Glomerular Filtration Rate. Hui Li, PhD, FCACB, DABCC

Glomerular Filtration Rate Hui Li, PhD, FCACB, DABCC

Glomerular Filtration Rate (GFR): Amount of blood that is filtered per unit time through glomeruli. It is a measure of the function of kidneys. The Concept of Clearance of a substance: the volume of plasma from which the substance is completely cleared by the kidneys per unit of time. Afferent arteriole Bowman s capsule Secreted Efferent arteriole Glomerulus Filtered freely (small size) Reabsorbed Filtered S = Excreted S GFR Ps = Us V GFR=Us V/Ps

Measurement of GFR Exogenous Clearance Endogenous Serum markers Hierarchy Gold Standard Silver Standard Bronze standard Of uncertain clinical use Marker Inulin continuous infusion urinary clearance Inulin single bolus plasma clearance 51 Cr-EDTA 99m Tc-DTPA 125 I-iothalamate Iohexol Creatinine Cystatin C Creatinine urinary clearance* Urea Retinol-binding protein 1-microglobulin 2-microglobulin Prostaglandin D synthase

Exogenous urinary/plasma clearance Advantages Designed to closely satisfy the criteria of an ideal marker of GFR Disadvantages Exogenous Time consuming Requires a timed urine/plasma collection Overestimation (plasma clearance) extrarenal clearance ignored distribution phase Radioisotopic

Endogenous Serum Markers Advantages Endogenous More convenient Less expensive Converted to GFR using formula Disadvantages Nonrenal influences on production rate Secretion/ Reabsorption in renal tubular cells.

Donadio et al., J Pharm Biomed Anal 23;32:199-14. 99m Tc-DTPA urinary clearance

Renal transplantation patients Children 99m Tc-DTPA PCl 51 Cr-EDTA 99m Tc-DTPA PCl Poge et al., Clin Chem 25;51:1531-33. Filler et al., Clin Chem 22;48:729-36.

Significantly higher than the other two 115 diabetic patients n=74, GFR>8ml min -1 n=41, GFR<8ml min -1 Inulin continuous infusion urinary clearance n=8, GFR>7ml min-1 1.73m-2 n=54, GFR<7ml min-1 1.73m-2 P=.14 Inulin continuous infusion urinary clearance P=.28 P=.62 Priem et al., Clin Chem 1999;45:567-8 Woitas et al., Clin Chem 21;47:2179-8

99m Tc-DTPA PCl in Ottawa 51 Cr-EDTA PCl in Berlin Significantly lower than the others Filler et al., Clin Chem 22;48:729-36.

83 Renal transplantation patients 99m Tc-DTPA plasma clearance No difference in AUC Poge et al., Clin Chem 25;51:1531-33.

Estimated glomerular filtration rate (egfr): an estimate of the GFR calculated from concentration of serum markers. GFR prediction equations using plasma creatinine concentration Cockroft-Gault (14 - age) weight/72 S cr (.85 if female) ml/min MDRD 1 17 (S cr /88.4 ) -.999 age -.176 (.762 if female) (1.18 if black) (S c 2.81) ml/min/1.73m 2 -.17 Alb +.318 MDRD 2 ml/min/1.73m 2 186 (S cr /88.4) -1.154 age -.23 (1.212 if black) (.742 if female) Schwartz.55 height (S cr /88.4) -1 ml/min Counahan-Barratt.43 height (S cr /88.4) -1 ml/min/1.73m 2 Height(cm), Weight(Kg), Scr( mol/l)

Cystatin C-based GFR prediction equation 536 patients:.3-96 years, 262 females and 274 males GFR: plasma iohexol clearance Without gender factor: GFR [ml min -1 (1.73m 2 ) -1 ] =84.69 cystatin C (mg/l) -1.68 [ 1.384 if child<14 years] With gender factor: GFR [ml min -1 (1.73m 2 ) -1 ] =87.62 cystatin C (mg/l) -1.693 [ 1.376 if child<14 years] [.94 if female] Clin Chem 25;51:142-31.

Clin Chem 25;51:142-31.

Clin Chem 25;51:142-31.

GFR measured in MSH Data Information For specimens received Jan 24 to Oct 25 Includes inpatients and outpatients Female (n=88), Male (n=317) Includes pregnant subjects Exclusions Urine Collected for <2 or >25.5 Hours Urine Creatinine <3 or >25 mmol/day Weight <34 or >146 Kg Height <11 or >193 cm Analytical method for serum, plasma and urine creatinine: Creatininase, creatinase, and sarcosine oxidase, with the liberated hydrogen peroxide tied to a colorimetric reaction.

Blood Creatinine / Creatinine Clearance (Non-normalized vs. Normalized to BSA) Body Surface Area Du Bois vs. Gehan George Blood Creatinine / Creatinine Clearance Female vs. Male Inverse Creatinine vs. egfr / Creatinine Clearance Inverse Creatinine vs. egfr / Creatinine Clearance GFR< 9ml min-1 1.73m-2

Blood Creatinine / Creatinine Clearance Non-normalized vs. Normalized Blood Creatinine (umol/l) 8 7 6 5 4 3 2 1 ALL (n=1125) y = 18.55x -.6896 R 2 =.668 2 4 6 Non-Normalized Creatinine Clearance (ml/s) Blood Creatinine (umol/l) 8 7 6 5 4 3 2 1 ALL (n=1125) y = 17.44x -.7488 R 2 =.741 2 4 6 Normalized Creatinine Clearance

Body Surface Area (Gehan & George, 197) [m^2] 3. 2.5 2. 1.5 1. Body Surface Area Du Bois vs. Gehan George Females (n=88) y = 1.1324x -.1665 R 2 =.9514 1. 1.5 2. 2.5 3. Body Surface Area (Du Bois, 1916) [m^2] Body Surface Area (Gehan & George, 197) [m^2] 3. 2.5 2. 1.5 1. Males (n=317) y = 1.789x -.1142 R 2 =.9469 1. 1.5 2. 2.5 3. Body Surface Area (Du Bois, 1916) [m^2] Blood Creatinine (umol/l) 8 7 6 5 4 3 2 1 ALL (n=1125) y = 17.44x -.7488 R 2 =.741 Blood Creatinine (umol/l) 8 7 6 5 4 3 2 1 ALL (n=1125) y = 14.99x -.7516 R 2 =.7352 2 4 6 Normalized Creatinine Clearance 2 4 6 GGNormalized Creatinine Clearance

Blood Creatinine / Creatinine Clearance Female vs. Male Blood Creatinine (umol/l) 8 7 6 5 4 3 2 1 y = 97.34x -.6991 R 2 =.7572 Females (n=88) 2 4 6 Normalized Creatinine Clearance Blood Creatinine (umol/l) 8 7 6 5 4 3 2 1 Males (n=317) y = 124.83x -.6647 R 2 =.6635 1 2 3 4 Normalized Creatinine Clearance 5

Inverse Creatinine vs. egfr / Creatinine Clearance Inverse Creatinine (L/umol) 5 45 4 35 3 25 2 15 1 5 ALL (n=1125) y = 9.378x.7488 R 2 =.741 2 4 6 8 Normalized Creatinine Clearance MDRD Predicted GFR (ml/min/1.73m^2) 5 45 4 35 3 25 2 15 1 5 ALL (n=1125) y = 56.629x.8583 R 2 =.7588 NormCockcroft-Gault 7 6 5 4 3 2 1 ALL (n=1125) y = 1.347x.9352 R 2 =.7591 2 4 6 Normalized Creatinine Clearance 1 2 3 4 5 6 7 Normalized Creatinine Clearance

Inverse Creatinine vs. egfr / Creatinine Clearance GFR< 9ml min-1 1.73m-2 Inverse Creatinine (L/umol) 4 35 ALL (n=352) 3 25 y = 9.3241x.788 R 2 =.575 2 15 1 5..4.8 1.2 1.6 Normalized Creatinine Clearance MDRD Predicted GFR (ml/min/1.73m^2) 3 25 2 15 1 5 ALL (n=352) y = 57.228x.9331 R 2 =.6147 NormCockcroft-Gault 5 4 3 2 1 ALL (n=352) y = 1.76x.963 R 2 =.5862..4.8 1.2 1.6 Normalized Creatinine Clearance..4.8 1.2 1.6 Normalized Creatinine Clearance

Conclusions Serum creatinine correlates better with BSA-normalized creatinine clearance than with unnormalized creatinine clearance The correlation between serum creatinine and BSAnormalized creatinine clearance is not affected by different methods used to calculate BSA (Du Bois/Gehan and George). Inverse serum creatinine, the estimated GFR using Cockcroft-Gault formula or MDRD formula yielded similar prediction of Creatinine Clearance.