Renal recovery after sepsis-associated acute kidney injury: multicellular responses and therapeutic implications

Sepsis is life-threatening organ dysfunction caused by a dysregulated host response to infection, and the kidney is a common site of injury. Sepsis-associated acute kidney injury (SA-AKI) has been reported in approximately half of hospitalised patients with sepsis and is associated with increased mortality and subsequent kidney dysfunction. Yet serum creatinine and urine output reveal little about the processes underlying sustained recovery. This narrative review synthesises experimental and clinical evidence on the timing of kidney injury and repair and on interactions among tubular, vascular, immune, and stromal cells. Experimental studies suggest that reduced tubular activity may be reversible and that repair responses can emerge before kidney function improves. Tubular redifferentiation, metabolic recovery, and microvascular oxygen delivery are interdependent; immune and stromal responses may support repair or perpetuate inflammation and fibrosis. We describe the restoration of these functions as coordinated repair, a framework requiring validation in patients. Pharmacological studies should distinguish acute protection from sustained recovery and evaluate interventions after injury has developed, with survival and kidney outcomes assessed together. Longitudinal human studies are needed to identify immune and tissue responses that predict sustained recovery and may provide therapeutic targets.