Table 1.

Assessment of bias between different GFR methods across levels of GFR

GFR Methods ComparedmGFR Versus CrClmGFR Versus eGFR
Commonly used x axismGFRmGFR or (mGFR+eGFR)/2
Commonly used y axisCrCl-to-mGFR ratioeGFR−mGFR
Commonly used assessment of biasMean of CrCl-to-mGFR ratioMedian or mean of eGFR−mGFR
Methodologic limitations with the common approachCrCl and mGFR are independent and both affected by measurement error; to some extent, a low mGFR is caused by measure error, and the corresponding CrCl will be higher (regression to the mean), resulting in an increase in the CrCl-to-mGFR ratioLeast squared linear regression is asymmetric, and eGFR was developed to estimate mGFR; thus, eGFR equations were derived to be unbiased across levels of eGFR, not levels of mGFR or (mGFR+eGFR)/2; commonly used eGFR equations were not derived, such that the mean or median of eGFR−mGFR=0; the MDRD Study and CKD-EPI equations were derived, such that the mean of ln eGFR−ln mGFR=0
More correct x axis(mGFR + CrCl)/2; this is the appropriate setting for application of the Bland–Altman approach; if measurement error with mGFR and CrCl is similar, then (mGFR + CrCl)/2 causes error in the x axis to be equally influenced by mGFR error and CrCl erroreGFR; although eGFR has measurement error from the serum markers, this is already incorporated into how the equation estimates mGFR for the equation population
More correct assessment of bias (y axis)No one correct approach (relative or absolute bias both informative)eGFR should always be assessed for bias the same way that eGFR was derived to be unbiased; for the MDRD Study and CKD-EPI equations, this would be the mean of ln eGFR−ln mGFR and can be reported as a relative bias (percentage bias)
Biologic/clinical relevanceTubular secretion of creatinine is thought to increase as GFR declines; however, the CrCl-to-mGFR ratio increasing as mGFR declines is caused by regression to the mean to some extent rather than biologyThe claim that eGFR underestimates at high levels of GFR is not correct, because eGFR equations were derived to be unbiased at all levels of eGFR for the equation population; rather, eGFR can underestimate GFR in populations that are healthier than the equation population; this is particularly a problem with equations that were developed using all patients with CKD (MDRD Study) or mostly patients with CKD (CKD-EPI) applied to healthy individuals with high-normal marker levels (serum creatinine or cystatin C)
  • mGFR, measured GFR; CrCl, creatinine clearance; MDRD, Modification of Diet in Renal Disease; CKD-EPI, Chronic Kidney Disease Epidemiology Collaboration.