Organ crosstalk in kidney diseases: Insights from metabolic, hormonal and nervous regulation.

Kidney diseases, mainly chronic kidney diseases and acute kidney injury, impose a heavy burden on global health care systems. However, traditional kidney-centric therapies, such as dialysis and renal transplantation, face limitations in terms of availability, efficiency and long-term sustainability. Kidney diseases are being increasingly recognized as systemic disorders orchestrated through dynamic interorgan communication. In addition to the kidney itself, multiple organs, such as the gut, liver, and heart, as well as the endocrine and nervous systems, interact to regulate renal function. This cross-talk involves metabolic signals, endocrine mediators, and neural pathways that collectively contribute to the modulation of kidney disease progression. The interactions among these pathways reveal novel therapeutic targets to alleviate kidney injury. However, causal links and organ-specific roles require further mechanistic investigation. This review highlights the need for a multisystem perspective in both the basic research and clinical management of kidney diseases, providing novel insights for the future development of effective, novel therapies targeting extrarenal organs to treat kidney diseases.