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Title: Preconditioning against renal ischaemia reperfusion injury: the failure to translate to the clinic.
Austin Authors: O'Kane, Dermot B ;Baldwin, Graham S;Bolton, Damien M ;Ischia, Joseph J ;Patel, Oneel
Affiliation: Department of Urology, Austin Health, Heidelberg, Victoria, Australia
Department of Surgery, Austin Health, The University of Melbourne, Heidelberg, Victoria, Australia
Issue Date: 11-Aug-2019
Date: 2019-01-11
Publication information: Journal of Nephrology 2019; 132(4): 539-547
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.
DOI: 10.1007/s40620-019-00582-6
ORCID: 0000-0002-0944-8747
Journal: Journal of Nephrology
PubMed URL: 30635875
Type: Journal Article
Subjects: Animal models
Appears in Collections:Journal articles

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