Renal Function Tests

Renal Function Tests
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Introduction
Tests that estimate GFR use
 Endogenous markers
- urea and creatinine
 Exogenous markers
- inulin, EDTA, diethylenetriamine penta acetic acid
Introduction
Ideal marker should undergo:
 Complete filtration
 No secretion
 No reabsorption
Introduction
 Tests for endogenous markers clearance correlate

roughly with the GFR, whereas test for exogenous
marker clearance provides much closer correlations
 Clinicians should determine whether the actual

GFR (inulin clearance) or surrogate clearance (any
substance other than inulin) would give the most
useful information
Introduction
 Inulin test is considered to be ‘gold standard’ for
determining renal function.
 Though it is considered as ‘gold standard’, CLcr

may yield better results for pharmacokinetic dosing,
since most kinetic studies use creatinine to estimate
drug clearance and to develop dosing strategies
Methods:
Blood urea nitrogen

Measurement of plasma creatinine
Renal plasma clearance
Blood Urea Nitrogen (BUN)
Normal range: 8 – 20 mg /dl or 2.9 - 7.1 mmol/L
It is the serum concentration of nitrogen (within

urea)
Serum concentration depends upon:

- filtration
- production (in liver)
- tubular reabsorption
Increase BUN may reflex decrease GFR
It is not the ideal GFR marker

[it undergoes tubular reabsorption to an extent of 50% of filtered urea]
BUN elevation seen in:
- high protein diet
[including AA infusion]
- upper GIT bleeding

[blood is digested as dietary proteins]
- administration drugs
[corticosteroids, tetracycline and drugs with anti
anabolic effect]
BUN reduction seen in:
- malnutrition
- profound liver damage
- fluid overload
BUN test can be used to monitor hydrational status, renal function,

protein tolerance and catabolism in numerous clinical settings
Creatine is the precursor of the creatinine
It is synthesized in liver – poured into blood –

picked up by skeletal muscle – stored as, creatinine
phosphate, high energy form
Creatine phosphate acts as a readily available

source of phosphorous for the production of ATP
Creatinine is an spontaneous decomposition

product of creatine and creatine phosphate
The daily production of creatinine is 2% of total
body creatine, which remains constant if muscle
mass is not changed significantly
Reference range:
Adults: 0.7 – 1.5 mg/dl
Children: 0.2 – 0.7 mg/dl
If the level rises above the reference range it is an

indication of poor renal function
However, clinicians should not depend solely on
serum creatinine because serum creatinine elevation
seen in
Dehydration
Renal dysfunction
Urinary tract obstruction
Excess catabolism
Excess exercise
Muscular dystrophy
Myasthenia gravis
Drugs [cimetidine, triamterene, amiloride, spiranolactone,
trimethoprim, probecid, aspirin inhibit the tubular secretion of creatine.
Although they may increase serum creatinine these increase are not
from a decreased GFR]
Moreover , since serum creatinine is by-product of

muscle metabolism, severely decreased muscle mass
or activity may be reflected by low serum creatinine
Thus patients with spinal card injuries and muscle

inactivity have decreased creatinine production
Conversely, very muscular patients occasionally

have slightly elevated serum creatinine with
elevated creatinine excretion and normal GFR
Therefore, as long as no abnormalities exist in

muscle mass, an increase serum creatinine almost
always reflects decrease GFR
The converse is always not true because a normal
serum creatinine does not necessarily imply a
normal GFR. As a part of aging process, both
muscle mass and renal function decline. Therefore,
serum creatinine remains normal range because as
the kidneys became less capable of filtering and
excreting creatinine
Thus clinicians should not rely solely on serum

creatinine as an index of renal function. They
should obtain or estimate the creatinine clearance
Concomitant serum BUN and
creatinine
Simultaneous BUN and serum creatinine can
furnish valuable information
In acute renal failure both are altered. However,

BUN : Scr ratio is often 20:1 or higher
Patients with GI bleeding and renal insufficiency,

both BUN and Scr increases. The ratio of at least 36
suggest GI bleeding
Concomitant serum BUN and
creatinine
Usually, BUN:Scr ratio greater than 20:1 suggest pre
renal causes
Ratios from 10:1 to 20:1 suggest intrinsic renal

damage
However, both types may occur simultaneously,

confounding typical interpretation. Furthermore, the
ratio greater than 20:1 is not clinically important if
the values of BUN and Scr under the reference range
Expresses how effectively the kidneys remove a
substance from blood plasma
High renal clearance – efficient removal of

substance from plasma into urine
Low renal clearance – less efficient removal of

substance from plasma into urine
CrClearance is expressed in ml / minute / each 1.73

m2 of the patients BSA.
Can be calculated from:
a) Estimating creatinine clearance from urinary

creatinine
UV 1.73
Renal clearance = X
P BSA
U- concentration of Creatinine in urine (mg/ml)

P – concentration of Creatinine in plasma
V – urine flow rate (ml/minute)
BSA – body surface area
Clearance depends on three process:
Filtration
Reabsorption
Secretion
If the substance is filtered and neither reabsorbed

nor secreted, then its clearance is equal to GFR
[E.g inulin (iv infusion) – GFR = 125 ml /minute]
If the substance is filtered and secreted but not

reabsorbed, then its clearance is more than GFR
[E.g creatinine – GFR = 140 ml / minute]
It is helpful to know the renal blood flow –

[Clearance of para amino hippuric acid (PAH) is equal to
the renal blood flow]
b) Estimating creatinine clearance without urine
collection
In clinical practice. CLCr is usually estimated from

the plasma creatinine concentration rather than
measured
The Cockcroft and Gault equation is widely used

which considers age, sex and body weight
[140-age] X body weight (Kg)

CLCr (ml/minute) =
7.2 X Scr (mg/dl)
In case of female, the value is multiplied by 0.85
If SI units are used (if expressed in micromol/L)
[150-age] X body weight (Kg)

CLCr (ml/minute) =
SCr (micromol/L)
In males : 10% is added to the value estimated
In females: 10% is subtracted from the value estimated
[1 mg / dl = 88.4 micromol/L] ; It gives similar results to previous equation

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Renal Function Tests

 Tests for endogenous markers clearance correlate

 Clinicians should determine whether the actual

 Though it is considered as ‘gold standard’, CLcr

Blood urea nitrogen

It is the serum concentration of nitrogen (within

Serum concentration depends upon:

Increase BUN may reflex decrease GFR

It is not the ideal GFR marker

- upper GIT bleeding

BUN test can be used to monitor hydrational status, renal function,

It is synthesized in liver – poured into blood –

Creatine phosphate acts as a readily available

Creatinine is an spontaneous decomposition

If the level rises above the reference range it is an

Moreover , since serum creatinine is by-product of

Thus patients with spinal card injuries and muscle

Conversely, very muscular patients occasionally

Therefore, as long as no abnormalities exist in

Thus clinicians should not rely solely on serum

In acute renal failure both are altered. However,

Patients with GI bleeding and renal insufficiency,

Ratios from 10:1 to 20:1 suggest intrinsic renal

However, both types may occur simultaneously,

High renal clearance – efficient removal of

Low renal clearance – less efficient removal of

CrClearance is expressed in ml / minute / each 1.73

a) Estimating creatinine clearance from urinary

U- concentration of Creatinine in urine (mg/ml)

If the substance is filtered and neither reabsorbed

If the substance is filtered and secreted but not

It is helpful to know the renal blood flow –

In clinical practice. CLCr is usually estimated from

The Cockcroft and Gault equation is widely used

[140-age] X body weight (Kg)

In case of female, the value is multiplied by 0.85

[150-age] X body weight (Kg)

In males : 10% is added to the value estimated

In females: 10% is subtracted from the value estimated

[1 mg / dl = 88.4 micromol/L] ; It gives similar results to previous equation

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