Urinary metabolites associated with the long-term risk for chronic kidney disease incidence and progression in hypertensive patients.

Background: Hypertension is a leading risk factor for chronic kidney disease (CKD), yet the metabolic mechanisms linking hypertension to CKD remain unclear. This study aimed to identify metabolites associated with CKD incidence and progression in hypertensive patients using untargeted metabolomics analysis.

Methods: A prospective cohort study was conducted to identify metabolites associated with the incidence and progression of CKD in hypertensive patients. Untargeted metabolomic profiling was conducted, and three statistical models-logistic regression, lasso regression, and random forest-were utilized to identify metabolites associated with CKD. Modified Poisson regression was used to assess the associations between metabolites and kidney-related outcomes.

Results: Untargeted metabolomic profiling identified distinct metabolite patterns distinguishing hypertensive patients with CKD from those without. These metabolites were identified across the three statistical models, with 94 showing significance in at least two. Four metabolites-L-theanine, cysteine-s-sulfate, mesaconic acid, and 2-aminoadipic acid-were inversely associated with CKD incidence and progression. L-theanine and cysteine-s-sulfate were both associated with decreased estimated glomerular filtration rate (eGFR) and increased urinary albumin-to-creatinine ratio (UACR). In contrast, mesaconic acid was linked to increased UACR, and 2-aminoadipic acid was associated with decreased eGFR. Patients at higher risk of CKD progression exhibited significantly lower levels of these metabolites.

Conclusion: L-theanine, cysteine-s-sulfate, mesaconic acid, and 2-aminoadipic acid show an inverse association with CKD incidence and progression in hypertensive patients, suggesting their potential as biomarkers for CKD risk. Further studies are warranted to validate these findings and investigate their therapeutic implications.