Chronic Kidney Disease-Associated Cardiomyopathy: Mechanisms and Therapeutic Strategies

Chronic kidney disease-associated cardiomyopathy (CKD-CM) is a term that captures the spectrum of myocardial disease that begins early in chronic kidney disease (CKD) and progresses as kidney function declines. Historically described as uremic cardiomyopathy, the condition was associated with severe left ventricular hypertrophy and fibrosis in patients with kidney failure. However, functional abnormalities and myocardial injury have been shown to begin much earlier, with diffuse interstitial fibrosis preceding overt hypertrophy or reduced ejection fraction. Fibrosis drives heart failure with preserved ejection fraction (HFpEF)-like physiology and atrial fibrillation and increases arrhythmic risk. In this review, we describe the multiple interacting mechanisms, including abnormal loading, neurohormonal activation, metabolic and inflammatory stress, mineral bone disorder, and microvascular dysfunction. We summarize imaging findings across CKD stages and describe established and emerging therapeutic strategies. A better understanding of CKD-CM pathogenesis is likely to enable early intervention and prevention, with successful outcomes measured by reduced progression to severe cardiomyopathy and lower cardiovascular mortality in CKD.