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Preclinical Evidence for the Efficacy of Ischemic Postconditioning against Renal Ischemia-Reperfusion Injury, a Systematic Review and Meta-Analysis

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  • Simone J Jonker
  • Theo P Menting
  • Michiel C Warlé
  • Merel Ritskes-Hoitinga
  • Kimberley E Wever

Abstract

Background: Renal ischemia-reperfusion injury (IRI) is a major cause of kidney damage after e.g. renal surgery and transplantation. Ischemic postconditioning (IPoC) is a promising treatment strategy for renal IRI, but early clinical trials have not yet replicated the promising results found in animal studies. Method: We present a systematic review, quality assessment and meta-analysis of the preclinical evidence for renal IPoC, and identify factors which modify its efficacy. Results: We identified 39 publications studying >250 control animals undergoing renal IRI only and >290 animals undergoing renal IRI and IPoC. Healthy, male rats undergoing warm ischemia were used in the vast majority of studies. Four studies applied remote IPoC, all others used local IPoC. Meta-analysis showed that both local and remote IPoC ameliorated renal damage after IRI for the outcome measures serum creatinine, blood urea nitrogen and renal histology. Subgroup analysis indicated that IPoC efficacy increased with the duration of index ischemia. Measures to reduce bias were insufficiently reported. Conclusion: High efficacy of IPoC is observed in animal models, but factors pertaining to the internal and external validity of these studies may hamper the translation of IPoC to the clinical setting. The external validity of future animal studies should be increased by including females, comorbid animals, and transplantation models, in order to better inform clinical trial design. The severity of renal damage should be taken into account in the design and analysis of future clinical trials.

Suggested Citation

  • Simone J Jonker & Theo P Menting & Michiel C Warlé & Merel Ritskes-Hoitinga & Kimberley E Wever, 2016. "Preclinical Evidence for the Efficacy of Ischemic Postconditioning against Renal Ischemia-Reperfusion Injury, a Systematic Review and Meta-Analysis," PLOS ONE, Public Library of Science, vol. 11(3), pages 1-19, March.
    • Handle: RePEc:plo:pone00:0150863
    DOI: 10.1371/journal.pone.0150863
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    References listed on IDEAS

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    1. Konstantinos K Tsilidis & Orestis A Panagiotou & Emily S Sena & Eleni Aretouli & Evangelos Evangelou & David W Howells & Rustam Al-Shahi Salman & Malcolm R Macleod & John P A Ioannidis, 2013. "Evaluation of Excess Significance Bias in Animal Studies of Neurological Diseases," PLOS Biology, Public Library of Science, vol. 11(7), pages 1-10, July.
    2. Kimberley E Wever & Theo P Menting & Maroeska Rovers & J Adam van der Vliet & Gerard A Rongen & Rosalinde Masereeuw & Merel Ritskes-Hoitinga & Carlijn R Hooijmans & Michiel Warlé, 2012. "Ischemic Preconditioning in the Animal Kidney, a Systematic Review and Meta-Analysis," PLOS ONE, Public Library of Science, vol. 7(2), pages 1-10, February.
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    Cited by:

    1. Nienke A Hesen & Niels P Riksen & Bart Aalders & Merel Ritskes-Hoitinga & Saloua El Messaoudi & Kimberley E Wever, 2017. "A systematic review and meta-analysis of the protective effects of metformin in experimental myocardial infarction," PLOS ONE, Public Library of Science, vol. 12(8), pages 1-18, August.
    2. Kimberley E Wever & Moira H D Bruintjes & Michiel C Warlé & Carlijn R Hooijmans, 2016. "Renal Perfusion and Function during Pneumoperitoneum: A Systematic Review and Meta-Analysis of Animal Studies," PLOS ONE, Public Library of Science, vol. 11(9), pages 1-25, September.

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