Brain-Kidney Axis Dysfunction in Intracerebral Hemorrhage: Mechanisms and Interventions.

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.