CLEARANCE TESTS AND SIGNIFICANCE

CLEARANCE TESTS AND SIGNIFICANCEM.PRASAD NAIDUMsc Medical Biochemistry,Ph.D Research scholar.

FUNCTIONS OF KIDNEY

REMOVES WASTE PRODUCTS REMOVES FOREIGN AND NON ENDOGENOUS SUBSTANCES MAINTAINS ELECTROLYTES AND WATERMAINTAINS ACIDBASE BALANCEHORMONAL FUNCTIONS2

FORMATION OF URINENEPHRON----FUNCTIONAL UNIT OF KIDNEYNEPHRON CONTAINS a)GLOMERULUS b)TUBULES

1000 to 2000 ml of urine is excreted/day

1)STEPS IN URINE FORMATION Glomerular filtration tubular reabsorption tubular secretionGLOMERULAR FILTRATION700ml of plasma passes through kidneys per minute.

From this 120 to125 ml is filtered per/minute by kidneys.

THIS IS GFR.GFR DECREASES

GFR DECREASES IN OCCLUSION OF AFFERENT ARTERIOLES

DECREASED PERMEABILITY OF THE MEMBRANE. INCREASED INTRA CAPSULAR PRESSUREGFR INCREASES IN

INCRESED BPDECREASED BLOOD PROTEIN OSMATIC PRESSUREINCRESED GLOMERULAR PERMEABILITYEffective filtration pressureIs the result of A)The glomerular pressure in glomerular capillaries B)The opposing osmotic pressure of plasma proteins&Hydrostatic pressure of Bowmens capsule fluid Capillary pressure=75 mmHgOsmatic pressure of plasmproteins=30mmHg

Net effective filtration pressurePef=Pg-(Ppp+Pbc) = 75-(30+20) Pef=25mmHgPg=hydrostatic pressure in the glomerular capillariesPpp=osmotic pressure of plasma proteinsPbc=hydrostatic pressure of the bowmans capsule fluidRATE OF FILTRATION IS INFLUENCED BY Variation in BP in glomerular cappilaryConcentration of plasma proteinsFactors altering intratubular pressure viz. a) rise with ureteral obstruction b) during osmotic diuresis c) state of blood vessels THE VOLUME OF GLOMERULAR FILTRATE FORMED DEPENDS ON:The number of glomeruli functioning at a time,The volume of blood passing through the glomeruli per minute andThe effective glomerular filtration pressureIn normal circumastances 700ml of plasma flow through the kidneys per minute& 120 to125ml of fluid is filtered in to bowmans capsule

Volume of filtrate reduced in extra renal conditions1.Dehydartion2.Oligemic shock3.Cardiac failure4.lower the glomerular filtration pressure

TUBULAR REABSORPTION Formation of primary urine is 120 to 125 ml/mt.Only 1 to 2ml/mt reaches the bldder,170 litres of water filtered through the glomeruli &only 1.5 litre is excreted in the urine. So,99% glomerular filtrate is reabsorbed in the tubules

TUBULAR SECRETIONExamples of substances secreted by the tubular epithelium are creatinine&potassiumRENAL FUNCTION TESTS1.TEST BASED ON GLOMERULAR FILTRATION:Urea clearance test Endogenous creatinine clearance test Inulin clearance test Cr51-EDTA clearance test

2.TESTS TO MEASURE RENAL PLASM FLOWPara-amino hippurate test(PAH)Filtration fraction3.TESTS BASED ON TUBULAR FUNCTION: --Concentration and Dilution tests --15 minute-PSP excretion test --Measurement of tubular secretory massMISCELANEOUS TESTS; Can determine size, shape, anyTumour, obstuction, Infarct etc.CLEARANCE TESTSCLEARANCE;DEFINED AS A VOLUME OF BLOOD OR PLASMA WHICH CONTAINS THEAMOUNT OF THE SUBSTANCE WHICH IS EXCRETED IN THE URINE ORTHE CLEARANCE OF SUBSTANCE MAY BE DEFINED AS THE VOLUME OF BLOOD OR PLASMA CLEARED OF THE SUBSTANCE FOUND IN ONE MINUTE EXCRETION OF URINESALIENT FEATURES OF SUBSTANCE USED FOR CLEARANCE TESTSIt must be non toxicIt should be small enough to pass through the glomerular membraneIt should neither be secreted nor be absorbed by renal tubulesIt should not be metabolised in the bodyCREATININE CLEARANCECREATININE CLEARANCE: Useful in the diagnosis and prognosis of the kidney disease.CREATININE CLEARANCE=Urine creatinine in mg/dl x Total volume of urine___________________________________Serum creatinine in mg/dl x 1440REF.RANGE: Male:125ml/mtFemale:115ml/mtA decresed creatinine clearance is very sensitive indicator of a reduced glomerular filtration rate, due to acute or chronic damage.CREATININEThe kidney reserve is such that only when about 50% kidney function must be lost before creatinine level in blood is raised.But serum creatinine minor change in concentration may be of significance, and the serum level usually parallel to the severity of the disease.CREATININE CREATININE:REF.RANGE:800---2000mg/day.Creatinine is a waste product formed from Creatinine phosphate which is stored form of the energy in muscle. this conversion is spontaneous, non enzymatic process and is dependant on total muscle mass and this mass is not affected by diet,age,sex or exercise.Since the production is continuous and it is not affected by other factors thats why Creatinine is an ideal substance for clearance test. This test is mainly to assess the glomerular filtration. GFR provides the most useful index for the assessment of the severity of renal disease.24 hour urine collection

A 24 hour urine collection is a simple diagnostic procedure that measures the components of urine. The test is cheap, sensitive and is used to assess kidney function, hormones other substances can also be estimatedRISKS OF THE PROCEDURE24 hour urine collection is a safe, noninvasive procedure that is usually done without direct assistance.Certain factors or conditions may interfere with the accuracy of a 24 hour urine collection, include the followingForgetting to collect some of urineGoing beyond 24 hour collection period and collecting excess urineLosing urine from specimen container through spillingNot keeping urine cold during collection periodAcute stressVigorous exercisePATIENT EDUCATION:The accuracy of the test results depends on the accuracy of the specimen collectionCollect in a clean environmentIt is important that dust from clothing not contribute to the specimen contentDo not collect urine in metal glass containersFemales: Do not collect urine while menstruatingPATIENT INSTRUCTIONSCAUTION: The collection bottle may contain a preservative in the form of tablets or strong acid solution which may burn your skin.Do not remove preservative from the bottleKeep the bottle upright so it does not spillDo not urinate directly in to the bottleKeep out of reach of childrenIf liquid in the bottle is spilled or splashed, wash immediately.PATIENT INSTRUCTIONSRecord the time and date on the collection container label as the START TIME AND DATE. Also record the time and date in the FINISH TIME/DATE--------space provided on the laboratory requisitionDeliver the container and lab requisition to the laboratory immediately the collection is finished.PRESERVATIVESPreservatives to be added to 24 hour urine collection for various biochemical estimationAmylase, sodium, potassium and chloride-------------- no preservativeC peptide, cortisol, lead and zinc------------------------- no preservativeProtein and citrate------- no preservativeUric acid--------- no preservativePRESERVATIVESCalcium,phosphorous---10ml 6N HCLVMA,OXALATE-----------10ml 6N HCLCREATININE,UREA------10ml 6N HCL PROTEIEN AND CREATININE--------------10ml 6N HCL CREATININE CLEARANCEThis is covenient method &sensitive indicator for GFRADVANTAGE OF CREATININE CLEARANCE;A)It is a normal metabolite of the bodyB)It does not require I.V. administrationC)Estimation of creatinine is simpleD)In early stages it has got advantage over S.CreatinineCR.CLEARANCE=UV/PIn the calculation surface area is importantBody surface area is calculated fromLogA=0.425 LogW+0.725 LogH -2.144CREATININE CLEARANCEThis is covenient method &sensitive indicator for GFRADVANTAGE OF CREATININE CLEARANCE;A)It is a normal metabolite of the bodyB)It does not require I.V. administrationC)Estimation of creatinine is simpleD)In early stages it has got advantage over S.CreatinineCR.CLEARANCE=UV/PIn the calculation surface area is importantBody surface area is calculated from

32 LogA=0.425 Log SW+0.725 log H-2.144 A=Body surface area in meter squareW=Weight in Kg H=Height in cmStandard body surface area is 1.73 mCreatinine clearance corrected for body surface area Calculated asUxV x 1.73/PxAMale normal value=125 ml/mtFemale normal value=115 ml/mt

A rough estimate of Creatinine clearancein Males=(140-Age) x Wt in Kg/72 xPcrC cr in Females=0.85 xCcrCREATININE COEFFICIENT=URINARY CREATININE EXPRESSED IN mg/kg body weightNormal range in Males 20 to 28mg/kg Females 15 to 21mg/kgFactor for converting mg/kg/ to nmol/kg/=0.00884Value increses in Muscular DystrophyP/C RATIOCreatinine estimation is also useful in the muscular dystrophy and in Nephrotic syndrome.P/C RATIO=protein concentration in mg/dl___________________________________ creatinine concentration in mg/dlp/c ratio ref.range=< 1P/C ratio increases in NEPHROTIC SYNDROME

M/C RATIOMC RATIO=mg of micro albumin/gms of creatinineAS PER AMERICAN DIABETIC ASSOCIATIONNORMAL VALUE IS LESS THAN 30 mg of uma/gm creatinineAbnormal 30 to 299 MicroalbuminemiaMore than 300 MaacroalbuminemiaINULIN CLEARANCE 10 gm of Inulin is dissolved in 100ml of saline is injected I.V at a rate of 1 ml/mt over 2 hours I.C=UV/P ml/mtU=concentration of inulin in urine in mg/dlV=volume(ml) of urine passed /mtP=concentration of inulin in plasma in mg/dlI.C=125ml i.e GFR=125mlSimilar clearance value is seen with MANNITOL,SORBITOL&DULCITOLINULIN CLEARENCE DECRESES IN

Decrease in renal flowObliteration or decrese in number of functioning glomeruliDefect in the effective glomerular filtration pressureUsed to know the substance reabsorbedUrea reabsorbed in tubules=I.C-UREA CLEARANCE ----------------------------- I.C 125-75-------=0.4 SO,40% OF UREA REABSORBED 125 UREA CLEARANCEMaximum clearance; If the urine volume exceeds 2 ml/mt.Volume of blood cleared of urea/mt=UV/P =1000 X 2.1/28=75Standered clearance;when the urinary volume is less than 2ml/mtCs=Ux square root of V/P=54 mlOnly 60% of glomelular filtrate urea excretedUrea clearance is 60% of Inulin clearance =UC/0.6=I.C

Determination of CR EDTA CLEARANCESINGLE INJECTION IS USED FOR GFR ESTIMATIONUSED FOR CHILDREN &ADULTSCONVENIENT FOR CHILDREN WHERE IT IS NOT EASY TO COLLECT 24 HOUR URINE.THANK YOU