Brain‐Kidney Axis Dysfunction in Intracerebral Hemorrhage: Mechanisms and Interventions

Abstract

Intracerebral hemorrhage (ICH), the most fatal stroke subtype, causes severe acute brain injury and frequent multiple‐organ dysfunction, with renal impairment representing a common and severe complication. ICH patients are susceptible to secondary acute kidney injury (AKI), and many of those who progress to chronic kidney disease (CKD) or even end‐stage renal disease. Although these adverse clinical outcomes are closely associated with the bidirectional brain‐kidney axis, the precise molecular and pathological mechanisms underlying ICH‐related AKI and subsequent CKD progression remain poorly elucidated. The AKI and CKD after ICH are mediated by multiple interconnected pathological mechanisms governed by the dysregulated brain‐kidney axis, including sympathetic nervous system (SNS) overactivation, excessive stimulation of hypothalamic–pituitary–adrenal (HPA) axis and the renin‐angiotensin‐aldosterone system (RAAS), systemic inflammation, oxidative stress injury, and uremic toxin accumulation. These mediators fuel a bidirectional pathogenic cycle between the brain and kidney, while shared microvascular vulnerability as well as hemodynamic characteristics of both organs facilitate such inter‐organ crosstalk. Brain‐kidney axis dysfunction represents the core pathogenesis underlying ICH‐induced secondary renal impairment. Clinical interventions should adopt a brain‐kidney co‐protection strategy, combining neuroprotective, renoprotection, and targeted pathway‐based therapies.