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Macrophage-mediated injury and repair after ischemic kidney injury

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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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Acknowledgements

We acknowledge funding from the National Institutes of Health (DK93771) to L. G. Cantley. S. C. Huen was supported by the National Institute of Diabetes and Digestive and Kidney Diseases Institutional Training Grant (T32-DK007276) and by the American Heart Association (13FTF17070000).

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  1. Department of Medicine, Section of Nephrology, Yale University, PO Box 208029, New Haven, CT, USA

    Sarah C. Huen & Lloyd G. Cantley

  2. Yale University School of Medicine, PO Box 208029, New Haven, CT, 06520, USA

    Sarah C. Huen

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  1. Sarah C. Huen
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Correspondence to Sarah C. Huen.

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Huen, S.C., Cantley, L.G. Macrophage-mediated injury and repair after ischemic kidney injury. Pediatr Nephrol 30, 199–209 (2015). https://doi.org/10.1007/s00467-013-2726-y

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