Urinary stress hormones and their metabolites as predictive biomarkers for CKD with diabetes

Abstract Aims This study aimed to characterize urinary stress hormones and their metabolites in patients with chronic kidney disease associated with diabetes (CKD with diabetes) and to evaluate their associations with renal function, providing insights into stress-related mechanisms and potential biomarker utility. Materials and methods We enrolled 735 participants, including 449 with type 2 diabetes mellitus(T2D)and 286 with CKD with diabetes. Urinary concentrations of norepinephrine, cortisol, aldosterone, and 17-ketosteroids were analyzed. Statistical methods included correlation and regression analyses, receiver operating characteristic (ROC) curves, and orthogonal partial least squares discriminant analysis (OPLS-DA) to evaluate diagnostic value. Results Urinary norepinephrine, cortisol, and 17-ketosteroids levels were significantly lower in CKD patients with diabetes than in those with diabetes alone. Norepinephrine was inversely correlated with albumin-to-creatinine ratio, urinary microalbumin, blood urea nitrogen, and serum creatinine, and positively with estimated glomerular filtration rate. Similar trends were observed for cortisol and 17-ketosteroids. Aldosterone was also negatively correlated with urinary microalbumin and creatinine. OPLS-DA showed distinct metabolic profiles between CKD with diabetes and diabetes, suggesting metabolic heterogeneity. Multivariate logistic regression identified norepinephrine as an independent protective factor, while diastolic blood pressure, urinary glucose, and homovanillic acid were risk factors. A composite model integrating norepinephrine, 17-ketosteroids, and homovanillic acid demonstrated high diagnostic performance, with the norepinephrine-based model achieving an AUC of 0.831 in validation. Conclusion Urinary adrenal hormones and their metabolites provide valuable insights into stress-related mechanisms in CKD with diabetes and may hold potential as complementary noninvasive biomarkers for disease assessment. Clinical trial number Not applicable.