Immune-mediated tubule atrophy promotes acute kidney injury to chronic kidney disease transition

Incomplete repair after acute kidney injury can lead to development of chronic kidney disease. To define the mechanism of this response, we compared mice subjected to identical unilateral ischemia-reperfusion kidney injury with either contralateral nephrectomy (where tubule repair predominates) or contralateral kidney intact (where tubule atrophy predominates). By day 14, the kidneys undergoing atrophy had more macrophages with higher expression of chemokines, correlating with a second wave of proinflammatory neutrophil and T cell recruitment accompanied by increased expression of tubular injury genes and a decreased proportion of differentiated tubules. Depletion of neutrophils and T cells after day 5 reduced tubular cell loss and associated kidney atrophy. In kidney biopsies from patients with acute kidney injury, T cell and neutrophil numbers negatively correlated with recovery of estimated glomerular filtration rate. Together, our findings demonstrate that macrophage persistence after injury promotes a T cell- and neutrophil-mediated proinflammatory milieu and progressive tubule damage. Acute kidney injury can lead to chronic kidney disease. Here the authors show that the transition is related to a macrophage-mediated second wave of inflammatory cells that promote late tubule injury, dedifferentiation and fibrosis. Suppressing this second wave reduced tubular loss and kidney atrophy.

Automated summary

Incomplete repair after acute kidney injury can lead to the development of chronic kidney disease, and this response is mediated by macrophages promoting a proinflammatory environment and progressive tubule injury.