Serum Myo-Inositol, Dimethyl Sulfone, and Valine in Combination with Creatinine Allow Accurate Assessment of Renal Insufficiency—A Proof of Concept

Evaluation of renal dysfunction includes estimation of glomerular filtration rate (eGFR) as the initial step and subsequent laboratory testing. We hypothesized that combined analysis of serum creatinine, myo-inositol, dimethyl sulfone, and valine would allow both assessment of renal dysfunction and precise GFR estimation. Bio-banked sera were analyzed using nuclear magnetic resonance spectroscopy (NMR). The metabolites were combined into a metabolite constellation (GFR(NMR)) using n = 95 training samples and tested in n = 189 independent samples. Tracer-measured GFR (mGFR) served as a reference. GFR(NMR) was compared to eGFR based on serum creatinine (eGFR(Crea) and eGFR(EKFC)), cystatin C (eGFR(Cys-C)), and their combination (eGFR(Crea-Cys-C)) when available. The renal biomarkers provided insights into individual renal and metabolic dysfunction profiles in selected mGFR-matched patients with otherwise homogenous clinical etiology. GFR(NMR) correlated better with mGFR (Pearson correlation coefficient r = 0.84 vs. 0.79 and 0.80). Overall percentages of eGFR values within 30% of mGFR for GFR(NMR) matched or exceeded those for eGFR(Crea) and eGFR(EKFC) (81% vs. 64% and 74%), eGFR(Cys-C) (81% vs. 72%), and eGFR(Crea-Cys-C) (81% vs. 81%). GFR(NMR) was independent of patients’ age and sex. The metabolite-based NMR approach combined metabolic characterization of renal dysfunction with precise GFR estimation in pediatric and adult patients in a single analytical step.