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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