CHRONIC KIDNEY DISEASE

UNDERSTANDING
PROGRESSION AND
CLINICAL CONSEQUENCES.
 PRE TEST

1. Is serum creatinine a good marker of renal function in all people

and at all ages?

2. What is the most common cause of death in those with chronic

renal failure?

3. Why is oral calcium therapy in those with chronic renal failure

both good and bad?

4. What is the target haemoglobin level when using erythropoietin?

5. What is the target BP in those with chronic renal failure?

 WHAT IS CHRONIC KIDNEY
DISEASE?
Damage to the renal parenchyma that
persists for more than 3 months.

Some types of CKD are visible on

imaging: hydronephrosis, renal calculi,
renal cysts.
CKD due to glomerular damage is
recognised by persistent proteinuria.
 WHAT ABOUT A FUNCTIONAL
DEFINITION?
Chronic kidney disease can also be
defined as a GFR less than 60ml per
minute for 3 months or more.

The difference between CKD and renal

failure is that renal failure is a GFR below
15ml per minute.
THE GLOMERULAR FILTRATION RATE IS
A PARAMETER THAT TELLS US ABOUT
THE FUNCTION OF THE KIDNEY.

The GFR to the kidney is what the Ejection

Fraction is to the heart.
 HOW DOES THE GFR HELP TO
CLASSIFY C.K.D.?
Stage 1 GFR more than 90ml per min.
Stage 2 GFR between 60 and 90
Stage 3 GFR between 30 and 60
Stage 4 GFR between 15 and 30
Stage 5 GFR below 15ml per minute.

Stage 5 CKD is renal failure

 BLOOD UREA & SERUM
CREATININE
Is this statement always true?
A normal blood urea or serum creatinine
means normal renal function.

Blood urea and serum creatinine levels

reflect the balance between production
and excretion.
 SERUM CREATININE
Increased production + normal excretion
(in African Americans)
Decreased production + normal excretion
(in elderly people)
Decreased production + decreased
excretion (elderly with early renal disease)
Normal production + Decreased excretion
(blood level reflects renal function)
 Estimated GFR
THE COCKROFT-GAULT formula for men

(140-age) times (weight in kg)

(72) times (serum creatinine) (mg/dL)

For women: multiply above by 0.85
Remember:
1. This is actually the creatinine clearance
2. Creatinine is both filtered by glomeruli and secreted by tubules
3. Normal e-GFR for men: 120ml/min, for women: 100ml/min
 ESTIMATED GFR
If the creatinine is estimated in micromoles per litre, then the Cockroft
and Gault equation for men will be:

(140 Age) multiplied by weight in kg ( multiplied by 1.23)

Serum creatinine in micromoles/L

Courtesy: MEDSCAPE
 CLINICAL CONSEQUENCES OF
CKD
More people with CKD and reduced GFR
in grades 2 to 4 actually die of CV
disease than progress to ESRD. (NEJM 2004)

Increased BP
Increased cholesterol
Increased CRP
Increased homocysteine
WE MAY NOT BE ABLE TO DO MUCH
FOR THE KIDNEY DISEASE BUT WE
CAN REDUCE THE CARDIOVASCULAR
RISK THAT COMES WITH IT
 REDUCING THE C.V. RISK IN
THOSE WITH CKD
Reduce BP
Reduce proteinuria

Which antihypertensive in CKD?

ACEI / ARB if they have diabetes or
proteinuria. Then add diuretic, BB / CCB.
How to reduce proteinuria?
ARB, ACEI or Combination
 REDUCING THE C.V. RISK IN
THOSE WITH CKD
Increased serum phosphate predisposes to vascular
calcification and is now being recognised as a
cardiovascular risk factor.

Drugs used to reduce serum phosphate are

Calcium carbonate
Sevelamer
Lanthanum carbonate
 IS CALCIUM GOOD OR BAD IN
CKD?
Calcium is good because
It will reduce the increased PTH levels that cause bone disease
Serum calcium is low in patients with CKD

Calcium is bad because

Increased calcium predisposes to vascular calcification
(increase in the calcium - phosphorous product)
IS VITAMIN D GOOD FOR THOSE
WITH CKD?
The active form of vitamin D is needed to absorb calcium
from the intestines
There are vitamin D receptors in the nucleus of the cells
of the parathyroid gland. Stimulation of these receptors
results in lower PTH secretion

Vitamin D is given as:

Calcitriol
Alphacalcidol
Paricalcitol (NEW)
 DO THOSE WITH CKD BENEFIT
FROM STATINS?
The CARDS study (Lancet, 2004) showed
that treating diabetics with an additional
risk factor like hypertension or proteinuria
with atorvastatin reduced CV risk.

A Dutch study called the 4 D study (NEJM,

2005) showed that treating patients on
hemodialysis with atorvastatin did not
reduce CV risk.
 A PRESCRIPTION FOR CKD
Control BP to 125/75 with ACEI or ARB, but keep a watch on the
serum potassium.
Try to increase ACEI or ARB so that BP is well controlled as well as
proteinuria is reduced.
Use a statin to keep the LDL cholesterol at 2.6mmol (100mg) or less
Use a diuretic if there is edema. But remember, better to have a little
edema than to be too dry.
Calcium Carbonate 1.5 to 2 grams per day plus Calcitriol 0.25
micrograms daily (can increase to max of 1microgram daily). Watch
serum calcium and serum phosphorus.
Restrict fluids according to urine output. Rule of thumb is urine
output plus 500ml per day
 A PRESCRIPTION .
Iron needed if serum iron / Ferritin is low. Erythropoietin needed if
serum iron normal but patient is anemic (E. alpha given as 50 units
per kg IV slowly twice or thrice a week)

Vitamin B supplements including folic acid.

Hepatitis B immunisation (double dose needed)

Protein content of diet to be around 0.8gm per kg per day (not

necessary in ESRD patients on dialysis)
Check serum PTH levels once a year
 WHAT IS NEW?
In 2006, researchers are working on the
hypothesis that reduced levels of vitamin
D receptors are associated with increased
renin, increased angiotensin and
increased CV risk.
The increased CV risk in CKD may be partly
explained by the lower levels of active
vitamin D in these patients.
 TARGET HEMOGLOBIN IN CKD
The Normal Hematocrit Study looked at the use of Erythropoietin
alpha to maintain a hematocrit of 30 percent against that of 42
percent for patients with ESRD and CVD. The study was stopped
early because of increased mortality in the higher hematocrit group.
NEJM 1998
The CREATE trial looked at patients with CKD treated with
Erythropoietin beta to a target Hb level of 11.5 to 13.5 versus 10.5 to
11.5. The study found more cardiovascular events in the higher
hemoglobin group.
NEJM 2006
The CHOIR trial looked at anemia correction in patients with CKD
and found that those whose hemoglobin was corrected to 11.3gm/dL
had less CV events than those whose hemoglobin was corrected to
13.5gm/dL.
NEJM 2006
 HEMODIALYSIS
Maintenance Hemodialysis helps to prolong life in
chronic kidney disease. However it cannot replace all the
functions of the kidney.

Data from the USA tell us that only about 35 percent of

people on thrice weekly hemodialysis survive five years.
 DIALYSIS AND HEMOFILTATION

Hemofiltration helps to remove more fluid and

larger solutes
 ACUTE versus CHRONIC
RENAL INJURY
ACUTE RENAL INJURY is recognised by a significant
elevation of serum creatinine within hours or days or by a
significant decrease in urine output for more than 6
hours.
Elevation of serum creatinine by more than 26.5mmol/L or 0.3mg/dL.
Elevation of serum creatinine by more than 50 percent of baseline
Urine output less than 0.5ml per kg body weight

CHRONIC RENAL INJURY is recognised by the

presence of structural kidney damage or a decreased
GFR of less than 60ml/min per 1.73 square meter body
surface area for more than 3 months.
 ACUTE RENAL INJURY
Can be due to different causes:
Pre renal
Renal
Post renal

A good way to distinguish pre-renal from renal causes is to

look at the FRACTIONAL EXCRETION OF SODIUM.
Urine sodium divided by Plasma sodium Multiplied by 100
Urine creatinine divided by Plasma creatinine
A value more than 1 percent suggests a renal cause
 A QUIZ
A 38 year old man presents with the following report:
Blood urea 9.4mmol/L
Serum Na 136mmol/L
Serum K 4mmol/L
Serum creatinine 186umol/L.
As he also has diarrhoea for the past three days, you are not sure whether the
elevated urea and creatinine represent renal hypoperfusion or established
acute renal injury. So you order for urine sodium and urine creatinine.
His urine sodium is 21mmol/L and his urine creatinine is 1820umol/L.

Has he suffered acute renal injury or not?

The fractional excretion of sodium is more than
1 percent. He has suffered acute renal injury.
The elevated urea and creatinine are not
simply due to hypoperfusion but due to
established renal injury.
THANK
YOU