Preconditioning against renal ischaemia reperfusion injury: the failure to translate to the clinic
| Autor: | Damien M Bolton, Dermot O'Kane, Graham S. Baldwin, Joseph Ischia, Oneel Patel |
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| Rok vydání: | 2019 |
| Předmět: |
Nephrology
medicine.medical_specialty Endpoint Determination 030232 urology & nephrology Ischemia Contrast-induced nephropathy Disease 030204 cardiovascular system & hematology Kidney urologic and male genital diseases Translational Research Biomedical 03 medical and health sciences 0302 clinical medicine Internal medicine medicine Animals Humans Mannitol Ischemic Preconditioning Intensive care medicine Chelating Agents urogenital system business.industry Acute kidney injury Reproducibility of Results Free Radical Scavengers Acute Kidney Injury medicine.disease Diuretics Osmotic Acetylcysteine Disease Models Animal medicine.anatomical_structure Reperfusion Injury Ischemic preconditioning Hypoxia-Inducible Factor 1 business Oligopeptides Reperfusion injury |
| Zdroj: | Journal of Nephrology. 32:539-547 |
| ISSN: | 1724-6059 1121-8428 |
| DOI: | 10.1007/s40620-019-00582-6 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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