Estimating Glomerular Filtration Rate from Serum Myo-Inositol, Valine, Creatinine and Cystatin C

Assessment of renal function relies on the estimation of the glomerular filtration rate (eGFR). Existing eGFR equations, usually based on serum levels of creatinine and/or cystatin C, are not uniformly accurate across patient populations. In the present study, we expanded a recent proof-of-concept approach to optimize an eGFR equation targeting the adult population with and without chronic kidney disease (CKD), based on a nuclear magnetic resonance spectroscopy (NMR) derived 'metabolite constellation' (GFR(NMR)). A total of 1855 serum samples were partitioned into development, internal validation and external validation datasets. The new GFR(NMR) equation used serum myo-inositol, valine, creatinine and cystatin C plus age and sex. GFR(NMR) had a lower bias to tracer measured GFR (mGFR) than existing eGFR equations, with a median bias (95% confidence interval [CI]) of 0.0 (-1.0; 1.0) mL/min/1.73 m(2) for GFR(NMR) vs. -6.0 (-7.0; -5.0) mL/min/1.73 m(2) for the Chronic Kidney Disease Epidemiology Collaboration equation that combines creatinine and cystatin C (CKD-EPI2012) (p < 0.0001). Accuracy (95% CI) within 15% of mGFR (1-P15) was 38.8% (34.3; 42.5) for GFR(NMR) vs. 47.3% (43.2; 51.5) for CKD-EPI2012 (p < 0.010). Thus, GFR(NMR) holds promise as an alternative way to assess eGFR with superior accuracy in adult patients with and without CKD.

Automated summary

The study optimized an eGFR equation targeting the adult population using a nuclear magnetic resonance spectroscopy (NMR) derived 'metabolite constellation' (GFR(NMR)), which showed lower bias and higher accuracy compared to existing eGFR equations. The new GFR(NMR) equation included serum myo-inositol, valine, creatinine, cystatin C, age and sex, providing superior accuracy in assessing eGFR in adult patients with and without chronic kidney disease (CKD).