Renal
function tests
Content
• Various
renal function tests
• Normal
reference ranges of various lab parameters
• Disease
conditions correlated with renal function tests
Objective
After completion of this lecture, student will be able
to:
• Explain
the various Renal function tests
• Explain
the normal reference ranges of various lab parameters
• Explain
the various disease conditions correlated with Renal function tests
Renal function tests
• 1200ml/min
– renal blood flow
• 625
ml/min reanl plasma flow
• 20%
of 625ml i.e 125ml/min is filtered
• Therefore
180L/ day is filtered
• But
1.5L is excreted as urine (99% is reabsorbed)
Introduction
Tests that estimate GFR use
– Endogenous markers
– Urea and
creatinine
– Exogenous markers
– Inulin, EDTA,
diethylenetriamine penta acetic acid
• Ideal
marker should undergo:
– Complete filtration
– No secretion
– No reabsorption
• 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
Exogenous markers
Inulin clearance
Normal range: men = 127mL/min/m2
Women = 118mL/min/m2
• Inulin
test is considered to be ‘gold standard’ for determining renal function.
• It
is neither secreted nor reabsorbed
Limitations
- Invasive (IV)
- Special
analytical methods
Iothalamate and EDTA clearance
Normal range: men = 127mL/min/m2
Women = 118mL/min/m2
I-Iothalamate
• Used
in research settiing
• Radioactive
Limitations
• Invasive
• Costly
• Timed
urine collections
EDTA clerance
• used as alternative for Iothalamte
Limitations
• invasive
• Timed urine collections
Endogenous markers
Cystatin C
• Cystatin
C is a protein that is produced by the cells in your body.
• When
kidneys are working well, they keep the level of cystatin C in your blood just
right.
• If
the level of cystatin C in your blood is too high, it may mean that your
kidneys are not working well
• A
cystatin C test may be used as an alternative
to creatinine and creatinine clearance
• It
is most useful in special cases where creatinine measurement could be
misleading.
• For
example, in those who have liver cirrhosis, are very obese,
are malnourished, practice a vegetarian diet, have amputated limbs, or
have reduced muscle mass (elderly and children), creatinine measurements may
not be reliable.
• Since
creatinine depends on muscle mass, assessment of kidney function may therefore
not be accurate in these individuals with abnormally high or low body mass.
• Cystatin
C is not affected by body mass or diet, and hence is a more reliable marker of
kidney function than creatinine.
Measurement of plasma creatinine
• Creatine
is the precursor of the creatinine
• It
is synthesized in liver – poured into blood – picked up by skeletal muscle –
stored as, creatine 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 creatinine, 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, triampterene, amiloride, spironolactone, trimethoprim, probencid,
aspirin inhibit the tubular secretion of creatinine. 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 cord 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
• Creatinine
is also effected by sex, low- protein diet and method of laboratory analysis.
• 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
Laboratory measurement
Laboratory measurement and reporting of serum creatinine
• Jaffes
test – most commonly
used method
• Inorganic
enzymatic method
• HPLC
Causes of falsely increased creatinine
• Increase
in glucose of 100mg/dL will elevate Scr by 0.5mg/dL (Similarly – ketones)
• Bilirubin
will falsely lower Scr levels
• Modified
Jaffe assays improved specificity
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]
• Urea
reabsorption tends to change in parallel with sodium, chloride and water
reabsorption
• Since
patients with volume depletion avidly reabsorb sodium, chloride and water,
larger amounts of urea is absorbed
• 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
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
• Usually,
BUN: Scr ratio greater than 20:1 suggest pre renal causes ( dehydration, blood
loss, shock, HF )
• 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
Renal plasma clearance
• 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
• Clearance
is expressed in ml / minute / 1.73 m2
• Can
be calculated from:
• Estimating
creatinine clearance from urinary creatinine
Renal clearance = UV / P X 1.73 / BSA
U- Concentration
of substance in urine (mg/ml)
P – Concentration
of substance in plasma
V – Urine
flow rate (ml/minute)
BSA –
body surface area
• Clearance
depends on three process:
a) Filtration b) Reabsorption
c) 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
CLCr (ml/minute) = [140-age] X body weight (Kg) / 7.2 X Secr
(mg/dl)
In case of female, the value is multiplied by 0.85
Summary
• Clinicians
should determine whether the actual GFR (inulin clearance) or surrogate
clearance (any substance other than inulin) would give the most useful
information
• BUN
test can be used to monitor hydrational status, renal function, protein
tolerance and catabolism in numerous clinical settings
• Patients
with GI bleeding and renal insufficiency, both BUN and Scr increases
• The ratio of at least 36 suggest GI bleeding
