Chronic kidney disease in metabolic syndrome and heart failure: elevated risk, underutilized therapies, and missed opportunities for improved outcomes

Abstract

Cardiovascular-kidney-metabolic (CKM) syndrome is a systemic disorder involving heart disease, kidney disease, diabetes, and obesity. Chronic kidney disease (CKD) is highly prevalent in this advanced phenotype, increases mortality risk, and complicates optimal therapy selection. We evaluated mortality, dialysis risk, and treatment patterns across CKD severity strata in patients with heart failure and metabolic syndrome. To assess the prognostic and therapeutic impact of CKD in heart failure patients with metabolic syndrome. Retrospective analysis of the SHEBAHEART registry (2004-2025). Among 5,629 patients with heart failure and metabolic syndrome, those with CKD were stratified by eGFR 45-59, 30-44, 15-29, and <15 mL/min/1.73 m2, and each group was compared with patients with eGFR ≥60. All-cause mortality was assessed using multivariable Cox models. Dialysis risk was assessed using both Cox and Fine-Gray competing-risk analyses. Among 5,629 patients (mean age 72.8 years, 58.2% male), 2,137 (38.0%) had CKD with 881 (15.7%), 654 (11.6%), 433 (7.7%) and 169 (3.0%) in each respective strata. Median follow-up was 8.89 years, during which 3,167 (56.3%) patients died. Mortality increased stepwise with worsening renal function, with adjusted HRs rising from 1.28 in eGFR 45-59 to 2.14 in eGFR <15; CKD overall was associated with 41% excess mortality risk. Dialysis risk rose dramatically with worsening CKD, with adjusted HRs increasing from 2.58 in eGFR 45-59 to 95.14 in eGFR <15. After accounting for the competing risk of death, CKD remained associated with a profoundly higher likelihood of progression to dialysis, with more than a fivefold excess risk overall. As kidney function declined, use of ACEI/ARBs, MRAs, ARNIs, and SGLT2 inhibitors decreased. In adjusted models, ACEI/ARB therapy remained associated with lower mortality and lower dialysis risk, including after accounting for competing death, whereas the apparent dialysis benefit of SGLT2 inhibitors was attenuated and no longer statistically significant in competing-risk analysis. In patients with late-stage metabolic syndrome, CKD identifies a high-risk subgroup with a graded increase in mortality and dialysis risk compared with eGFR ≥60. The heightened dialysis risk remained pronounced after accounting for competing death. As kidney function worsened, use of foundational therapies declined despite protective signals against mortality and dialysis, highlighting a potentially important missed therapeutic opportunity in advanced cardiorenal disease.CKD Mortality vs DialysisAdjusted Mortality and Dialysis Risk per Drug