A comparison of GFR estimating formulae based upon s-cystatin C and s-creatinine and a combination of the two

Background. Current recommendations (KDIGO and NKF-KDOQI) are that patients with chronic kidney diseases (CKD) should be classified in stages 1-5 based on GFR. A serum creatinine-based prediction equation (abbreviated MDRD formula) can be used to estimate GFR (eGFR). Cystatin C has been proposed as an alternative filtration marker to creatinine. We present validation of currently used formulae for eGFR based upon s-creatinine and s-cystatin C and we compare two different methods for the determination of cystatin C. Methods. S-cystatin C and s-creatinine were measured in 644 patients referred for determination of GFR by plasma clearance of iohexol during the period 1 June 2004 to 31 December 2005. S-cystatin C was determined by turbidimetry using two different reagents (DAKO AS and Gentian AS). The 644 patients were divided into two groups. Group 1 was used to calculate own eGFR-formulae based on s-cystatin C (Orebro-cyst). Group 2 was used to validate the formulae. Three creatinine-based equations (CockcroftGault, MDRD and Jelliffe) and seven cystatin C-based (Larsson, Hoek, Filler, leBricon, Grubb and Orebro-cyst DAKO, Gentian) were evaluated. Evaluation was done according to the recommendations by KDOQI. Results. In the test sample (group 2) mean GFR (iohexol clearance) was 50.4 ml/min/1.73 m(2) (range 12-150)-mean s-cystatin C (DAKO AS) was 1.63 mg/l and mean s-cystatin C (Gentian AS) 1.92 mg/l. The s-cystatin C concentrations obtained by the Gentian method were approximately 10 lower than the DAKO method within the normal GFR range but were approximately 40 higher within the low GFR range. Bias for the creatinine-based equations was in the range 0.9 to 5.9 ml/min/1.73 m(2) and for the cystatin C-based equations in range 2.4 to 7.9 ml/min/1.73 m(2). Accuracy within 30 ranged from 68.6 to 80.4 and 54.0 to 82.9, respectively. By combining both, an accuracy within 30 for 87.0 could be reached (MDRDcystatin C by Gentian). Overall the patients were correctly classified for the different stages of CKD in 62.1-64.0 for the creatinine-based equations, 61.5-72.0 for the cystatin C-based equations and 70.2-73.9 for the combination. Conclusion. Estimating GFR using formulae based on s-creatinine or s-cystatin C alone was equally accurate according to the NKF K/DOQI guidelines. A formula that combines both provided a greater accuracy. If Cystatin C, which is clearly more expensive, is used, the choice of the cystatin C determination method and an adjusted prediction equation is essential. Use of the IDMS-traceble MDRD seems to yield the best costbenefit ratio for routine practice.