Metabolomics biomarkers and the risk of overall mortality and ESRD in CKD: Results from the Progredir Cohort

IntroductionStudies on metabolomics and CKD have primarily addressed CKD incidence defined as a decline on eGFR or appearance of albuminuria in the general population, with very few evaluating hard outcomes. In the present study, we investigated the association between metabolites and mortality and ESRD in a CKD cohort.Setting and methodsData on 454 participants of the Progredir Cohort Study, Sao Paulo, Brazil were used. Metabolomics was performed by GC-MS (Agilent MassHunter) and metabolites were identified using Agilent Fiehn GC/MS and NIST libraries. After excluding metabolites present in ResultsMean age was 68±12y, mean eGFR-CKDEPI was 38.4±14.6 ml/min/1.73m2 and 57% were diabetic. After adjustments (GC-MS batch, sex, age, DM and eGFR), 18 metabolites remained significantly associated with the composite outcome. Nine metabolites were independently associated with death: D-malic acid (HR 1.84, 95%CI 1.32–2.56, p = 0.0003), acetohydroxamic acid (HR 1.90, 95%CI 1.30–2.78, p = 0.0008), butanoic acid (HR 1.59, 95%CI 1.17–2.15, p = 0.003), and docosahexaenoic acid (HR 0.58, 95%CI 0.39–0.88, p = 0.009), among the top associations. Lactose (SHR 1.49, 95%CI 1.04–2.12, p = 0.03), 2-O-glycerol-α-D-galactopyranoside (SHR 1.76, 95%CI 1.06–2.92, p = 0.03), and tyrosine (SHR 0.52, 95%CI 0.31–0.88, p = 0.02) were associated to ESRD risk, while D-threitol, mannitol and myo-inositol presented strong borderline associations.ConclusionOur results identify specific metabolites related to hard outcomes in a CKD population. These findings point to the need of further exploration of these metabolites as biomarkers in CKD and the understanding of the underlying biological mechanisms related to the observed associations.