Urinary albumin-to-creatinine ratio and all-cause and cause-specific mortality in chronic kidney disease patients with suspected or known coronary artery disease: the EXCEED-J Study

Background The urinary albumin-to-creatinine ratio (UACR) is an important indicator of kidney damage. A meta-analysis indicates that a UACR of 30 mg/g or greater is associated with an increased risk of coronary artery disease (CAD), cardiovascular (CV) mortality, and all-cause mortality in the general population. However, the associations of UACR with all-cause and cause-specific mortality in chronic kidney disease (CKD) patients with suspected or known CAD are unclear. Methods UACR was measured in 1,078 CKD (defined as an estimated glomerular filtration rate [eGFR] of less than 60 mL/min/1.73 m2) patients with suspected or known CAD enrolled in the EXCEED-J study. Patients were divided into 4 categories according to UACR: low (≤10 mg/g), normal-high (10<, ≤30 mg/g), microalbuminuria (30<, ≤300 mg/g), and macroalbuminuria (>300 mg/g). The outcomes were all-cause death, CV death, non-CV death, cancer death, and non-CV-non-cancer death over a 6-year follow-up period. Results During the follow-up, 230 (21.3%) deaths occurred, including 79 (7.3%) CV deaths, 123 (11.4%) non-CV deaths, 47 (4.4%) cancer deaths, and 75 (7.0%) non-CV-non-cancer deaths. Figure 1 shows the Kaplan-Meier curves for all-cause, CV, non-CV, cancer, and non-CV-non-cancer mortality stratified by UACR categories. After adjustment for potential clinical confounders and established CV biomarkers (i.e., N-terminal pro-brain natriuretic peptide, high-sensitivity cardiac troponin I, and high-sensitivity C-reactive protein), both UACR (for 1-category increase) and log-transformed (Ln-) UACR (for 1-SD increase) were significantly associated with all-cause death (hazard ratio [HR], 1.27; 95% confidence interval [CI], 1.10–1.47 and HR, 1.25; 95% CI, 1.07–1.45), non-CV death (HR, 1.40; 95% CI, 1.14–1.72, and HR, 1.40; 95% CI, 1.13–1.73), and non-CV-non-cancer death (HR, 1.68; 95% CI, 1.28–2.21 and HR, 1.69; 95% CI, 1.28–2.23), but not with CV death (HR, 1.18; 95% CI, 0.91–1.53 and HR, 1.16; 95% CI, 0.88–1.51) or cancer death (HR, 1.11; 95% CI, 0.80–1.54 and HR, 1.10; 95% CI, 0.78–1.56) (Fig. 2). The addition of either UACR (for 1-category increase) or log-transformed (Ln-) UACR (for 1-SD increase) to the model with potential clinical confounders and established CV biomarkers further improved the prediction of all-cause death (all P < 0.05 for continuous net reclassification improvement [NRI] and integrated discrimination improvement [IDI]), but not that of non-CV death or non-CV-non-cancer death. Conclusions In CKD patients with suspected or known CAD, higher UACR was independently associated with all-cause and non-CV mortality, specifically non-CV-non-cancer death, but not with CV or cancer death. These findings suggest that UACR acts as a potent indicator of systemic vulnerability rather than a specific CV risk marker in this high-risk population, highlighting its utility in identifying patients at risk for diverse non-cardiovascular fatal events.