Cardiac and Renal Fibrosis, the Silent Killer in the Cardiovascular Continuum: An Up-to-Date

Abstract

Cardiovascular disease (CVD) and chronic kidney disease (CKD) often coexist and have a major impact on patient prognosis. Organ fibrosis plays a significant role in the pathogenesis of cardio-renal syndrome (CRS), explaining the high incidence of heart failure and sudden cardiac death in these patients. Various mediators and mechanisms have been proposed as contributors to the alteration of fibroblasts and collagen turnover, varying from hemodynamic changes to the activation of the renin–angiotensin system, involvement of FGF 23, and Klotho protein or collagen deposition. A better understanding of all the mechanisms involved has prompted the search for alternative therapeutic targets, such as novel inhibitors of the renin–angiotensin–aldosterone system (RAAS), serelaxin, and neutralizing interleukin-11 (IL-11) antibodies. This review focuses on the molecular mechanisms of cardiac and renal fibrosis in the CKD and heart failure (HF) population and highlights the therapeutic alternatives designed to target the responsible pathways.

Pathophysiological Link and Treatment Implication of Heart Failure and Preserved Ejection Fraction in Patients with Chronic Kidney Disease

“…Fibroblast Growth Factor-23 (FGF-23) is increased in patients with CKD, and it has been shown to alter renal flow-mediated vascular regulation and arterial stiffness. An in vitro study on human atrial myocardiocytes demonstrated a cardiac profibrotic role and induction of myocardial hypertrophy [34]. Deficiency of Klotho protein-positive myocardial regions, the co-receptor of FGFR1, demonstrated in myocardial autoptic samples of dialysis patients with high FGF-23 serum levels, has been associated with higher cardiac fibrosis and ventricular hypertrophy with an inversely proportional relation [35].…”