Background: Exogenous tracer-based methods of measuring glomerular filtration rate (GFR) are difficult to perform, whilst creatinine-based estimation formulae are inaccurate. Methods: We assessed a new technique of measuring iohexol clearance using timed dried capillary blood spots. A reference GFR was measured in 81 subjects (GFR 15–124 ml/min/1.73 m2) by iohexol clearance using three venous samples (2, 3 and 4 h after an intravenous bolus). GFR was estimated by six test methods; iohexol clearance using (i) 3 blood spots (2, 3, 4 h); (ii) 2 blood spots (2, 4 h) and (iii) 1 blood spot (4 h); (iv) the Modification of Diet in Renal Disease (MDRD) formula; (v) the Cockcroft-Gault formula, and (vi) a formula estimating GFR from serum cystatin C concentration. For each test method the bias and precision were calculated as the mean and standard deviation (SD) of the ‘GFR differences’ (test method GFR – reference GFR). Results: The limits of agreement (bias ±1.96 × SD; in ml/min/1.73 m2) were: (i) 1.1 ± 15.1 for 3-spot iohexol clearance; (ii) 0.6 ± 14.9 for 2-spot iohexol clearance; (iii) 4.5 ± 21.2 for 1-spot iohexol clearance; (iv) –15.7 ± 33.3 for the MDRD formula; (v) –9.6 ± 32.9 for the Cockcroft-Gault formula, and (vi) –12.1 ± 31.7 for the Cystatin C formula. The accuracy of all six test methods was similar among individuals with GFR <60 ml/min/ 1.73 m2; however, in individuals with GFR ≧60 ml/min/ 1.73 m2, the MDRD, Cockcroft-Gault and Cystatin C formulae were all imprecise and systematically underestimated GFR. Conclusions: Blood spot iohexol clearance provides a potentially practical method of estimating GFR accurately in large-scale epidemiological studies especially among individuals without established chronic kidney disease.

Keywords:
Creatinine, Calculated creatinine clearance, Glomerular filtration rate, Iohexol
1.
Levey AS, Bosch JP, Lewis JB, Greene T, Rogers N, Roth D: A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation. Ann Intern Med 1999;130:461–470.
2.
Levey AS, Greene T, Kesek JW, Beck GJ: A simplified equation to predict glomerular filtration rate from serum creatinine. J Am Soc Nephrol 2000;11(suppl):155.
3.
Cockcroft DW, Gault MH: Prediction of creatinine clearance from serum creatinine. Nephron 1976;16:31–41.
4.
Poggio ED, Wang X, Greene T, Van Lente F, Hall PM: Performance of the Modification of Diet in Renal Disease and Cockcroft-Gault equations in the estimation of GFR in health and in chronic kidney disease. J Am Soc Nephrol 2005;16:459–466.
5.
Rule AD, Larson TS, Bergstralh EJ, Slezak JM, Jacobsen SJ, Cosio FG: Using serum creatinine to estimate glomerular filtration rate: accuracy in good health and in chronic kidney disease. Ann Intern Med 2004;141:929–937.
6.
Dharnidharka V, Kwon C, Stevens G: Serum cystatin C is superior to serum creatinine as a marker of kidney function: a meta-analysis. Am J Kidney Dis 2002;40:221–226.
7.
Galteau MM, Guyon M, Gueguen R, Siest G: Determination of serum cystatin C: biological variation and reference values. Clin Chem Lab Med 2001;39:850–857.
8.
Hoek FJ, Kemperman FAW, Krediet RT: A comparison between cystatin C, plasma creatinine and the Cockcroft-Gault formula for the estimation of glomerular filtration rate. Nephrol Dial Transplant 2003;18:2024–2031.
9.
Nilsson-Ehle P: Iohexol clearance for the determination of glomerular filtration rate: 15 years’ experience in clinical practice. eJIFCC 2002;13:http://www.ifcc.org/ejifcc/vol13no2-1301200105.htm.
10.
Krutzen E, Back SE, Nilsson-Ehle I, Nilsson-Ehle P: Plasma clearance of a new contrast agent, iohexol: a method for the assessment of glomerular filtration rate. J Lab Clin Med 1984;104:955–961.
11.
D’Mello L, Niculescu I, Carr E, Barron LB, Kwan JT, Bending MR, Newman DJ: Development of an outpatient GFR procedure suitable for epidemiological investigations. J Am Soc Nephrol 2001;12(suppl):199.
12.
Du Bois D, Du Bois EF: A formula to estimate the approximate surface area if height and weight be known. Nutrition 1989;5:303–311.
13.
Jacobsson L: A method for the calculation of renal clearance based on a single plasma sample. Clin Physiol 1983;3:297–305.
14.
Chowdhury TA, Dyer PH, Bartlett WA, Legge ES, Durbin SM, Barnett AH, Bain SC: Glomerular filtration rate determination in diabetic patients using iohexol clearance – comparison of single and multiple plasma sampling methods. Clin Chim Acta 1998;277:153–158.
15.
Bland JM, Altman DG: Statistical methods for assessing agreement between two methods of clinical measurement. Lancet 1986;1:307–310.
16.
K/DOQI Clinical Practice Guidelines for Chronic Kidney Disease: Evaluation, Classification, and Stratification. Part 4. Definition and classification of stages of chronic kidney disease. Am J Kidney Dis 2002;39(suppl):S46–S75.
17.
Froissart M, Rossert J, Jacquot C, Paillard M, Houillier P: Predictive performance of the Modification of Diet in Renal Disease and Cockcroft-Gault equations for estimating renal function. J Am Soc Nephrol 2005;16:763–773.
18.
Coresh J, Astor B, McQuillan G, Kusek J, Greene T, Van Lente F, Levey A: Calibration and random variation of the serum creatinine assay as critical elements of using equations to estimate glomerular filtration rate. Am J Kidney Dis 2002;39:920–929.
19.
Stevens LA, Coresh J, Greene T, Levey AS: Assessing kidney function – measured and estimated glomerular filtration rate. N Engl J Med 2006;354:2473–2483.
20.
Keevil BG, Kilpatrick ES, Nichols SP, Maylor PW: Biological variation of cystatin C: Implications for the assessment of glomerular filtration rate. Clin Chem 1998;44:1535–1539.
21.
Finney H, Newman DJ, Gruber W, Merle P, Price CP: Initial evaluation of cystatin C measurement by particle-enhanced immunonephelometry on the Behring nephelometer systems (BNA, BN II). Clin Chem 1997;43:1016–1022.
22.
Stowe H, Lawrence D, Newman DJ, Lamb EJ: Analytical performance of a particle-enhanced nephelometric immunoassay for serum cystatin C using rate analysis. Clin Chem 2001;47:1482–1485.
23.
Knight EL, Verhave JC, Spiegelman D, Hillege HL, de Zeeuw D, Curhan GC, de Jong PE: Factors influencing serum cystatin C levels other than renal function and the impact on renal function measurement. Kidney Int 2004;65:1416–1421.
24.
Grubb A, Nyman U, Bjork J, Lindstrom V, Rippe B, Sterner G, Christensson A: Simple cystatin C-based prediction equations for glomerular filtration rate compared with the Modification of Diet in Renal Disease prediction equation for adults and the Schwartz and the Counahan-Barratt prediction equations for children. Clin Chem 2005;51:1420–1431.
25.
Gaspari F, Perico N, Ruggenenti P, Mosconi L, Amuchastegui CS, Guerini E, Daina E, Remuzzi G: Plasma clearance of nonradioactive iohexol as a measure of glomerular filtration rate. J Am Soc Nephrol 1995;6:257–263.
26.
Brown SC, O’Reilly PH: Iohexol clearance for the determination of glomerular filtration rate in clinical practice: evidence for a new gold standard. J Urol 1991;146:675–679.
27.
Rydstrom M, Tengstrom B, Cederquist I, Ahlmen J: Measurement of glomerular filtration rate by single-injection, single-sample techniques, using 51Cr-EDTA or iohexol. Scand J Urol Nephrol 1995;29:135–139.
28.
Frennby B, Sterner G, Almen T, Hagstam KE, Hultberg B, Jacobsson L: The use of iohexol clearance to determine GFR in patients with severe chronic renal failure – a comparison between different clearance techniques. Clin Nephrol 1995;43:35–46.
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2007
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