Sex-specific impact of chronic kidney disease on mortality and dialysis in heart failure with metabolic syndrome
D Hochstein, R Loutati, V Copeland, S Elimeleh, R Rapahael, K Faierstein, N Abu Amer, M Kunin, A Milwidsky, E Maor, P BeckermanAbstract
Introduction
Cardiovascular-kidney-metabolic (CKM) syndrome is a systemic disorder defined by the overlapping burden of heart failure (HF), chronic kidney disease (CKD), diabetes, and obesity. Although sex differences in cardiovascular disease are increasingly recognized, sex-specific patterns of mortality and renal progression in advanced CKM remain incompletely characterized. We evaluated sex-specific baseline characteristics, mortality, and incident dialysis risk across CKD severity strata
Purpose
To assess sex-specific differences in baseline phenotype, survival, and renal progression across CKD severity strata in patients with CKM.
Methods
Retrospective cohort study using the SHEBAHEART registry (2004 -2025). The study included 5,629 patients with HF and metabolic syndrome. Patients with established CKD (n=2,137; eGFR <60 mL/min/1.73 m²) were stratified by eGFR; 45-59, 30-44, 15-29, and <15 mL/min/1.73 m². Multivariable Cox proportional hazards models were used to assess all-cause mortality. Incident dialysis was evaluated using Fine-Gray competing-risk models Sex-stratified analyses were performed across CKD strata, with formal testing for sex interaction.
Results
Among 5,629 patients (mean age 72.8±11.3 years, 58.2% men), 2,137 had CKD, including 1,195 (55.9%) men and 943 (44.1%) women. Women demonstrated a distinct baseline phenotype, with older age (52.4% vs 34.2% aged ≥80 years) and more frequent elevated pulmonary pressures (SPAP >40 mmHg: 53.4% vs 44.6%), whereas men more often had reduced ejection fraction (LVEF <40%: 34.0% vs 14.2%) and insulin use (35.0% vs 28.7%). Median follow-up was 8.89 years, during which 3,167 patients (56.3%) died. After multivariable adjustment worsening CKD was similarly associated with mortality in men and women (eGFR <60: HR 1.55 vs 1.62; p-interaction=0.875). In contrast, dialysis risk differed by sex. Cause-specific Cox analyses showed earlier incident dialysis in men, and competing-risk analyses confirmed an earlier and steeper rise in dialysis risk in men, becoming significant already in the eGFR 45–59 stratum (adjusted sHR 3.73, 95% CI 2.09–6.63; p<0.001) and increasing to 21.79 in the eGFR <15 stratum. In women, significant dialysis risk emerged only at more advanced CKD (sHR 8.14 at eGFR 15–29; 17.78 at eGFR <15; p<0.001 for all).
Conclusions
In late-stage CKM patients, worsening CKD carries a similar adjusted mortality risk in men and women, but dialysis risk emerges earlier and rises more steeply in men. These findings support closer renal surveillance and earlier management, particularly in men before advanced CKD developsSex Differences - Mortality vs DialysisFine-Gray - Sex-based differences Dialysis