Increased urinary osmolyte excretion indicates chronic kidney disease severity and progression rate

• Published in: Nephrology, dialysis, transplantation dialysis, transplantation, 2018-12, Vol.33 (12), p.2156-2164
• Main Authors: Gil, Ryan B, Ortiz, Alberto, Sanchez-Niño, Maria D, Markoska, Katerina, Schepers, Eva, Vanholder, Raymond, Glorieux, Griet, Schmitt-Kopplin, Philippe, Heinzmann, Silke S
• Format: Article
• Language: English
• ISSN: 0931-0509; 1460-2385
• DOI: 10.1093/ndt/gfy020

Chronic kidney disease (CKD) is a recognized global health problem. While some CKD patients remain stable after initial diagnosis, others can rapidly progress towards end-stage renal disease (ESRD). This makes biomarkers capable of detecting progressive forms of CKD extremely valuable, especially in non-invasive biofluids such as urine. Screening for metabolite markers using non-targeted metabolomic techniques like nuclear magnetic resonance spectroscopy is increasingly applied to CKD research. A cohort of CKD patients (n = 227) with estimated glomerular filtration rates (eGFRs) ranging from 9.4-130 mL/min/1.73 m2 was evaluated and urine metabolite profiles were characterized in relation to declining eGFR. Nested in this cohort, a retrospective subset (n = 57) was investigated for prognostic metabolite markers of CKD progression, independent of baseline eGFR. A transcriptomic analysis of murine models of renal failure was performed to validate selected metabolomic findings. General linear modeling revealed 11 urinary metabolites with significant associations to reduced eGFR. Linear modelling specifically showed that increased urine concentrations of betaine (P