The mechanisms underlying acute kidney injury (AKI) progression are incompletely understood, and there are currently no effective treatments available. Arai et al. report a key role of the apoptosis inhibitor of macrophage (AIM) in AKI recovery. During AKI in mice, AIM accumulates on necrotic cell debris within the kidney proximal tubules, interacting with kidney injury molecule 1 (KIM1) expressed on injured tubular epithelial cells to enhance phagocytic removal of debris. Treatment of mice subjected to severe ischaemia–reperfusion-induced AKI with recombinant AIM promoted the clearance of debris and reduced mortality.