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

Jochen Ehrich; Laurence Dubourg; Sverker Hansson; Lars Pape; Tobias Steinle; Jana Fruth; Sebastian Höckner; Eric Schiffer

doi:10.3390/diagnostics11020234

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

Diagnostics (Basel). 2021 Feb 3;11(2):234. doi: 10.3390/diagnostics11020234.

Authors

Jochen Ehrich¹, Laurence Dubourg², Sverker Hansson³, Lars Pape⁴, Tobias Steinle⁵, Jana Fruth⁵, Sebastian Höckner⁵, Eric Schiffer⁵

Affiliations

¹ Department of Pediatric Kidney-, Liver- and Metabolic Diseases, Children's Hospital, Hannover Medical School, 30625 Hannover, Germany.
² Service d'Explorations Fonctionnelles Rénaleset Métaboliques, Hôpital Edouard Herriot, 69437 Lyon, France.
³ Department of Pediatrics, Sahlgrenska University Hospital, 413 45 Gothenburg, Sweden.
⁴ Department of Pediatrics II, University Hospital Essen, 45147 Essen, Germany.
⁵ Department of Research and Development, numaresAG, 93053 Regensburg, Germany.

Abstract

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.

Keywords: biomarker; kidney function; metabolomics; nuclear magnetic resonance spectroscopy.