A modest proposal for improving the accuracy of creatinine-based GFR-estimating equations

Abstract

The most widely used creatinine-based glomerular filtration rate (GFR) estimating (e) equation (eGFR) is MDRD-4. It and its successor, CKD-EPI, do not include a term for the patient’s body weight or actual body surface area (BSA). There is new and compelling evidence that, as a result, these eGFR equations are vulnerable to bias (non-random errors) that can confound their application to individuals and to group comparisons. Our ‘modest proposal’ is to retrofit these eGFR equations to include the patient’s actual body weight (or a related term—as discussed later) and actual BSA. This editorial documents the problem incurred by these omissions, how the problem can be remedied and what should be done until it is remedied. When MDRD-4 was devised, it was an advantage to not require body weight or BSA because clinical laboratories, which produced the creatinine measurement, did not have ready access to the patient’s height or weight. They did, however, have the patient’s demographics (age, race, sex), each of which influences the serum creatinine level. These demographics and the serum creatinine level became the data set for MDRD-4/CKD-EPI. Now, however, with the widespread and growing use of the electronic medical record, it would be easy to incorporate the patient’s body weight and actual BSA into MDRD-4/CKD-EPI. The MDRD-4 equation was devised to estimate actual GFR more accurately than is possible from interpretation of the serum creatinine level alone [1]. The MDRD-4 equation has become very influential. It is the basis for the K-DOQI stages of chronic kidney disease (CKD) [1], which are widely used clinically and in CKD epidemiology. Also, most clinical laboratories now automatically report MDRD-4 using a standardized creatinine measurement championed by K-DOQI. MDRD-4’s predecessor was Cockroft-Gault (CG) eGFR. CG is used widely in Europe but it never gained popularity in the USA. The disadvantages of CG are that it requires body weight, does not adjust for BSA or African ancestry and estimates creatinine clearance not GFR. Also, CG shows greater variability than MDRD-4, which has been interpreted as evidence of decreased accuracy [1]. We suggest, however, that MDRD-4 only seems more accurate than CG because, in effect, MDRD-4 has only a single variable contributing to its variance (i.e. serum creatinine), whereas CG eGFR has both serum creatinine and body weight contributing to its variance. Thus, for patients of the same age, race, sex and serum creatinine level, there is only one possible value for MDRD-4 eGFR. However, for this same set of patients, there are numerous possible correct values for their CG eGFR, depending on the individuals’ body weight, as we and others have pointed out [2, 3]. The greater variability of CG compared to MDRD-4 reflects this reality. On this basis, we suggest that it is beyond question that adding a weight term and the patient’s actual BSA would improve the accuracy of MDRD-4/CKD-EPI. Presently, there is a considerable effort underway to replace creatinine-based eGFR with other measures [4]. We suggest, however, that a properly retrofitted CKD-EPI may make that effort unnecessary. Body weight is the main determinant of serum creatinine at any actual GFR. MDRD-4 attempts to adjust for lack of a body weight term by using an averaged BSA. However, BSA—even an accurately determined BSA—is not an adequate substitute for body weight. For example, a 35% difference in body weight corresponds to only a 14% difference in BSA [5]. The evidence that MDRD-4 (and by inference CKD-EPI) is biased because it does not include a body weight term or actual BSA, includes the following