Reliability of GFR Estimated by Creatinine-Based Formulas in Moderate-to-Severe Proteinuria

Key Points GFR estimations are biased in patients with frank nephrotic syndrome, but the problem is uncharacterized in patients with non-nephrotic proteinuria. We investigated the bias and accuracy of eGFR formulas in patients with mild-to-moderate proteinuria participating in the ramipril in nondiabetic renal failure 1 and 2 trials. The CKD Epidemiology Collaboration 2009 and 2021 and European Kidney Function Consortium equations show no significant bias and sufficient accuracy in moderate-to-severe proteinuria. Background Creatinine-based GFR formulas introduce a substantial bias in GFR estimations in patients with frank nephrotic syndrome. The bias and accuracy of creatinine-based GFR estimates (eGFR) in patients with non-nephrotic proteinuria need better characterization. Methods We used data from the Ramipril in Nondiabetic Renal Failure (ramipril in nondiabetic renal failure [REIN] 1) and REIN 2 trials involving nondiabetic CKD patients with proteinuria to compare eGFRs derived from the CKD Epidemiology Collaboration formulas (with and without race) and the European Kidney Function Consortium equations with iohexol clearance (a gold-standard GFR measure, measured GFR [mGFR]). Bias was defined as the median difference between eGFR and mGFR while accuracy was assessed using P30 and P15 metrics, which represent the percentage of eGFR values within ±30% and ±15% of mGFR, respectively. Results The median bias of the three formulas being compared did not differ, being minimal and in a strict range (0.04–0.05 ml/ml per min per 1.73 m 2 ) in the REIN 1 trial and (−0.04 to 0.03 ml/min per 1.73 m 2 ) in the REIN 2 trial. These findings were confirmed in analyses stratified by age and mGFR. The global accuracy of the three formulas regarding P30 % showed sufficient accuracy (P30 >75%) in the REIN 1 trial and all strata in the REIN 2 trial, but the mGFR stratum was <15 ml/min per 1.73 m 2 . Conclusions The CKD Epidemiology Collaboration (with and without race) and European Kidney Function Consortium equations show no significant bias and sufficient accuracy in patients with proteinuria. These formulas can be safely applied to nondiabetic CKD patients with moderate-to-severe proteinuria. Clinical Trial registry name and registration number: This is a post hoc analysis of two trials, REIN 1 and 2, published about 20 years ago.