GFR Methods Compared | mGFR Versus CrCl | mGFR Versus eGFR |

Commonly used x axis | mGFR | mGFR or (mGFR+eGFR)/2 |

Commonly used y axis | CrCl-to-mGFR ratio | eGFR−mGFR |

Commonly used assessment of bias | Mean of CrCl-to-mGFR ratio | Median or mean of eGFR−mGFR |

Methodologic limitations with the common approach | CrCl 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 ratio | Least 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 error | eGFR; 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 relevance | Tubular 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 biology | The 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.