Macrophage-mediated injury and repair after ischemic kidney injury

SC Huen, LG Cantley - Pediatric nephrology, 2015 - Springer
SC Huen, LG Cantley
Pediatric nephrology, 2015Springer
Acute ischemic kidney injury is a common complication in hospitalized patients. No
treatment is yet available for augmenting kidney repair or preventing progressive kidney
fibrosis. Animal models of acute kidney injury demonstrate that activation of the innate
immune system plays a major role in the systemic response to ischemia/reperfusion injury.
Macrophage depletion studies suggest that macrophages, key participants in the innate
immune response, augment the initial injury after reperfusion but also promote tubular repair …
Abstract
Acute ischemic kidney injury is a common complication in hospitalized patients. No treatment is yet available for augmenting kidney repair or preventing progressive kidney fibrosis. Animal models of acute kidney injury demonstrate that activation of the innate immune system plays a major role in the systemic response to ischemia/reperfusion injury. Macrophage depletion studies suggest that macrophages, key participants in the innate immune response, augment the initial injury after reperfusion but also promote tubular repair and contribute to long-term kidney fibrosis after ischemic injury. The distinct functional outcomes seen following macrophage depletion at different time points after ischemia/reperfusion injury suggest heterogeneity in macrophage activation states. Identifying the pathways that regulate the transitions of macrophage activation is thus critical for understanding the mechanisms that govern both macrophage-mediated injury and repair in the postischemic kidney. This review examines our understanding of the complex and intricately controlled pathways that determine monocyte recruitment, macrophage activation, and macrophage effector functions after renal ischemia/reperfusion injury. Careful delineation of repair and resolution pathways could provide therapeutic targets for the development of effective treatments to offer patients with acute kidney injury.
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