Heart Failure With Preserved Ejection Fraction and Chronic Kidney Disease: From Pathophysiology to Treatment

Heart failure with preserved ejection fraction (HFpEF) is an increasingly prevalent subtype of heart failure. It is characterized by a heterogeneous clinical phenotype, a less understood pathophysiology, and multifactorial etiologies. A frequent comorbidity of HFpEF is chronic kidney disease (CKD). The cardiorenal phenotype in HFpEF is growing in prevalence and represents a high-risk clinical population. HFpEF and CKD are interconnected through complex, bidirectional processes involving systemic inflammation, neurohormonal activation, hemodynamic changes, and iron deficiency. These overlapping processes, along with common risk factors, exacerbate disease presentation and progression, contributing to significantly worse outcomes, including higher rates of hospitalization, mortality, and progression to end-stage kidney disease. Historically, treatment options for HFpEF have been limited, but recent studies have identified agents with both cardiovascular and renal benefits. Emerging therapies, such as SGLT2 inhibitors, nonsteroidal MRAs, and GLP-1 receptor agonists, offer a new hope for improving outcomes in the HFpEF cardiorenal population. However, challenges related to diagnosis, volume and potassium management, and barriers such as underdiagnosis and undertreatment still remain. An integrative, multidisciplinary approach is essential for effectively managing patients with both HFpEF and CKD.