Association of urine albumin-to-creatinine ratio (UACR) with risks of incident depression and anxiety in adults: A prospective cohort study

Albuminuria, a marker of systemic endothelial dysfunction and renal impairment, has not been fully explored in relation to mental health outcomes. In this study, we investigated the association between albuminuria (assessed by urine albumin-to-creatinine ratio, UACR) and the incidence of depression and anxiety among 369,534 participants from the UK Biobank with available UACR data. Using Cox proportional hazards models and restricted cubic spline analyses, we longitudinally assessed the association between UACR levels and the risk of developing depression and anxiety over a median follow-up of 13.8 years (IQR: 13.1–15.2). During this period, 14,587 incident cases of depression and 15,443 anxiety events were recorded. Compared with participants with UACR <3 mg/mmol, the multivariable-adjusted hazard ratios (HRs) for depression were 1.13 (95% CI 1.06–1.21) for UACR 3–30 mg/mmol and 1.31 (1.02–1.68) for UACR >30 mg/mmol; corresponding HRs for anxiety were 1.13 (1.05–1.20) and 1.81 (1.43–2.29), respectively. These associations remained consistent across multiple sensitivity analyses accounting for potential confounders and were robust in joint models incorporating estimated glomerular filtration rate by the creatinine-cystatin C equation (eGFRcr-cys) or the triglyceride-glucose (TyG) index. Overall, our findings suggest that elevated UACR is associated with an increased risk of developing depression and anxiety, particularly when accompanied by renal impairment or metabolic dysregulation.