RENAL CLEARANCERENAL CLEARANCE

Definition: Definition: Is the Is the volumevolume of plasma completely of plasma completely clearedcleared of a substance by the kidneys per of a substance by the kidneys per unit timeunit time. .

The The higherhigher the renal clearance, the the renal clearance, the more more plasma that is cleared of the substance.plasma that is cleared of the substance.

Unit: ml/minUnit: ml/min

Renal ClearanceRenal Clearance

Nephron Excretion & Clearance

Inulin A plant product that is filtered but not

reabsorbed or secreted

Used to determine

clearance rate and therefore

nephron function

NephronExcretion & Clearance

The relationship between clearance and excretion using a few examples

NephronExcretion & Clearance

CCxx = U = Uxx x V x V

PPxxWhereWhere x = substancex = substance

CCxx = clearance of substance = clearance of substance

UUxx = urine concentration of substance = urine concentration of substance

PPxx = plasma concentration of substance = plasma concentration of substance

V = urine flow rate (ml/min)V = urine flow rate (ml/min)

Amount of substance excreted = (filtered –Amount of substance excreted = (filtered –reabsorbed + secreted)reabsorbed + secreted)UUxx V = GFR x P V = GFR x Pxx ± T ± Txx

Equation for renal clearanceEquation for renal clearance

Comparison of clearance of a substance Comparison of clearance of a substance with clearance of inulinwith clearance of inulin

1) 1) = inulin = inulin clearance; only filtered not clearance; only filtered not reabsorbedreabsorbed or or secretedsecreted

2) 2) < inulin < inulin clearance; clearance; reabsorbedreabsorbed by nephron by nephron tubulestubules

3) 3) > inulin > inulin clearance; clearance; secretedsecreted by nephron by nephron tubulestubules

PAHPAH (585 ml/min)(585 ml/min)

Inulin (125 ml/min)Inulin (125 ml/min)

Urea (40 ml/min)Urea (40 ml/min)

Glucose (0)Glucose (0)

100 200 300 400 500 600100 200 300 400 500 600

Clearance (ml/min)Clearance (ml/min)

Examples: clearance of known substancesExamples: clearance of known substances

Application of renal clearance Application of renal clearance in kidney functionin kidney function

Inulin clearance can be used to estimate Inulin clearance can be used to estimate GFRGFR (by calculation)(by calculation)

PAH clearance can be used to estimate renal PAH clearance can be used to estimate renal plasma flow plasma flow

Measurement of filtration fraction = GFR / RPFMeasurement of filtration fraction = GFR / RPF

Measurement of creatinine clearance Measurement of creatinine clearance

GFR x PGFR x PSS = U = USS x V x V

GFR = UGFR = Uss x V = C x V = Css

PPss

If a substance is freely filtered and not If a substance is freely filtered and not reabsorbed or secreted reabsorbed or secreted rate of excretion in rate of excretion in urine is equal to rate of substance filtered by urine is equal to rate of substance filtered by kidney. Thus,kidney. Thus,

Inulin clearanceInulin clearance

GFR therefore, can be calculated as follows:GFR therefore, can be calculated as follows:

Inulin, a polysaccharide molecule with MW of Inulin, a polysaccharide molecule with MW of 5200, fits these criteria.5200, fits these criteria.

INULIN CLEARANCEINULIN CLEARANCE

GFR = CGFR = Cinin = 125ml/min = 125ml/min

CREATININE CLEARANCECREATININE CLEARANCE

CCcrcr = U = Ucrcr x V x V

PPcrcr

WhereWhere C Ccrcr = creatinine clearance = creatinine clearance

UUcrcr = urine concentration of creatinine = urine concentration of creatinine

PPcrcr = plasma concentration of creatinine = plasma concentration of creatinine

V = urine flow rate (ml/min)V = urine flow rate (ml/min)

Creatinine clearance overestimate GFR by 10-20% due to creatinine secretion in very small amounts.

Blood urea and creatinine will not be raised above normal range until 60% of total kidney function is lost.

Hence, the more accurate GFR or creatinine clearance is measured whenever renal disease is suspected or careful dosing of nephrotic drug is required.

Plasma creatinine:Plasma creatinine:(Normal plasma creatinine in daults = 0.6 – 1.2 mg/dl(Normal plasma creatinine in daults = 0.6 – 1.2 mg/dl))

Index of GFRIndex of GFR1616

1212

88

44

000 45 90 135 1800 45 90 135 180

Glomerular filtration rate (L/day)Glomerular filtration rate (L/day)

Pla

sma

crea

tin

ine

(mg

/dl)

Pla

sma

crea

tin

ine

(mg

/dl)

NormalNormal

Reduced reserveReduced reserve

Renal impairmentRenal impairment

End-stageEnd-stagerenal diseaserenal disease

200 400 600 800 1000 1200200 400 600 800 1000 1200

120120

100100

8080

6060

4040

2020

2.3 4.5 6.8 9.0 11.3 13.62.3 4.5 6.8 9.0 11.3 13.6

Plasma creatinine (µmol/L)Plasma creatinine (µmol/L)

Plasma creatinine (mg/dL)Plasma creatinine (mg/dL)G

FR

(m

L/m

in)

GF

R (

mL

/min

)

Relationship between serum creatinineRelationship between serum creatinineand renal functionand renal function

RPF = URPF = UPAHPAH x V = C x V = CPAHPAH

PPPAHPAH

If a substance is completely cleared from If a substance is completely cleared from plasma plasma clearance rate is equal to total clearance rate is equal to total renal plasma flow renal plasma flow amount delivered to amount delivered to kidneys is equal to amount excreted. Thus,kidneys is equal to amount excreted. Thus,

Para-aminohippuric acid (PAH) clearancePara-aminohippuric acid (PAH) clearance

Renal Blood FlowRenal Blood Flow

Resting condition (adult) receiveResting condition (adult) receive1.2 L/min (25% of CO)1.2 L/min (25% of CO)

Measurement of RBFMeasurement of RBFa)a) Electromagnetic flow metersElectromagnetic flow metersb)b) FickFick’s ’s principle principle

Fick PrincipleFick Principle• Amount taken up by an organ (kidney) per unit of Amount taken up by an organ (kidney) per unit of

time divided by the arterio-venous difference of the time divided by the arterio-venous difference of the substance = plasma flowsubstance = plasma flow

• RPF = amount of substance excreted divided by the RPF = amount of substance excreted divided by the renal arterio-venous difference.renal arterio-venous difference.

RPF = URPF = UPAHPAH x V x V

RARAPAHPAH – RV – RVPAH PAH

RVRVPAHPAH = 0, = 0,

RPF is described as RPF is described as effectiveeffective renal plasma flow renal plasma flow (ERPF).(ERPF).

Effective RPF (ERPF)Effective RPF (ERPF)

Effective RPF = UEffective RPF = UPAHPAH V V

PPPAHPAH

Where:Where:Effective RPF = effective renal plasma flow (ml/min)Effective RPF = effective renal plasma flow (ml/min)UUPAHPAH = urine concentration of PAH (mg/ml) = urine concentration of PAH (mg/ml)

V = urine flow rate (ml/min)V = urine flow rate (ml/min)PPPAHPAH = plasma concentration of PAH (mg/ml) = plasma concentration of PAH (mg/ml)

CCPAHPAH = clearance of PAH (ml/min) = clearance of PAH (ml/min)

Actual RPF Actual RPF = ERPF= ERPF Extraction ratioExtraction ratio

= 630 / 0.9 = = 630 / 0.9 = 700 ml/min700 ml/min

Effective RPF Effective RPF = U= UPAHPAH x V x V

PPPAHPAH

= 14 mg/ml x 0.9 ml/min= 14 mg/ml x 0.9 ml/min

0.02 mg/ml0.02 mg/ml

= 630 ml/min= 630 ml/min

The clearance of PAHA reflect only RPF to The clearance of PAHA reflect only RPF to portionsportions of the kidney of the kidney that that dealdeal with urine formation, and thus with urine formation, and thus underestimateunderestimate actual actual RPF by about 10%.RPF by about 10%.The renal extraction ratio of PAH = 0.92The renal extraction ratio of PAH = 0.92

Measuring renal blood flow (RBF)Measuring renal blood flow (RBF)

RBF is calculated from RPF and the RBF is calculated from RPF and the hematocrit (PCV). Formula is as follows:hematocrit (PCV). Formula is as follows:

RBF = RPFRBF = RPF RBF = 700RBF = 700

1 – Hct 1 – Hct 0.55 0.55 = 1273 ml/min= 1273 ml/min

Where:Where:RBF = renal blood flow (ml/min)RBF = renal blood flow (ml/min)RPF = renal plasma flow (ml/min)RPF = renal plasma flow (ml/min)PCV = hematocritPCV = hematocrit

Hematocrit (PCV) = 0.45Hematocrit (PCV) = 0.45

Glomerular Glomerular capillarycapillary

Bowman’s Bowman’s spacespace

UrineUrine UrineUrine UrineUrine

Substance Substance XX

Substance Substance YY

Substance Substance ZZ

Renal handling of hypothetical substance X, Y, Z.Renal handling of hypothetical substance X, Y, Z.X, filtered & secreted not reabsorbedX, filtered & secreted not reabsorbedY, filtered, fraction reabsorbedY, filtered, fraction reabsorbedZ, filtered, completely reabsorbedZ, filtered, completely reabsorbed