RFT creatinine clearance test (1)

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CLEARANCE TESTS AND SIGNIFICANCE

• M.PRASAD NAIDU
• Msc Medical Biochemistry,
• Ph.D Research scholar.

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FUNCTIONS OF KIDNEY

• REMOVES WASTE PRODUCTS
• REMOVES FOREIGN AND NON ENDOGENOUS
  SUBSTANCES
• MAINTAINS ELECTROLYTES AND WATER
• MAINTAINS ACIDBASE BALANCE
• HORMONAL FUNCTIONS

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FORMATION OF URINE

• NEPHRON----FUNCTIONAL UNIT OF KIDNEY
• NEPHRON CONTAINS
• a)GLOMERULUS
• b)TUBULES
• 1000 to 2000 ml of urine is excreted/day

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1)STEPS IN
URINE FORMATION Glomerular
filtration tubular reabsorption tubular
secretion
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GLOMERULAR FILTRATION

• 700ml of plasma passes through kidneys per
  minute.
• From this 120 to125 ml is filtered per/minute by
  kidneys.
• THIS IS GFR.

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GFR DECREASES

• GFR DECREASES IN
• OCCLUSION OF AFFERENT ARTERIOLES
• DECREASED PERMEABILITY OF THE MEMBRANE.
• INCREASED INTRA CAPSULAR PRESSURE

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GFR INCREASES IN

1. INCRESED BP
2. DECREASED BLOOD PROTEIN OSMATIC PRESSURE
3. INCRESED GLOMERULAR PERMEABILITY

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Effective filtration pressure

• Is the result of
• A)The glomerular pressure
  in glomerular capillaries
• B)The opposing osmotic
  pressure of plasma proteinsHydrostatic
  pressure of Bowmens capsule fluid
• Capillary pressure75 mmHg
• Osmatic pressure of plasmproteins30mmHg

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Net effective filtration pressure

• PefPg-(PppPbc) 75-(3020)
• Pef25mmHg
• Pghydrostatic pressure in the glomerular
  capillaries
• Ppposmotic pressure of plasma proteins
• Pbchydrostatic pressure of the bowmans capsule
  fluid

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RATE OF FILTRATION IS INFLUENCED BY

• Variation in BP in glomerular cappilary
• Concentration of plasma proteins
• Factors altering intratubular pressure viz.
• a) rise with ureteral obstruction
• b) during osmotic diuresis
• c) state of blood vessels

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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 and
• The effective glomerular filtration pressure
• In normal circumastances 700ml of plasma flow
  through the kidneys per minute 120 to125ml of
  fluid is filtered in to bowmans capsule

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Volume of filtrate reduced in extra renal
conditions

• 1.Dehydartion
• 2.Oligemic shock
• 3.Cardiac failure
• 4.lower the glomerular filtration pressure

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• 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 SECRETION
• Examples of substances secreted by the tubular
  epithelium are creatininepotassium

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RENAL FUNCTION TESTS

• 1.TEST BASED ON GLOMERULAR FILTRATION
• Urea clearance test
• Endogenous creatinine clearance test
• Inulin clearance test
• Cr51-EDTA clearance test

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2.TESTS TO MEASURE RENAL PLASM FLOW

• Para-amino hippurate test(PAH)
• Filtration fraction
• 3.TESTS BASED ON TUBULAR FUNCTION
• --Concentration and Dilution tests
• --15 minute-PSP excretion test
• --Measurement of tubular secretory mass
• MISCELANEOUS TESTS Can determine size, shape,
  any
• Tumour, obstuction, Infarct etc.

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CLEARANCE TESTS

• CLEARANCEDEFINED AS A VOLUME OF BLOOD OR PLASMA
  WHICH CONTAINS THEAMOUNT OF THE SUBSTANCE WHICH
  IS EXCRETED IN THE URINE OR
• THE CLEARANCE OF SUBSTANCE MAY BE DEFINED AS THE
  VOLUME OF BLOOD OR PLASMA CLEARED OF THE
  SUBSTANCE FOUND IN ONE MINUTE EXCRETION OF URINE

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SALIENT FEATURES OF SUBSTANCE USED FOR CLEARANCE
TESTS

1. It must be non toxic
2. It should be small enough to pass through the
   glomerular membrane
3. It should neither be secreted nor be absorbed by
   renal tubules
4. It should not be metabolised in the body

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CREATININE CLEARANCE

• CREATININE 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 1440
• REF.RANGE Male125ml/mt
• Female115ml/mt
• A decresed creatinine clearance is very sensitive
  indicator of a reduced glomerular filtration
  rate, due to acute or chronic damage.

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CREATININE

• The 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.

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CREATININE

• CREATININEREF.RANGE800---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.

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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 estimated

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RISKS OF THE PROCEDURE

• 24 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 following
• Forgetting to collect some of urine
• Going beyond 24 hour collection period and
  collecting excess urine
• Losing urine from specimen container through
  spilling
• Not keeping urine cold during collection period
• Acute stress
• Vigorous exercise

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PATIENT EDUCATION

• The accuracy of the test results depends on the
  accuracy of the specimen collection
• Collect in a clean environment
• It is important that dust from clothing not
  contribute to the specimen content
• Do not collect urine in metal glass containers
• Females Do not collect urine while menstruating

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PATIENT INSTRUCTIONS

• CAUTION 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 bottle
• Keep the bottle upright so it does not spill
• Do not urinate directly in to the bottle
• Keep out of reach of children
• If liquid in the bottle is spilled or splashed,
  wash immediately.

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PATIENT INSTRUCTIONS

• Record 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
  requisition
• Deliver the container and lab requisition to the
  laboratory immediately the collection is finished.

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PRESERVATIVES

• Preservatives to be added to 24 hour urine
  collection for various biochemical estimation
• Amylase, sodium, potassium and chloride-----------
  --- no preservative
• C peptide, cortisol, lead and zinc----------------
  --------- no preservative
• Protein and citrate------- no preservative
• Uric acid--------- no preservative

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PRESERVATIVES

• Calcium,phosphorous---10ml 6N HCL
• VMA,OXALATE-----------10ml 6N HCL
• CREATININE,UREA------10ml 6N HCL
• PROTEIEN AND CREATININE-----------
• ---10ml 6N HCL

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CREATININE CLEARANCE

• This is covenient method sensitive indicator for
  GFR
• ADVANTAGE OF CREATININE CLEARANCE
• A)It is a normal metabolite of the body
• B)It does not require I.V. administration
• C)Estimation of creatinine is simple
• D)In early stages it has got advantage over
  S.Creatinine
• CR.CLEARANCEUV/P
• In the calculation surface area is important
• Body surface area is calculated from
• LogA0.425 LogW0.725 LogH -2.144

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CREATININE CLEARANCE

• This is covenient method sensitive indicator for
  GFR
• ADVANTAGE OF CREATININE CLEARANCE
• A)It is a normal metabolite of the body
• B)It does not require I.V. administration
• C)Estimation of creatinine is simple
• D)In early stages it has got advantage over
  S.Creatinine
• CR.CLEARANCEUV/P
• In the calculation surface area is important
• Body surface area is calculated from

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LogA0.425 Log SW0.725 log H-2.144
ABody surface area in meter squareWWeight in
Kg
HHeight in cm

• Standard body surface area is 1.73 m²
• Creatinine clearance corrected for body surface
  area
• Calculated as
• UxV x 1.73/PxA
• Male normal value125 ml/mt
• Female normal value115 ml/mt

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A rough estimate of Creatinine clearancein
Males(140-Age) x Wt in Kg/72 xPcr

• C cr in Females0.85 xCcr
• CREATININE COEFFICIENTURINARY CREATININE
• EXPRESSED IN mg/kg body weight
• Normal range in Males 20 to 28mg/kg
• Females 15 to 21mg/kg
• Factor for converting mg/kg/ to nmol/kg/0.00884
• Value increses in Muscular Dystrophy

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P/C RATIO

• Creatinine estimation is also useful in the
  muscular dystrophy and in Nephrotic syndrome.
• P/C RATIOprotein concentration in mg/dl
• ___________________________________
• creatinine concentration in mg/dl
• p/c ratio ref.rangelt 1
• P/C ratio increases in NEPHROTIC SYNDROME

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M/C RATIO

• MC RATIOmg of micro albumin/gms of creatinine
• AS PER AMERICAN DIABETIC ASSOCIATION
• NORMAL VALUE IS LESS THAN 30 mg of uma/gm
  creatinine
• Abnormal 30 to 299 Microalbuminemia
• More than 300 Maacroalbuminemia

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INULIN 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.CUV/P ml/mt
• Uconcentration of inulin in urine in mg/dl
• Vvolume(ml) of urine passed /mt
• Pconcentration of inulin in plasma in mg/dl
• I.C125ml i.e GFR125ml
• Similar clearance value is seen with
  MANNITOL,SORBITOLDULCITOL

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INULIN CLEARENCE DECRESES IN

• Decrease in renal flow
• Obliteration or decrese in number of functioning
  glomeruli
• Defect in the effective glomerular filtration
  pressure
• Used to know the substance reabsorbed
• Urea reabsorbed in tubulesI.C-UREA CLEARANCE
• 
  -----------------------------
• 
  I.C
• 125-75
• -------0.4 SO,40 OF UREA REABSORBED
• 125

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UREA CLEARANCE

• Maximum clearance If the urine volume exceeds
  2 ml/mt.
• Volume of blood cleared of urea/mtUV/P 1000 X
  2.1/2875
• Standered clearancewhen the urinary volume is
  less than 2ml/mt
• CsUx square root of vV/P54 ml
• Only 60 of glomelular filtrate urea excreted
• Urea clearance is 60 of Inulin clearance
  UC/0.6I.C

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Determination of CR51 EDTA CLEARANCE

• SINGLE INJECTION IS USED FOR GFR ESTIMATION
• USED FOR CHILDREN ADULTS
• CONVENIENT FOR CHILDREN WHERE IT IS NOT EASY TO
  COLLECT 24 HOUR URINE.

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