Renal function tests (RFT)

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

  1.  Invasive (IV)

  2. 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

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