NDT Advance Access originally published online on April 12, 2006
Nephrology Dialysis Transplantation 2006 21(6):1733-1734; doi:10.1093/ndt/gfl181
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Reply
Email: rachel_middleton{at}talk21.comSir,
We would like to thank Rigalleau et al. for their comments and interest in our study [1]. They have compared the four-variable MDRD-GFR with isotope-GFR (51Cr-EDTA) in 81 subjects with diabetes and normal mildly impaired renal function and found that the MDRD formula underestimated GFR. This has previously been noted in patients with normal/mildly impaired renal function [2], but they found the difference to be greater in the 30 female subjects studied. The authors do not comment on the method of creatinine analysis or on whether this was calibrated to the Cleveland laboratory where the MDRD formula was first derived from creatinine measures, and so it is difficult to confirm whether there is a true gender bias in the MDRD formula.
Whilst the authors find a significant underestimation of GFR using the MDRD formula compared with isotope GFR measurements, we do not believe this necessarily supports the conclusion that ‘underestimation of high GFR makes it an inappropriate tool for screening diabetic subjects for nephropathy’. An essential requirement of a screening tool is that it is cheap and widely available. Hence, it is inappropriate to compare MDRD-GFR with isotope-GFR, which is both expensive and inappropriate for routine use, and which in addition exposes patients to a significant radiation risk.
We do agree with Rigalleau et al.'s conclusion, that ‘the MDRD equation should be used with caution in patients with normal renal function’. The main limitation of the MDRD formula in routine practice is the well-documented imprecision of the formula at normal renal function. In addition, even in subjects with impaired renal function, difficulties in accurate interpretation exist due to issues regarding calibration of creatinine assays. For example, serum creatinine levels were 20.3 µmol/l higher in the White Sands laboratory for the National Health and Nutrition Examination Survey (NHANES) III study when compared with the Cleveland laboratory which undertook the MDRD study [3]. Methodological problems with serum creatinine assays have their greatest impact within or close to the reference range for creatinine, with wide confidence intervals for an individual GFR, and this should be taken into consideration by clinicians when interpreting results.
In the future, superior markers of renal function in the normal or mildly impaired range, such as cystatin C, may supersede creatinine and GFR estimations. Calibration of individual laboratory's assays to the Cleveland laboratory will help with issues around accuracy in the short term. In the medium term, it is hoped that serum creatinine assays will be calibrated using an internationally agreed standard. Isotope dilution mass spectrometry (IDMS) may replace conventional assays of serum creatinine in the future and the MDRD formula has recently been re-calibrated to IDMS-traceable serum creatinine values [4]. Until there is widespread adoption of IDMS creatinine analysis, we believe the four-variable MDRD formula represents an improvement compared with serum creatinine alone for detection of chronic kidney disease. As with any first order screening test, there is a trade-off of higher sensitivity for lower specificity. Thus, whilst the MDRD GFR is imperfect, we would prefer to choose a relative over-estimation of low-GFR, rather than risk missing a significant number of patients who do have established CKD, but who would be overlooked when using conventional biochemical parameters.
Conflict of interest statement. None declared.
1 Department of Renal Medicine Hope Hospital Salford, UK2 Chronic Disease Research Group,3 University of Minnesota Minneapolis Minnesota, USA4 Evidence of Public Health Unit School of Epidemiology and Health Services University of Manchester, and5 Department of Diabetes and Endocrinology Hope Hospital Salford, UK
References
- Middleton RJ, Foley RN, Hegarty J et al. The unrecognised prevalence og chronic kidney disease in diabetes. Nephrol Dial Transplant 2006; 21: 88–92
[Abstract/Free Full Text] - Poggio ED et al. Performance of the Modification of Diet in Renal Disease and the Cockroft-Gault equations in the estimation of GFR in health and in chronic kidney disease. J Am Soc Nephrol 2005; 16: 459–466
[Abstract/Free Full Text] - Coresh J, Astor BC, McQuillan G et al. Calibration and random variation of the serum creatinine assay as critical elements of using equations to estimate glomerular filtration rate. Am J Kidney Diseases 2002; 39: 920–929[CrossRef][Web of Science][Medline]
- Levey AS, Coresh J, Greene T et al. Expressing the MDRD study equation for estimating GFR with IDMS traceable (gold standard) serum creatinine values. An Abstract at the American Society of Nephrology Meeting, 2005
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