Abstract
BACKGROUND: The urine albumin-to-creatinine ratio (UACR) serves as an indicator of renal and cardiovascular risk, but its role within the Cardiovascular-Kidney-Metabolic Syndrome (CKM) and its prognostic value are not fully defined. This study explores the role of the UACR in the context of CKM and its prognostic value for all-cause and cardiovascular disease (CVD) mortality. METHODS: Data from the 1999-2018 National Health and Nutrition Examination Survey was used in this cross-sectional and prospective cohort study, which included 25,353 adults. Multivariate regression analysis was used to evaluate adjusted odds ratios (ORs) and hazard ratios (HRs). Subgroup analysis and interaction tests were carried out to verify the reliability of the results. RESULTS: The multivariate analysis showed that higher UACR was significantly correlated with CKM. Each 100 mg/g rise in UACR as a continuous variable was linked to increased odds for stage 3 (OR: 1.16, 95% CI: 1.14-1.19) and stage 4 (OR: 1.12, 95% CI: 1.10-1.15). Categorically, UACR ≥ 300 mg/g was associated with stage 3 (OR: 15.67, 95% CI: 15.58-15.77) and stage 4 (OR: 6.06, 95% CI: 6.03-6.09). Higher UACR levels were significantly associated with lower survival probabilities. According to fully adjusted Cox models, every 100 mg/g rise in UACR correlated with a 2% higher risk of mortality from all causes (HR: 1.02, 95% CI: 1.02-1.02) and CVD (HR: 1.02, 95% CI: 1.02-1.03). Those with a UACR ≥ 300 mg/g exhibited the highest risks for mortality from all causes (HR: 2.83, 95% CI: 2.52-3.18) and from CVD (HR: 2.94, 95% CI: 2.37-3.66). These associations were consistent across most subgroups. CONCLUSION: In conclusion, higher UACR is independently associated with advanced CKD stages and shows a significant association with increased risks of all-cause and CVD mortality among CKD patients, suggesting that it may be a useful prognostic indicator in CKD syndrome. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40200-026-01892-w.