Chronic kidney disease

Chronic kidney disease (CKD), also known as chronic renal disease, is a progressive loss of renal function over a period of months or years. The symptoms of
worsening kidney function are unspecific, and might include feeling generally unwell and experiencing a reduced appetite. Often, chronic kidney disease is diagnosed
as a result of screening of people known to be at risk of kidney problems, such as those with high blood pressure or diabetes and those with a blood relative with chronic
kidney disease. Chronic kidney disease may also be identified when it leads to one of its recognized complications, such as cardiovascular disease, anemia or
pericarditis.

Chronic kidney disease is identified by a blood test for creatinine. Higher levels of creatinine indicate a falling glomerular filtration rate (rate at which the kidneys filter
blood) and as a result a decreased capability of the kidneys to excrete waste products. Creatinine levels may be normal in the early stages of CKD, and the condition is
discovered if urinalysis (testing of a urine sample) shows that the kidney is allowing the loss of protein or red blood cells into the urine. To fully investigate the
underlying cause of kidney damage, various forms of medical imaging, blood tests and often renal biopsy (removing a small sample of kidney tissue) are employed to
find out if there is a reversible cause for the kidney malfunction.Recent professional guidelines classify the severity of chronic kidney disease in five stages, with stage
1 being the mildest and usually causing few symptoms and stage 5 being a severe illness with poor life expectancy if untreated. Stage 5 CKD is also called established
chronic kidney disease and is synonymous with the now outdated terms end-stage renal disease (ESRD), chronic kidney failure (CKF) or chronic renal failure
(CRF).

There is no specific treatment unequivocally shown to slow the worsening of chronic kidney disease. If there is an underlying cause to CKD, such as vasculitis, this
may be treated directly with treatments aimed to slow the damage. In more advanced stages, treatments may be required for anemia and bone disease. Severe CKD
requires one of the forms of renal replacement therapy; this may be a form of dialysis, but ideally constitutes a kidney transplant.

Signs and symptoms

Initially it is without specific symptoms and can only be detected as an increase in serum creatinine or protein in the urine. As the kidney function decreases:

• blood pressure is increased due to fluid overload and production of vasoactive hormones, increasing one's risk of developing hypertension and/or suffering
from congestive heart failure
• Urea accumulates, leading to azotemia and ultimately uremia (symptoms ranging from lethargy to pericarditis and encephalopathy). Urea is excreted by
sweating and crystallizes on skin ("uremic frost").
• Potassium accumulates in the blood (known as hyperkalemia with a range of symptoms including malaise and potentially fatal cardiac arrhythmias)
• Erythropoietin synthesis is decreased (potentially leading to anemia, which causes fatigue)
• Fluid volume overload - symptoms may range from mild edema to life-threatening pulmonary edema
• Hyperphosphatemia - due to reduced phosphate excretion, associated with hypocalcemia (due to vitamin D3 deficiency). The major sign of hypocalcemia
being tetany.
o Later this progresses to tertiary hyperparathyroidism, with hypercalcaemia, renal osteodystrophy and vascular calcification that further impairs
cardiac function.
• Metabolic acidosis, due to accumulation of sulfates, phosphates, uric acid etc. This may cause altered enzyme activity by excess acid acting on enzymes and
also increased excitability of cardiac and neuronal membranes by the promotion of hyperkalemia due to excess acid (acidemia)

People with chronic kidney disease suffer from accelerated atherosclerosis and are more likely to develop cardiovascular disease than the general population. Patients
afflicted with chronic kidney disease and cardiovascular disease tend to have significantly worse prognoses than those suffering only from the latter.

Diagnosis

In many CKD patients, previous renal disease or other underlying diseases are already known. A small number presents with CKD of unknown cause. In these patients,
a cause is occasionally identified retrospectively.[citation needed]

It is important to differentiate CKD from acute renal failure (ARF) because ARF can be reversible. Abdominal ultrasound is commonly performed, in which the size of
the kidneys are measured. Kidneys with CKD are usually smaller (< 9 cm) than normal kidneys with notable exceptions such as in diabetic nephropathy and polycystic
kidney disease. Another diagnostic clue that helps differentiate CKD and ARF is a gradual rise in serum creatinine (over several months or years) as opposed to a
sudden increase in the serum creatinine (several days to weeks). If these levels are unavailable (because the patient has been well and has had no blood tests) it is
occasionally necessary to treat a patient briefly as having ARF until it has been established that the renal impairment is irreversible.

Additional tests may include nuclear medicine MAG3 scan to confirm blood flows and establish the differential function between the two kidneys. DMSA scans are
also used in renal imaging; with both MAG3 and DMSA being used chelated with the radioactive element Technetium-99.

In chronic renal failure treated with standard dialysis, numerous uremic toxins accumulate. These toxins show various cytotoxic activities in the serum, have different
molecular weights and some of them are bound to other proteins, primarily to albumin. Such toxic protein bound substances are receiving the attention of scientists who
are interested in improving the standard chronic dialysis procedures used today
Stages

A Glomerular filtration rate (GFR) <60 mL/min/1.73 m2 for 3 months are classified as having chronic kidney disease, irrespective of the presence or absence of kidney
damage. The rationale for including these individuals is that reduction in kidney function to this level or lower represents loss of half or more of the adult level of
normal kidney function, which may be associated with a number of complications.

All individuals with kidney damage are classified as having chronic kidney disease, irrespective of the level of GFR. The rationale for including individuals with GFR
60 mL/min/1.73 m2 is that GFR may be sustained at normal or increased levels despite substantial kidney damage and that patients with kidney damage are at increased
risk of the two major outcomes of chronic kidney disease: loss of kidney function and development of cardiovascular disease.

The loss of protein in the urine is regarded as an independent marker for worsening of renal function and cardiovascular disease. Hence, British guidelines append the
letter "P" to the stage of chronic kidney disease if there is significant protein loss.

Stage 1 CKD

Slightly diminished function; Kidney damage with normal or relatively high GFR (>90 mL/min/1.73 m 2). Kidney damage is defined as pathologic abnormalities or
markers of damage, including abnormalities in blood or urine test or imaging studies.

Stage 2 CKD

Mild reduction in GFR (60-89 mL/min/1.73 m2) with kidney damage. Kidney damage is defined as pathologic abnormalities or markers of damage, including
abnormalities in blood or urine test or imaging studies.

Stage 3 CKD

Moderate reduction in GFR (30-59 mL/min/1.73 m 2). British guidelines distinguish between stage 3A (GFR 45-59) and stage 3B (GFR 30-44) for purposes of screening
and referral.

Stage 4 CKD

Severe reduction in GFR (15-29 mL/min/1.73 m2)[1] Preparation for renal replacement therapy

Stage 5 CKD

Established kidney failure (GFR <15 mL/min/1.73 m2, or permanent renal replacement therapy (RRT)[1]

Causes

The most common causes of CKD are diabetic nephropathy, hypertension, and glomerulonephritis. Together, these cause approximately 75% of all adult cases. Certain
geographic areas have a high incidence of HIV nephropathy.

Historically, kidney disease has been classified according to the part of the renal anatomy that is involved, as

• Vascular, includes large vessel disease such as bilateral renal artery stenosis and small vessel disease such as ischemic nephropathy, hemolytic-uremic
syndrome and vasculitis
• Glomerular, comprising a diverse group and subclassified into
o Primary Glomerular disease such as focal segmental glomerulosclerosis and IgA nephritis
o Secondary Glomerular disease such as diabetic nephropathy and lupus nephritis
• Tubulointerstitial including polycystic kidney disease, drug and toxin-induced chronic tubulointerstitial nephritis and reflux nephropathy
• Obstructive such as with bilateral kidney stones and diseases of the prostate

Treatment

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The goal of therapy is to slow down or halt the otherwise relentless progression of CKD to stage 5. Control of blood pressure and treatment of the original disease,
whenever feasible, are the broad principles of management. Generally, angiotensin converting enzyme inhibitors (ACEIs) or angiotensin II receptor antagonists (ARBs)
are used, as they have been found to slow the progression of CKD to stage 5. Although the use of ACE inhibitors and ARBs represents the current standard of care for
patients with CKD, patients progressively lose kidney function while on these medications, as seen in the IDNT and RENAAL studies, which reported a decrease over
time in estimated glomerular filtration rate (an accurate measure of CKD progression, as detailed in the K/DOQI guidelines) in patients treated by these conventional
methods.

Currently, several compounds are in development for CKD. These include, but are not limited to, bardoxolone methyl, olmesartan medoxomil, sulodexide, and
avosentan

Replacement of erythropoietin and vitamin D3, two hormones processed by the kidney, is usually necessary in patients with CKD, as is calcium. Phosphate binders are
used to control the serum phosphate levels, which are usually elevated in chronic kidney disease.

When one reaches stage 5 CKD, renal replacement therapy is required, in the form of either dialysis or a transplant.

In some cases, dietary modifications have been proven to slow and even reverse further progression. Generally this includes limiting a persons intake of protein

Prognosis

The prognosis of patients with chronic kidney disease is guarded as epidemiological data has shown that all cause mortality (the overall death rate) increases as kidney
function decreases. The leading cause of death in patients with chronic kidney disease is cardiovascular disease, regardless of whether there is progression to stage 5.

While renal replacement therapies can maintain patients indefinitely and prolong life, the quality of life is severely affected.[13][14] Renal transplantation increases the
survival of patients with stage 5 CKD significantly when compared to other therapeutic options; however, it is associated with an increased short-term mortality (due to
complications of the surgery). Transplantation aside, high intensity home hemodialysis appears to be associated with improved survival and a greater quality of life,
when compared to the conventional three times a week hemodialysis and peritoneal dialysis.

Why separate acute from chronic renal failure?

- Management is different
- Manifestations may be similar
- Prognosis is different: Chronic Renal Failure – irreversible; Acute Renal Failure – reversible

Functions of the Kidney Measured

using:
Excretory function BUN, creatinine

Maintenance of Acid – Base pH, HCO3,

pCO2
Balance
Maintenance of Fluid and Osmolality,
water, Na, K, Cl
Electrolyte Balance
Maintenance of Ca-Phosphate Ca, Phosphates
(Mg)
Balance
(Mineral balance)
Vitamin D production Calcium

Erythropoeitin Production Hgb, hct for

confirmation

Chronic Renal Failure (CRF)

-Pathophysiologic process which is a result of varied conditions that leads to irreversible destruction of
nephrons, ultimately leading to End Stage Kidney Disease (ESRD).
-Sum of all processes that happen cause by various diseases such as DM, hpn, GN, lupus, secondary causes due to multiple myeloma, etc.
- Slow deterioration of kidney function
- Loss of nephrons  other nephrons try to compensate
during CRF phase, you don’t see manifestations of ESRD
- Normal GFR men:100ml/min; women:85ml/min
- Just keep in mind that the key word in CRF is COMPENSATION
- DO NOT MAKE THE MISTAKE OF DIALYSING A PATIENT WITH CRF!
Spectrum of CRF:

Normal kidney CRF (>3mos) ESRD

Pathophysiology
-Long term reduction of renal mass / function which initially leads to compensatory hypertrophy and function. Eventually
this leads to sclerosis of the remaining nephron, resulting to ESRD.

Stages of Chronic Renal Disease

Stage Description GFR, mL/min

per 1.73 m2
1 At increased risk of 90 (with CRD
kidney damage with risk factors)
normal or increased 90
GFR
2 Kidney damage with 60-89
mildly decreased GFR
3 Moderately decreased 30-59
GFR
4 Severely decreased 15-29
GFR
5 Renal Failure (ESRD) < 15

GFR
• CRF: 16-89 mL/min
• ESRD: <15 mL/min

Difference between CRF & ESRD in terms of Pathophysiology

CRF – there is hyperfiltration, some amount of compensation

ESRD – no more compensation; all other organ systems will end up with some kind of dysfunction

Chronic End-Stage
Kidney
Renal Failure Renal Disease
Function
(CRF) (ESRD)
Excretory No signs / Nausea /
Function symptoms vomiting
↑ BUN ↑↑ BUN
↑ Creatinine, ↑↑ Creatinine,
↑ Cystatin C ↑↑ Cystatin C
Maintenance No ↑ RR –
of Acid- Manifestations Kussmaul
 Base Normal acid- breathing
Balance base balance Metabolic
Acidosis
Maintenance ↑ RR
of Fluid & ↑ BP Arrythmia
Electrolyte NVE NVE
Balance Crackles Crackles
Edema Edema
Na – Normal Na – Normal
K – Normal or K–↑
↑
Maintenance No Osteitis fibrosa
of Calcium- manifestations cystica
Phosphate ↑ Phosphate ↑↑ Phosphate
Balance ↓ Ca ↓↓ Ca
Vitamin D No Osteomalacia
Production manifestations ↓ Calcitriol
↓ Calcitriol
(see diagram
below)
Erythropoiet Weakness Weakness
in Dizziness Dizziness
Production Pallor Pallor
Easy Easy
Fatigability Fatigability
↓ Hemoglobin ↓↓ Hemoglobin
Excretory function:
• ≤1.5mg creatinine
• 10-20 BUN depending on level of hydration
• Cystatin- only used in lab research for now
Maintenance of Acid-Base Balance:
• Still with compensation
Maintenance of Fluid & Electrolyte Balance:
• For fluids, think also of sodium going along with it
• Creatinine clearance >60, accumulation of Na
• Increased BP: CM, lupus, GN
• No signs/symptoms, normal BP: may also have renal failure, creatinine worsening
• Buko juice: causes hyperkalemia; so AVOID DRINKING BUKO JUICE WHEN YOU HAVE KIDNEY PROBLEMS UNLESS YOU HAVE LOW POTASSIUM
• Buko juice, bananas  good fore people with diarrhea
• Nephrologists should therefore identify patients are Na or K wasters. If this is the case then don’t let them avoid Na of K.
Maintenance of Calcium-Phosphate Balance
• >25% creatinine clearance is still normal
Vitamin D Production
• Calcitriol- only in lab research for now
• (Please refer to table at last page) Why is there an increase in phosphates in ESRD?  because the poorly functioning kidney can’t eliminate them all. The
phosphate binds with calcium  leading to a decrease in ionized calcium  leading to secondary hypoparathyroidism
Erythropoietin Production
• In DM, anemia occurs early

Management of Chronic Renal Failure

A. Comprehensive strategy for renoprotection in patients with chronic renal disease
Intervention Therapeutic Goal
Specific renoprotective
therapy Proteinuria <0.5 g/day
ACE inhibitor or GFR decline <2
ARB treatment ml/min/year
Specific renoprotective
therapy Proteinuria <0.5 g/day
ACE inhibitor or GFR decline <2
ARB treatment ml/min/year
Adjunctive cardiorenal
protective therapy
Additional <130/80 mm Hg
antihypertensive
therapy
Dietary protein
restriction 0.6-0.8 g/kg/day
Dietary salt 3-5 g/day
restriction
Tight glycemic AIC < 6.05 %
control in diabetes Normal values
Reduce elevated
calcium-phosporous

Lipid lowering therapy LDC-C <100mg/dl

Anti-platelet therapy Thrombosis
prophylaxis
Consider correction of Hb > 12g/dl
anemia
Smoking cessation Abstinence
Weight control Ideal body weight
• Level of proteinuria determines the level of dietary protein restriction in patients
• Reduce elevated electolyte Ca and P if <25%, it merits checking
• The lecturer considers correction of anemia if Hb 11-12g/dl
• Lipid lowering therapy (Statins)

B. Avoid insults to the kidney

•Volume depletion- diarrhea
•Nephrotoxins- aminoglycosides, radiocontrast material
•NSAID- COX2 inhibitors, mefenamic acid, naproxene, indomethacin
C. Preparation for ESRD management
• Psychological
• Renal Replacement Therapy, options
o Dialysis – Vascular Access
 o Transplant – Recipient Donor Work-Up
* with a creatinine clearance of 20 or 25, you can start discussing dialysis with the patient

End Stage Renal

Disease
Please see table on first page
Excretory function:
 Nausea and vomiting- SSX of accumulation of BUN, creatinine
Maintenance of Acid-Base Balance:
• metabolic acidosis
Maintenance of Fluid & Electrolyte Balance:
• body can’t eliminate waste products because it can’t compensate; arrhythmia due to increased K
Maintenance of Calcium-Phosphate Balance
• Phosphate retained, binds to Ca, absence of Vit D3 decreased gut absorption of Ca
Vitamin D Production
Erythropoietin Production

•Anemia insidious in onset  so you may have SSX in ESRD

Pathophysiology: fibrosis – no more compensation in whatever aspect of excretion

Management of ESRD

A. Supportive
1. Nutrition
2. Psychological
3. Control BP
4. Maintain Hb at 110-120 g/dl with erythropoietin oral iron is not absorbed very\well by uremic patient; it’s better to give it to
them IV
5. Fluid and electrolyte balance
6. Acid-base homesotasis
7. Maintain Ca and Phosphate balance – give Calcium carbonate or Calcium acetate with meals. You eat meat, and meat has
phosphate. Para habang nakakapagbigay ka ng calcium, nakakapag prevent ka na rin ng absorption ng phosphate. You “shoot two birds with one stone”
B. Renal Replacement Therapy
1. Dialysis
2. Hemodialysis
3. Peritoneal Dialysis
4. Transplant
5.
- Consider dialysis if creatinine clearance is about 20ml/min
- Uremic symptoms present with nausea and vomiting. If the disease is not ESRD, consider other etiologies for the said symptoms
- Excess fluid in the body – volume overload – diuretics won’t help coz kidneys are already sclerosed

Renal Replacement Therapy in CRF

- indicated when metabolic abnormalities can no longer be controlled with conservative management or when
signs and symptoms of uremia developed
- No absolute value in terms of CR by which you will start your RRT

Indications for Dialysis

- volume overload
- intractable metabolic acidosis
- hyperkalemia
- uremic state (encephalopathy, pericarditis)
- azotemia without uremic manifestations

CASE

A 24-year old male diagnosed with chronic glomerulonephritis was admitted for nausea and vomiting.
Maintenance of ACE inhibitors with HCTZ (Hydrochlorothiazide) was given.

His last follow-up a week ago showed a Cr 1.8 mg%. Three days PTA he had copious diarrhea and was unable
to take anything including medicines. He noted decreased urine output. He felt weak and later developed nausea
and vomiting.

PE: BP = 90/60 PR = 110/min RR = 25/min

Sunken eyeballs, dry skin and mucous membranes
BUN 80mg/dL; Cr 10mg/dL; K 6meq/L; Na 132 meq/L
ABG: pH 7.2; HCO3 11meq/L; CO2 20meq/L
Hgb: 15gm/dl (N14-17)
Hematocrit: 45 (hemoconcentrated)
Urinalysis: Sp gr = 1.010, (4+) protein, (–) sugar
4-5 RBCs/hpf, 10-15 WBCs/hpf

What is your diagnosis?

a. Acute renal failure
b. Chronic renal failure
c. End stage renal failure
d. Acute on chronic renal failure

Answer: Acute on Chronic Renal Failure

What finding tells us that the patient has renal failure?

a. K
b. pH
c. creatinine
d. urinalysis –just a reflection that something’s wrong, but not specific for renal failure

Answer: Creatinine
What is the cause of the ABG finding?
e. Chronic GN
f. Diarrhea
g. Vomiting
h. Acute renal failure

Answer: Diarrhea and ARF (acidosis)

How should you manage this patient?
a. kidney transplant
b. dialysis
c. supportive management
d. observe

Answer: Supportive Management

Management:
 Hydrate patient
 For increased K, give sodium bicarbonate- shoot two birds with one stone  not only do you decrease K you also replace the lost HCO3
 Treat the cause of diarrhea
 Nutrition: don’t focus on it yet. Just follow treatment for diarrhea
 Follow up BUN, creatinine. If it improves, don’t do anything. Take note that there’s a 3-4 day period before creatinine drops.

Hypovolemia: low BP, sunken eyeballs, dry skin, mucous membrane

Increased RR implies metabolic acidosis
Hemoconcentration due to diarrhea

If the creatinine changed from 1.8 to 9mg, but the patient has nausea and vomiting, Bp=130/80, no diarrhea,
eyeballs not sunken, (+)edema, what is the management?

Decreased Renal Function Answer: Dialysis

Hyperphosphatemia
Decreased 1.25
(OH)2D3 AI3+ Intoxication Accumulation of
ß2 microglobulin
If anemic (Hb 10g/dl), what is the mgt?

Decreased
Decreased ionized
Ca2+ Answer: Give erythropoietin. If <10 g/dl,
expression
of calcium-
Hyperparathyroidism
transfusion
sensing
receptor

Hyperplasia From block B:

of the
parathyroid  Hyperkalemia – don’t give diuretics because
glands patient is dehydrated; give sodium bicarbonate ->
push K inside the
Osteitis fribrosa cystica Osteomalacia Adynamic bone Dialysis-related
(high-turnover bone disease) disease amyloidosis

Metabolic acidosis Excess Ca and vit D, PD, diabetes