NDT Advance Access originally published online on April 3, 2008
Nephrology Dialysis Transplantation 2008 23(7):2426-2427; doi:10.1093/ndt/gfn147
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Reply
Correspondence and offprint requests to: E-mail: martin.tidman{at}orebroll.seSir,
We appreciate the comments made by Joanna Urbaniak et al. concerning our article [1] and their evaluation of our cystatin C formula for eGFR (Orebro-cyst). Although the methods we both have used for determining cystatin C (Gentian and Dade-Behring) have been shown to give similar results [2], the Orebro-cyst bias of 6 ml/min/1.73 m2 reported by Urbaniak et al. is probably due to the difference in the methods. This problem will not be solved until an international calibrator for cystatin C becomes available.
eGFR from cystatin C and creatinine are associated with different sources of errors. Therefore, the combination of the two markers should give a better overall estimate, which both our studies indicate. The patient population used for deriving the eGFR formula is critical. The serum creatinine concentration at a particular GFR is different in different populations such as healthy, lean or obese adults, children, CKD, diabetes or transplanted patients. The MDRD formula was derived from CKD patients whereas the Mayo Clinic quadratic equation was from both healthy individuals and patients with CKD. A simple way to choose the right formula is to look at the patient, avoiding creatinine formulae for patients with an abnormal muscle mass and cystatin C formulae when the GFR is low. We do not use cystatin C when GFR is <15 ml/min/1.73 m2 since we have found that the 95% confidence interval of eGFR of about ±(30–40%) increases sharply below GFR values <20 ml/min/1.73 m2. Cystatin C is better than creatinine in detecting a slight decrease in renal function and in detecting rapid deterioration in renal function [3].
The subject material in the study of Urbaniak et al. is small, being composed of healthy volunteers, CKD and transplanted patients and was unevenly distributed. Median GFR was 22 ml/min/1.73 m2, with 43 of the 100 patients in stage 5 (<15 ml/min/1.73 m2), where cystatin C in our opinion should not be used. In stages 1 and 2 each patient represents 9%. The bias of 6 ml/min/1.73 m2 of the Orebro-cyst formula makes a large contribution to the low accuracy in stage 5 compared with the other stages. The distribution of stages in the subject material and the fact that cystatin C is a better marker at higher GFR levels may explain that Urbaniak et al. found less bias and higher accuracy for the creatinine-based Mayo Clinic quadratic equation than for the Orebro-cyst. The combination of aMDRD and Orebro-cyst showed less bias than the Mayo Clinic quadratic equation.
The advantage of our formula over other cystatin C formulae for estimating GFR is that Cys-pr and CL-nr can easily be calculated from relatively few patients [1,4] and thus the formula can be adapted to the local laboratory conditions, a necessity as an international standard for cystatin C does not exist.
For routine clinical work creatinine-based formulae for eGFR are adequate, simple to handle and appear to yield the best cost-benefit ratio. Cystatin C should be chosen when the patient has an abnormal muscle mass, changing renal function or when small decrease in renal function is important to detect.
Conflict of interest statement. None declared.
1 Department of Medicine 2 Department of Clinical Chemistry University Hospital of Örebro S-701 85 Örebro, Sweden
References
- Tidman M, Sjostrom P, Jones I. A Comparison of GFR estimating formulae based upon s-cystatin C and s-creatinine and a combination of the two. Nephrol Dial Transplant (2008) 23:154–160.
[Abstract/Free Full Text] - Flodin M, Jonsson AS, Hansson LO, et al. Evaluation of Gentian cystatin C reagent on Abbott Ci8200 and calculation of glomerular filtration rate expressed in mL/min/1.73 m(2) from the cystatin C values in mg/L. Scand J Clin Lab Invest (2007) 67:560–567.[CrossRef][Web of Science][Medline]
- Stevens LA, Coresh J, Greene T, et al. Assessing kidney function—measured and estimated glomerular filtration rate. N Engl J Med (2006) 354:2473–2483.
[Free Full Text] - Sjostrom P, Tidman M, Jones I. Determination of the production rate and non-renal clearance of cystatin C and estimation of the glomerular filtration rate from the serum concentration of cystatin C in humans. Scand J Clin Lab Invest (2005) 65:111–124.[Web of Science][Medline]
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