External Validation of a Novel Multimarker GFR Estimating Equation

Abstract

Key Points:

1. Using multiple markers may improve GFR estimation especially in settings where creatinine and cystatin C are known to be limited.

2. Panel eGFR is a novel multimarker eGFR equation consisting of age, sex, cystatin C, and nuclear magnetic resonance–measured creatinine, valine, and myo-inositol.

3. eGFR-Cr and eGFR-Cr-CysC may underestimate measured GFR, while panel eGFR was unbiased among younger Black male individuals.

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: −2.4 ml/min per 1.73 m²; 95% confidence interval [CI], −4.4 to −0.7), 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, −1.1 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, −3.4 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.