Renal-Cardiac Crosstalk in the Pathogenesis and Progression of Heart Failure

Chronic kidney disease (CKD) represents a global health issue with a high socioeconomic impact. Beyond a progressive decline of kidney function, patients with CKD are at increased risk of cardiovascular diseases, including heart failure (HF) and sudden cardiac death. HF in CKD can manifest both as HF with reduced ejection fraction and HF with preserved ejection fraction, with the latter further increasing in relative importance in the more advanced stages of CKD. Typical cardiac remodeling characteristics in uremic cardiomyopathy include left ventricular hypertrophy, myocardial fibrosis, cardiac electrical dysregulation, capillary rarefaction, and microvascular dysfunction, which are triggered by increased cardiac preload, cardiac afterload, and preload and afterload-independent factors. The pathophysiological mechanisms underlying cardiac remodeling in CKD are multifactorial and include neurohormonal activation (with increased activation of the renin-angiotensin-aldosterone system, the sympathetic nervous system, and mineralocorticoid receptor signaling), cardiac steroid activation, mitochondrial dysfunction, inflammation, innate immune activation, and oxidative stress. Furthermore, disturbances in cardiac metabolism and calcium homeostasis, macrovascular and microvascular dysfunction, increased cellular profibrotic responses, the accumulation of uremic retention solutes, and mineral and bone disorders also contribute to cardiovascular disease and HF in CKD. Here, we review the current knowledge of HF in CKD, including the clinical characteristics and pathophysiological mechanisms revealed in animal studies. We also elaborate on the detrimental impact of comorbidities of CKD on HF using hypertension as an example and discuss the clinical characteristics of hypertensive heart disease and the genetic predisposition. Overall, this review aims to increase the understanding of HF in CKD to support future research and clinical translational approaches for improved diagnosis and therapy of this vulnerable patient population.