
of Celebration PHO, the country's first
NGO in the crusade against AIDS since
1985, had established in 2004 that HIV
was leveling off in Mumbai, as it had
seen a downward trend among sex
workers and flattened graphs among
general population. Any change, upward
or downward, in rates of HIV or Sexually
Transmitted Diseases happens in high-
risk population, is subsequently followed
by a similar trend in general population
with a gap of 5-7 years.
The global AIDS Epidemic has completed
30 years of its devastating presence. HIV
care in India has completed 25 years.
The AIDS virus is perplexing as it moves
slower than other infective organisms,
thus permitting years of symptom-free
infectivity. Despite ranking third in HIV
numbers, because of its affordable anti-
HIV drugs India globally prevents deaths
and ameliorates the suffering of millions
of HIV+ people.
Initially HIV was found mainly in Sex
Workers and professional blood donors
and their clients/buyers. Today, the
disease has entered the third phase of
epidemic with housewives and children
being infected with HIV. It has gone from
Urban to Rural areas, crossed from high-
risk to low risk and from sex workers to
housewives. In India, there is a massive
single male- migration to industrialized
cities/towns, and sex with multiple and
often-unknown partners is an established
behavior in males between 20-45 years
of age. There are persons traveling for
their business and having good time just
for fun, including sex indiscreetly.
HIV infection is truly a preventable
infection. Both the monetary and human
costs for prevention are far less when
compared to costs of treatment. The cost
of HIV management in India is far less
than in western countries.
Ishwar S Gilada
Death is generally not due to HIV
infection itself, but the opportunistic
infections (OIs) that occur when the
immune system can no longer protect the
body against agents normally found in
the environment or the secondary
cancers. The appearance of any one of
more than 25 different OIs, along with a
CD4 count less than 200 cells per c/mm
of blood provides the clinical diagnosis
of AIDS in HIV-infected individuals. The
most common OI seen in HIV is TB in India
and Pneumocystis carinii pneumonia
(PCP) in the western countries. Bacterial
pneumonia and PCP, caused by the
fungus Pneumocystis jiroveci are also
commonly associated. In the late phase
Miliary TB, Extra-pulmonary TB and
bacterial infection by Mycobacterium
avium can cause fever, weight loss,
anemia and constipation alternating
with diarrhea. Bacterial infections of the
GIT commonly cause diarrhea, weight
loss, anorexia and fever. Most common
diarrhea is caused by Cryptosporidia,
Microspora and Isospora Belli
organisms, giving rise frequent watery
stools. During advanced stage, diseases
caused by protozoal parasites,
especially toxoplasmosis and fungus
especially cryptococcosis of the brain
are common. In addition people with
AIDS often develop other fungal
infections. Thrush, an infection of the
mouth by the fungus Candida albicans, is
most common from the early phase.
The disease forecast of early 1990s has
c hanged to become a c hronic
manageable disorder now. People
infected with HIV can survive up to 30
years now – 10-15 years without ART
and another 15 years on ART. However,
this is possible if the patient is under
medical care and follows healthy
lifestyle protocol, regular treatment and
meticulous follow-ups. Alcohol,
recreational drugs, smoking and
tobacco hastens disease progression
and hampers recovering process.
Treatment for only richer countries and the rich in poorer
countries has become affordable to most countries. India is
at crossroads vis-à-vis HIV that it makes imperative to look
back in the recent past, take stock of what has been
achieved and what has been amiss in order to decide
future plan for a better tomorrow. The Saving grace for
larger Indian population from HIV is the Indian culture, the
responsiveness of its youth, efforts of voluntary NGOs and
medical caregivers and yeomen contribution of our
pharma lobby.
Treasure India’s Asset: India’s clinically oriented,
conservative, comprehensive and holistic care has earned
accolades. Its wait-n-watch approach in starting anti-
retroviral treatment (ART) is indeed blessing in disguise for
HIV patients (as against ‘Hit-Early, Hit-Hard’ approach of
the West). It improves quality of life, increases survival,
reduces cost and spares them of impending drug-
resistance and adverse effects for years. Indian culture of
joint families and lasting marriages with integrity in women
folks have been an asset in providing psycho-social
support and reduced transmission. The age at the first sex
is higher in India than the West or Africa.
“One Tablet a Day: Keeps HIV at Bay!” treatment
invented in India made ART cheaper, safer and easier. The
yearly cost of three-in-one cheapest first-line combo has
come down from US$ 11452/- per patient to $69.
What is amiss?: India records 18,000 children getting
HIV from 65,000 HIV+ mothers annually, where as there
are strategies to prevent each of them. HIV+ women
received only single-dose Nevirapine in an outdated
strategy meant for Africa. Sadly, less than 15% of the
pregnant women received Prevention of Parent to
Children Transmission (PPTCT); only 60% of sex workers
are reached with HIV prevention program and 40% of
them identify correct ways of prevention methods. Only
30% of the infections are recorded at NACO, due to
inherent flaws in the reporting system. Half of the infected
people do not know their HIV status. Our efforts to make
the risk-takers understand their vulnerability have been
inadequate nationally. Initially, most of the national
energy and funds were wastefully spent on 'surveillance'
without 'interventions'; while only third of adults with
advanced HIV infection are receiving ART (up from 6% in
2005); while 20% patients at NACO’s free roll out are
dead, 12.5% have lost to follow-up or stopped ART in 2
years. Thanks to the Supreme Court order of 16th
December 2010, there is universal access to even Second-
line ART that includes patients treated by private
practitioners with initial regimen and with its previous
order in 1998, India’s total blood supply is HIV screened
and is safe.
December 2012
What India needs to learn? We must critically evaluate
the state-run and NGO programs, replicate best practices
and shun the unsuccessful ones. We should provide three
tiered (not free for all) ART with quality care and should
move from 'Donor-dependence' to 'Self-reliance'. We
should focus to reduce vulnerability of women and children
and make PPTCT a national emergency with 100%
coverage. There should be a strong focus on Youth and de-
addiction as more than 50% new infections are among
those below 30.
We are facing an extremely challenging situation with
Multi-drug resistant and extremely drug resistant
(MDR/XDR) Tuberculosis and HIV, Immune Reconstitution
Inflammatory Syndrome (IRIS) – a serious disease situation
caused by regaining the lost immunity following successful
ART, marriages/alliances among HIV +ve people, jobs for
recovered people and medical Insurance for them. What is
not yet discovered is effective Vaccine for HIV prevention
among risk takers and vaginal Microbicide to prevent its
transmission among women.
There is no other disease that has triggered such a fast and
quality research in short span of time. We know enough on
pathogenesis and epidemiology front. Knowledge on
AIDS is fast evolving and that necessitates timely update
of doctors providing HIV care. United Nations Secretary-
General Ban Ki-moon suggested strategy of the "three
zeros" - zero new HIV infections, zero discrimination and
zero AIDS-related deaths. Let us pledge to work together
to realize this vision for all of the world's people. India's
strategy of working on vulnerable groups at highest risk of
contracting HIV is now paying off dividends and is
projected to avert 3 million infections. India’s success
deserves praise, but there is no room for complacency.
How HIV is transmitted?
HIV is spread through the exchange of bodily fluids,
primarily semen, vaginal secretions, blood, and blood
products. It cannot be transmitted through casual contact.
There are four main modes of transmission: Sexual,
Parenteral, Perinatal and Accidental. The primary mode
of infection in India is through sexual transmission, mainly
heterosexual. The basics of each mode of transmission are
outlined here:
What is the Risk?
Occupational Needle-prick
Per- cutaneous 0.3%
Mucous membrane 0.09%
Sexual transmission (single contact) 0.018% to 3%
Mother to child (in natural course) 25%
Infected blood/ blood products 95%
 Rational Treatment of Osteoarthritis

UK Sadhoo
Consultant Orthopedic Surgeon
Pushpanjali Crosslay Hospital
NCR-Delhi
Osteoarthritis is the commonest cause of
joint pains. Its precise cause is unknown.
As longevity increases, more and more
Indians are succumbing to it. In our
country, knees are most involved though
any joint is susceptible. Besides age,
other factors such as lack of exercise,
indifferent diet and sedentary lifestyle
are all contributory factors.
Trauma, infection, inflammatory arthritis
also culminate in arthritis.
Treatment has two aspects: Surgical and
non-surgical.
Non surgical treatment includes,
a n a l ge s i c s / a n t i - i n f l a m m a t o r i e s,
Physiotherapy, exercises and weight
reduction. These can yield substantial
results. Efficacy of visco-supplements
Dr UK Sadhoo
such as Hyaluronic acid intraarticularly,
Glucosamine/Chondroitin and
acupuncture remains debatable.
Surgical options are:
1) Arthroscopy with limited benefits,
2) Osteotomy in relatively early stages
in which redistribution of stresses is
the aim and, if done for correct
indications, can yield good results
for indefinite periods and finally,
3) Joint replacement. The last option is
major surgery, costly, entails lot of
physiotherapy later to achieve full
benefits. Many patients who would
otherwise be crippled and bed-
ridden are benefiting from
Replacement surgery.

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December 2012
 Fever in the ICU
Introduction
Fever is a common problem in the ICU. It
could be due to infectious and non-
infectious causes. Our objective is to
review a rational approach to the
management of fever in ICU patients.
Definition
Fever is a co-coordinated neuro
endocrine, autonomic and behavioral
response that is adaptive, and an
essential part of the acute-phase
response to immune stimulus or tissue
injury. It is co-coordinated by the
hypothalamus with neural input from
peripheral thermoreceptors and humoral
cues from inflammation or infection.
Benefits of fever1, 2
It enhances parameters of immune
function, improves antibody production,
activates T-cells, produces cytokines and
enhances neutrophil and macrophage
function. A positive correlation has been
seen between maximum temperature on
the day of bacteremia and survival.
Temperature > 38 °C improved survival
in patients with SBP.
The downside of fever
It increases cardiac output, oxygen
consumption, carbon dioxide production
and basal metabolic rate leading to
poorer neurological outcomes in patients
with stroke and traumatic brain injury
who manifest with fever. Fever is poorly
tolerated in patients with reduced
cardio-respiratory reserve. Maternal
Dr Amit Gupta fever has been a cause of fetal
Consultant and Head, malformations as well as spontaneous
Critical Care abortions3.
Pushpanjali Crosslay Hospital
NCR-Delhi Measurement of temperature4
It includes-
l Pe r i p h e r a l t e m p e r a t u r e
measurement- It is measured in the
outer 1.6 mm of skin or mucus
December 2012
Amit Gupta
m e m b ra n e s b u t c o n s i d e r e d
unreliable as it is influenced by
environmental temperatures, mouth
breathing etc. Examples – oral
t e m p e ra t u r e, a x i l l a r y, s k i n
temperature
l Core temperature measurement - It
is not influenced by external factors
and more accurately reflects
temperature in the internal organs.
Examples – pulmonary, rectal,
esophageal, urinary, tympanic
membrane.
“Fever” in the ICU patients
Normal temperature is 98.2O F (36.8O C)
with diurnal variations of temperature
with evening rise up to 100O F (37.8O C).
Society of Critical Care Medicine
(SCCM) and Infectious diseases society
of America recommend investigations in
the ICU if temperature is above 101O F
(38.3O C).
Approach to fever in the ICU5
l What are the causes of fever in ICU?
l How do I act when I see a
temperature spike?
l What investigations do I send?
l How do I treat the fever?
The obvious focus
l Community acquired pneumonia
l Acute CNS infection
l Urinary tract infection
l Abdominal focus of infection
l Wound infection / Pus collections
l Trauma with infection
Why do these patients come to the ICU
l Ventilatory support – respiratory
failure, pneumonia
l Hemodynamic support – shock
l Renal replacement therapy – renal
failure, severe acidosis
l Monitoring, Neurological
dysfunction, Hematologic
Acute undifferentiated fever
l Fever with thrombocytopenia
l Fever with hepato-renal dysfunction
l Fever with pulmonary renal syndrome
l Fever with altered sensorium
Fever with thrombocytopenia
l Malaria (notably falciparum)
l Dengue
l Leptospirosis
l Rickettsial infections
l Viral fevers
Fever with hepato-renal dysfunction
l Malaria (falciparum)
l Leptospirosis
l Scrub typhus
l Fulminant hepatic failure
Fever with pulmonary-renal dysfunction6
l Malaria (falciparum)
l Leptospirosis
l Scrub typhus
l Hantavirus infection
l Severe legionella / pneumococcal pneumonia
Fever with altered sensorium
l Malaria – cerebral malaria
l Encephalitis
l Meningitis
l Typhoid fever
l Septic encephalopathy
l Brain abscess
Infectious causes of fever whilst in ICU
l Ventilator associated pneumonia7
l Catheter related blood stream infections
l Urosepsis
l Intra-abdominal infections
l Sinus infections
l Diarrhoea
l Fungal infections including candidemia
l Surgical wound infections
l Acalculous cholecystitis
l Endocarditis
l Meningitis
How do I act when I see a temperature spike?
l Should I be worried?
YES
l In an immunocompromised patient
l Hemodynamic instability
December 2012
Non-infectious causes of fever in ICU
Brain Cerebral infarction/hemorrhage,
sub arachnoid hemorrhage
Heart Acute myocardial infarction, pericarditis
Pulmonary Aspiration, atelectasis, pulmonary
embolism, ARDS
Abdomen Ischemic bowel, gastrointestinal bleeding.
pancreatitis, hepatitis. cirrhosis, adrenal
insufficiency
Vascular Deep vein thrombosis, thrombophlebitis
Cutaneous Decubitus ulcers
Miscellaneous Drug fever, reaction to radiological
contrast, fat embolism, neoplasms, blood
transfusions, transplant rejection. gout.
l Decreasing urine output
l Increasing lactate levels
l Worsening conscious state
l Falling platelet counts
l Worsening coagulopathy
NO
l Small spike
l No hemodynamic instability
l Carefully examine clinically for an obvious focus of
infection
Investigations
l Blood – counts with peripheral smear, procalcitonin
l Imaging – CXR, Scans as indicated (abdomen, sinus, CT
brain)
l Cultures as appropriate – ETA, BAL8, Urine, Blood
cultures (peripheral and through lines), cultures from
pus, wound etc, Stool for clostridium
l Assess if lines are “old” and if there is any evidence of
line sepsis - re-site line if indicated
l Change urinary catheter
l May need NG change – if sinus infection suspected
l Do not forget about
- Acute Lung injury/ARDS, Aspiration
- Deep venous thrombosis, thrombophlebitis
- Drug fever
- Decubitus ulceration
Treatment
l Antipyretics in patients with neurological disorders or
poor cardio-respiratory reserve.
l Administer or change antibiotics in an unstable patient
– choose to treat with broad spectrum antibiotics and
deescalate depending on cultures & clinical response.