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Mechanisms of Disease: cell death in acute renal failure and emerging evidence for a protective role of erythropoietin

Nature Clinical Practice Nephrology volume 1, pages 87–97 (2005)Cite this article

Abstract

Acute renal failure—characterized by a sudden loss of the ability of the kidneys to excrete nitrogenous waste, and to maintain electrolyte homeostasis and fluid balance—is a frequently encountered clinical problem, particularly in the intensive care unit. Unfortunately, advances in supportive interventions have done little to reduce the high mortality associated with this condition. Might erythropoietin (EPO) have utility as a therapeutic agent in acute renal failure? This hormone mediates anti-apoptotic effects in the bone marrow, facilitating maturation and differentiation of erythroid progenitors. New evidence indicates that EPO also exerts anti-apoptotic effects in the brain, heart and vasculature, which can limit the degree of organ damage. Here, we review the emerging biological role of EPO in the kidney and the pathophysiology of ischemia–reperfusion injury in an attempt to understand the therapeutic potential of EPO in acute renal failure.

Key Points

  • Erythropoietin (EPO) is produced in the kidney in response to hypoxia, and exerts anti-apoptotic effects in bone marrow, brain, heart and vasculature

  • Data from animal models indicate that EPO can protect the kidney when administered either before or after onset of an ischemic insult

  • Beneficial effects of EPO in human acute renal failure trials have not yet been detected

  • New EPO derivatives (e.g. carbamylated EPO and desialylated EPO) are more likely to be clinically applicable

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Figure 1: Potential mechanism of anti-apoptotic effects of erythropoietin.
Figure 2: Pathophysiology of cell death in ischemic acute renal failure.

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Acknowledgements

EJ Sharples is supported by a training fellowship from the National Kidney Research Fund (TF17/2004). C Thiemermann is supported in part by the William Harvey Research Foundation.

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  1. William Harvey Research Institute,

    Edward J Sharples, Christoph Thiemermann & Magdi M Yaqoob

  2. Royal London Hospital, London, UK

    Edward J Sharples, Christoph Thiemermann & Magdi M Yaqoob

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Correspondence to Edward J Sharples.

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MM Yaqoob has received research support from Amgen and Roche.

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Sharples, E., Thiemermann, C. & Yaqoob, M. Mechanisms of Disease: cell death in acute renal failure and emerging evidence for a protective role of erythropoietin. Nat Rev Nephrol 1, 87–97 (2005). https://doi.org/10.1038/ncpneph0042

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