Title : Cardiorenal syndrome: pathophysiological crosstalk between heart and kidney
Abstract:
Cardiorenal syndrome (CRS) describes the bidirectional deterioration of cardiac and renal func tion, in which dysfunction of one organ induces or perpetuates dysfunction of the other. Since Robert Bright's 1836 observations and the formal five-subtype classification proposed by Ronco and colleagues in 2008, understanding of CRS has evolved from organ-sequential taxonomy to ward a mechanism-driven, phenotype-based framework. This narrative review synthesizes con temporary evidence across the molecular, diagnostic, and therapeutic dimensions of CRS. We examine the convergent pathophysiological pathways underlying the syndrome — hemody namic derangement, renin-angiotensin-aldosterone and sympathetic nervous system activation, systemic inflammation, oxidative stress, mitochondrial and endothelial dysfunction, and the re cently characterized gut-heart-kidney axis — with particular emphasis on venous congestion as a unifying mechanistic driver. We review the global epidemiological burden of cardiorenal over lap, now estimated to affect over half of hospitalized heart failure patients, and appraise the di agnostic evolution from creatinine-dependent assessment toward multi-marker biomarker pan els and point-of-care venous congestion ultrasonography (VExUS). On the therapeutic front, we highlight the shift toward combination pharmacotherapy — particularly finerenone-SGLT2 in hibitor co-administration — alongside device-based decongestive strategies and early applica tions of artificial intelligence in cardiorenal phenotyping. We argue that the traditional five subtype classification, while pedagogically useful, insufficiently captures the overlapping, tran sitional phenotypes seen in clinical practice, and that congestion-quantified, mechanism-specific management increasingly supersedes rigid subtype-based decision-making. This review con cludes by identifying priority areas for future investigation, including randomized congestion guided decongestion trials and prospective validation of artificial intelligence-derived cardiore nal phenotypes, positioning CRS within the broader emerging construct of cardiovascular kidney-metabolic syndrome
