NDT Advance Access originally published online on April 9, 2008
Nephrology Dialysis Transplantation 2008 23(7):2427-2428; doi:10.1093/ndt/gfn119
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Do we need another equation to estimate GFR from serum creatinine in renal allograft recipients?
Correspondence and offprint requests to: Andrew Rule, Mayo Clinic, Rochester, MN, USA. E-mail: rule.andrew{at}mayo.eduSir,
We read with interest the study by Pöge et al. evaluating a refit version of the MDRD equation and the Mayo Clinic Quadratic equation to improve estimation of GFR in renal allograft recipients [1]. As pointed out by Poge et al., these two equations were not developed using a standardized assay for serum creatinine. Because the same creatinine assay was used to develop these two equations, it still could be shown that differences in the source population can lead to different equations [2]. However, we recognize that it has been difficult to determine to what extent the Mayo Clinic Quadratic and MDRD equations perform differently due to assay calibration versus the source population. A confirmed conversion factor between a standardized assay (i.e. traceable to isotope dilution mass spectroscopy) and the Mayo Clinic assay used to develop these equations may be helpful. Since the Mayo Clinic assay used an uncompensated rate-Jaffe method, the following calibration correction based on assay differences reported in the literature could be used [3]:
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Recently, indirect calibration was reported using historical College of American Pathologists Survey Data on 45 samples sent to the Mayo Clinic and 253 frozen College of American Pathologists samples in the MDRD study [4]:
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More recently, direct calibration was performed using the Cleveland Clinic Roche Enzymatic assay on frozen samples from 144 patients who also had same-day creatinine levels on the Mayo Clinic assay.
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Applying these calibrations to the upper limit of normal for serum creatinine (97.5th percentile in healthy white men and in healthy white women) [5] highlights the differences in these calibration approaches (see Table 1).
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A more important issue may be whether creatinine assay calibration is even adequate to draw inferences about equation performance between populations. Using standardized assays, there was a 0.04 mg/dl rise in creatinine levels over a 10-year period among young adults without diabetes or hypertension that suggested small residual differences in calibration may still bias comparisons between populations [6]. There also may be calibration differences between measured GFR by an iothalamate urinary clearance compared to a 99mTc-DTPA plasma clearance. To compare renal allograft recipients and native kidney disease patients (the population used to derive the MDRD equation), we would argue that, optimally, both populations need to be sampled using the same creatinine and GFR assays. Using this approach, we did not find a statistically significant difference (2.5%, 95% CI: –3.5–9.0%) in measured GFR between transplant recipients and native kidney disease patients at the same serum creatinine level. We did find less correlation between creatinine and measured GFR in transplant recipients (r2 = 0.671) than native kidney disease patients (r2 = 0.770), suggesting there is less precision with GFR estimates among transplant recipients compared to native kidney disease patients [7]. To improve precision, additional variables in creatinine-based equations are needed to better model the non-GFR variability (muscle mass, dietary protein and tubular secretion) than is accomplished with demographics (age, sex and race) alone. For now, we concur that measured GFR has a role in renal allograft recipients, particularly for monitoring disease progression [8].
Conflict of interest statement. None declared.
Mayo Clinic, Rochester, MN, USA
References
- Poge U, Gerhardt T, Stoffel-Wagner B, et al. Can modifications of the MDRD formula improve the estimation of glomerular filtration rate in renal allograft recipients? Nephrol Dial Transplant (2007) 22:3610–3615.
[Abstract/Free Full Text] - Rule AD, Larson TS, Bergstralh EJ, et al. Using serum creatinine to estimate glomerular filtration rate: accuracy in good health and in chronic kidney disease. Ann Intern Med (2004) 141:929–937.
[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 Dis (2002) 39:920–929.[CrossRef][Web of Science][Medline]
- Stevens LA, Manzi J, Levey AS, et al. Impact of creatinine calibration on performance of GFR estimating equations in a pooled individual patient database. Am J Kidney Dis (2007) 50:21–35.[CrossRef][Web of Science][Medline]
- Rule AD, Rodeheffer RJ, Larson TS, et al. Limitations of estimating glomerular filtration rate from serum creatinine in the general population [see comment]. Mayo Clin Proc (2006) 81:1427–1434.
[Abstract/Free Full Text] - Coresh J, Selvin E, Stevens LA, et al. Prevalence of chronic kidney disease in the United States. Jama (2007) 298:2038–2047.
[Abstract/Free Full Text] - Rule AD, Bergstralh EJ, Slezak JM, et al. Glomerular filtration rate estimated by cystatin C among different clinical presentations. Kidney Int (2006) 69:399–405.[CrossRef][Web of Science][Medline]
- Gera M, Slezak JM, Rule AD, et al. Assessment of changes in kidney allograft function using creatinine-based estimates of glomerular filtration rate. Am J Transplant (2007) 7:880–887.[CrossRef][Web of Science][Medline]
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