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Preconditioning against renal ischaemia reperfusion injury: the failure to translate to the clinic

  • Dermot O’Kane
  • Graham S. Baldwin
  • Damien M. Bolton
  • Joseph J. Ischia
  • Oneel Patel
Review
  • 20 Downloads

Abstract

Acute kidney injury (AKI) as a result of ischaemia–reperfusion represents a major healthcare burden worldwide. Mortality rates from AKI in hospitalized patients are extremely high and have changed little despite decades of research and medical advances. In 1986, Murry et al. demonstrated for the first time the phenomenon of ischaemic preconditioning to protect against ischaemia–reperfusion injury (IRI). This seminal finding paved the way for a broad body of research, which attempted to understand and ultimately harness this phenomenon for human application. The ability of preconditioning to limit renal IRI has now been demonstrated in multiple different animal models. However, more than 30 years later, a safe and consistent method of protecting human organs, including the kidneys, against IRI is still not available. This review highlights agents which, despite strong preclinical data, have recently failed to reduce AKI in human trials. The multiple reasons which may have contributed to the failure to translate some of the promising findings to clinical therapies are discussed. Agents which hold promise in the clinic because of their recent efficacy in preclinical large animal models are also reviewed.

Keywords

Ischaemia Reperfusion Preconditioning Zinc Animal models Translation 

Abbreviations

IRI

Ischaemia-reperfusion injury;

HIF

Hypoxia inducible factor

IC

Intermittent clamping

AKI

Acute kidney injury

Notes

Author contributions

Manuscript writing/editing: all authors.

Funding

This work was in part supported by the Austin Health Medical Research Foundation and by The University of Melbourne.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical statement

This article does not contain any studies with human participants or animals performed by any of the authors.

Informed consent

For this type of study formal consent is not required.

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Copyright information

© Italian Society of Nephrology 2019

Authors and Affiliations

  • Dermot O’Kane
    • 1
    • 2
  • Graham S. Baldwin
    • 1
  • Damien M. Bolton
    • 1
    • 2
  • Joseph J. Ischia
    • 1
    • 2
  • Oneel Patel
    • 1
  1. 1.Department of SurgeryAustin Health, The University of MelbourneHeidelbergAustralia
  2. 2.Department of UrologyAustin HealthHeidelbergAustralia

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