Abstract / Summary
Background and Objectives: Long-term renal and cardiovascular outcomes represent major clinical burdens in predialysis chronic kidney disease (CKD). This study aimed to evaluate the long-term incidence of and clinical factors associated with major adverse kidney events (MAKEs) and incident major adverse cardiovascular events (MACEs) in patients with predialysis CKD. Materials and Methods: This retrospective cohort included 263 adults with predialysis CKD followed for at least five years. Patients with baseline dialysis, kidney transplantation, coronary artery disease, heart failure, stroke, or malignancy were excluded. MAKE was defined as chronic dialysis, kidney transplantation, or a ≥50% decline in baseline eGFR. MACE comprised nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. Separate multivariable Cox regression models were constructed for MAKE and MACE, with treatment exposures modeled as time-dependent covariates. Fine–Gray competing-risk regression was performed as a sensitivity analysis. Results: During a median follow-up of 2829 days, MAKE occurred in 97 patients (36.9%) and MACE in 53 (20.2%), corresponding to incidence rates of 47.8 and 26.0 per 1000 person-years, respectively. In multivariable Cox models for MAKE, lower baseline eGFR (HR per 10 mL/min/1.73 m2 increase 0.84, 95% CI 0.72–0.98; p = 0.024) and greater albuminuria severity were independently associated with risk. Compared with normal albuminuria, microalbuminuria and macroalbuminuria were associated with approximately fourfold and eightfold higher hazards, respectively (HR 4.15, 95% CI 1.91–9.00; and HR 7.73, 95% CI 4.01–14.90; both p < 0.001). For MACE, older age (HR per 10 years 1.52, 95% CI 1.12–2.06; p = 0.007) and diabetes mellitus (HR 3.00, 95% CI 1.60–5.62; p < 0.001) were independently associated with higher risk, while higher baseline eGFR was associated with lower risk in the treatment-adjusted models (HR per 10 mL/min/1.73 m2 0.76; p = 0.032–0.037). Neither time-dependent SGLT2 inhibitor nor ACE inhibitor/ARB use was significantly associated with MAKE or MACE. Fine–Gray competing-risk analyses yielded broadly consistent results. SGLT2 inhibitor exposure occurred in 75 patients (28.5%), and treatment-related findings should be interpreted cautiously given the limited exposure and observational design. Conclusions: MAKE and MACE were common in predialysis CKD. Lower baseline kidney function and albuminuria severity were associated with adverse kidney outcomes, whereas older age, diabetes mellitus, and lower baseline kidney function were associated with incident cardiovascular events. These findings highlight distinct renal and cardiovascular risk profiles in predialysis CKD.