External Validation of a Novel Multimarker GFR Estimating Equation

Background Using multiple markers may improve accuracy in GFR estimation. We sought to externally validate and compare the performance of a novel multimarker eGFR (panel eGFR) equation among Black and White persons using the Genetic Epidemiology Network of Arteriopathy cohort. Methods We included 224 sex, race/ethnicity, and measured GFR (mGFR) category–matched persons, with GFR measured using urinary clearance of iothalamate. We calculated panel eGFR using serum creatinine, valine, myo-inositol, cystatin C, age, and sex. We compared its reliability with current eGFR equations (2021 CKD Epidemiology Collaboration creatinine [eGFR-Cr] and creatinine with cystatin C [eGFR-Cr-CysC]) using median bias, precision, and accuracy metrics. We evaluated each equation’s performance in age, sex, and race subgroups. Results In the overall cohort, 49% were Black individuals, and mean mGFR was 79 ml/min per 1.73 m². Panel eGFR overestimated mGFR (bias: 22.4 ml/min per 1.73 m²; 95% confidence interval [CI], 24.4 to 20.7), eGFR-Cr-CysC underestimated mGFR (bias: 4.8 ml/min per 1.73 m²; 95% CI, 2.1 to 6.7), while eGFR-Cr was unbiased (bias: 2.0 ml/min per 1.73 m²; 95% CI, 21.1 to 4.6). All equations had comparable accuracy. Among Black male individuals younger than 65 years, both eGFR-Cr (bias: 17.0 ml/min per 1.73 m²; 95% CI, 8.6 to 23.5) and eGFR-Cr-CysC (bias: 14.5 ml/min per 1.73 m²; 95% CI, 6.0 to 19.7) underestimated mGFR, whereas panel eGFR was unbiased (bias: 1.7 ml/min per 1.73 m²; 95% CI, 23.4 to 10.0). Metrics of accuracy for all eGFRs were acceptable in all subgroups except for panel eGFR in Black female individuals younger than 65 years (P30: 73.3%). Conclusions Panel eGFR can be used to estimate mGFR and may have utility among Black male individuals younger than 65 years where current CKD Epidemiology Collaboration equations are biased.