Which is the RIGHT equation for calculating eGFR? Unfortunately, the answer may be “that depends”. Creatinine and BUN/Urea have long been used as markers of renal function, though creatinine has more recently gained prominence. It was recognized a decade ago that there was significant variation in creatinine assay results from different manufacturers (1). A world-wide effort in the last few years has resulted in the current standardization of almost all creatinine assays being traceable to IDMS, and assay-to-assay recovery differences being significantly reduced if not almost eliminated, though differences in susceptibility to interferences remain (2).
Creatinine measurements still have in vivo variables depending on the patient’s age, gender, race, diet, muscle mass, and a variety of other factors, so relying on broad measures of reference intervals often became misleading. Thus eGFR equations were developed that could account for at least some of these major influences and provide physicians with a more coherent measure of renal function.
Today, the field is in flux with a variety of eGFR reporting choices:
The MDRD Equation: The MDRD equation was originally developed as a measure of eGFR before creatinine assays were standardized. That assay standardization resulted in a 10-25% decrease in many creatinine assays, and a “standardized” MDRD equation was developed that accounted for those assay changes (3). However, a recent study from CAP showed that perhaps 40% of labs were reporting results using newer creatinine assays but still reporting eGFR with the older, non-adjusted MDRD equation (4). Was yours one of them? The MDRD equation has also not been validated for significant groups of patients (the critically ill, extremes of muscle mass or diet, and other conditions), and can give misleading results. Does your lab report eGFR for all creatinine results?
CKD-EPI Equation: The CKD-EPI equation was more recently developed and appears to give a more precise eGFR value across a wider range of results. It is a more complicated set of equations than the MDRD, but may have broader applicability (5, 6).
Cockcroft-Gault Equation and Drug Dosing: Certain drugs have narrow windows of renal tolerance, and dosage levels will vary with renal function. Most of these drugs had their recommended dosages determined by the Cockcroft-Gault equation for eGFR, and this was done before the current era of creatinine assay standardization when recoveries for most assays shifted (7). Can these differences make significant changes in drug dosing and patient responses to therapy?
Schwarz Equation in Pediatrics: Pediatric patients are a special challenge in many areas of laboratory medicine. The Schwartz equation was developed, and recently revised, to estimate GFR in pediatrics (6, 8). Does your lab routinely report GFR in pediatrics?
Cystatin C: Research with Cystatin C has shown it to be a good marker of renal function and prognosis of comorbidities, and is used in distinct equations for eGFR. It has been hampered by wide variabilities in recovery between assays, but the recent availability of a new reference material should help standardize Cystatin C and allow it into more routine use (6, 9). Do you use or expect to use Cystatin C in your lab?
What are your challenges with eGFR reporting? And how do you address them?
- Myers, et al, Clin Chem 2006:52, 5-18.
- Greenberg, et al, Clin Chem 2011:58, 391-401.
- Levey, et al, Clin Chem 2007:53, 766-772.
- National Kidney Disease Education Program, Working Group meeting 2011.
- Levey, et al, Ann Intern Med 2009:150, 604-612.
- National Kidney Disease Education Program: Laboratory Evaluation.
- National Kidney Disease Education Program: CKD and Drug Dosing: Information for Providers.
- Schwartz, et al, J Am Soc Nephrol 2009:20, 629-637.
- Grubb, et al, Clin Chem Lab Med 2010:48, 1619-1621.