Sex and Cardiovascular Outcomes with Chronic Kidney Disease

Women with chronic kidney disease (CKD) have a high burden of cardiovascular disease (CVD), yet cardiovascular phenotypes and outcomes differ from men because of both biologic factors and care processes. Heart failure is common in CKD; women more often present with heart failure with preserved ejection fraction (HFpEF) and concentric remodeling driven by hypertension, arterial stiffness, inflammation, and microvascular dysfunction, whereas men more commonly demonstrate ischemic substrates and systolic dysfunction, heart failure with reduced ejection fraction (HFrEF). Women tend to have fewer obstructive coronary events but more ischemic symptoms without epicardial obstruction, consistent with microvascular dysfunction compounded by CKD-related endothelial impairment. Although women generally show lower pre-dialysis CVD mortality than men, relative risk rises sharply with declining estimated glomerular filtration rate (eGFR) and albuminuria and the female survival advantage narrows on dialysis, where women may have more heart failure and stroke hospitalizations despite slightly lower cardiovascular mortality. Female-specific exposures including hypertensive disorders of pregnancy and the reproductive transition such as menarche, menstrual cycles, and menopause further shape lifelong cardio-kidney risk trajectories. Despite proven benefits of blood pressure control, statins, renin-angiotensin-aldosterone system blockade, mineralocorticoid antagonists, and sodium-glucose cotransporter 2 (SGLT2) inhibitors with emerging roles for incretin-based therapies, women remain undertreated and underrepresented in CKD and cardio-renal trials. Priorities include consistent sex-disaggregated reporting, improved heart failure phenotyping in CKD, mechanistic study of vascular dysfunction across CKD progression, and implementation strategies to close sex gaps in evidence-based cardio-renal care. This narrative review summarizes sex-based differences across CKD stages and kidney failure in CVD, vascular dysfunction, and therapeutic evidence gaps.