AKI as a systemic syndrome and its impact on other organ systems

Acute kidney injury (AKI) affects approximately 15% of all hospitalized individuals and nearly half of those admitted to intensive care units and is increasingly recognized as a systemic syndrome whose consequences extend well beyond structural and functional changes confined to the kidney. Experimental studies highlight the role of inflammation and accumulation of metabolites as pivotal drivers in the cross-talk between the kidneys and distant organ systems during AKI. Whereas clinical data reveals an association between AKI and non-renal organ dysfunctions and complications. This review outlines the pathophysiological mechanisms underlying AKI-associated remote organ dysfunction, focusing on five key organ systems: the lungs, the brain, the heart, the liver and the immune system. We discuss the direct consequences of reduced kidney function alongside the repercussions of the inflammatory cascade triggered by kidney cell injury and the resulting clinical implications. Recognizing that multi-organ failure significantly influences patients' morbidity and mortality, identifying specific pathways of organ cross-talk is essential to optimize clinical management. Finally, we evaluate novel endpoints for future AKI trials. Given that traditional long-term metrics, such as Major Adverse Kidney Events (MAKE), present significant design challenges in non-enriched populations, we analyze alternative and surrogate outcomes, including those directly related to the remote organ complications of AKI.