Bidirectional kidney–brain crosstalk in AKI, CKD, and acute brain injury: mechanisms, biomarkers, and translational perspectives

The kidney and brain share vascular, metabolic, immune, and neuroendocrine pathways through which dysfunction in either organ can affect the other. Acute kidney injury is associated with delirium and encephalopathy, whereas chronic kidney disease contributes to a longer-term burden of cognitive and cerebrovascular impairment. Retained solutes, drug accumulation, endothelial injury, and systemic inflammation can disrupt the blood-brain barrier and alter glial and neuronal function. Recent experimental studies identify microglial potassium efflux, inflammasome activation, gasdermin D signaling, and ferroptotic stress as components of these responses. Changes in Klotho-FGF23 signaling and impaired perivascular brain clearance provide additional links between renal dysfunction and neurological vulnerability. In the reverse direction, kidney injury after acute brain injury reflects overlapping brain-driven responses, secondary systemic or treatment-related insults, and pre-existing renal and vascular susceptibility. This narrative review brings these mechanisms together with clinical observations and findings from proteomics, metabolomics, and single-cell transcriptomics. It also examines how kidney function affects circulating neurological biomarkers and how study design influences their interpretation. Established management focuses on reversible metabolic disturbances, renal and cerebral perfusion, and medication-related risk. Experimental interventions are discussed according to the disease models and outcomes studied, with emphasis on the evidence needed to translate molecular targets into improvements in cognition, neurological recovery, and kidney function.