title: Preclinical Evidence for the Efficacy of Ischemic Postconditioning against Renal Ischemia-Reperfusion Injury, a Systematic Review and Meta-Analysis.
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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: SYstematic Review Centre for Laboratory animal Experimentation (SYRCLE), Radboud university medical center, Nijmegen, The Netherlands.
authors.forename: Simone J
authors.initials: SJ
authors.lastname: Jonker
authors.affiliation: Department of surgery, Radboud university medical center, Nijmegen, The Netherlands.
authors.forename: Theo P
authors.initials: TP
authors.lastname: Menting
authors.affiliation: Department of surgery, Radboud university medical center, Nijmegen, The Netherlands.
authors.forename: Michiel C
authors.initials: MC
authors.lastname: Warlé
authors.affiliation: SYstematic Review Centre for Laboratory animal Experimentation (SYRCLE), Radboud university medical center, Nijmegen, The Netherlands.
authors.forename: Merel
authors.initials: M
authors.lastname: Ritskes-Hoitinga
authors.affiliation: SYstematic Review Centre for Laboratory animal Experimentation (SYRCLE), Radboud university medical center, Nijmegen, The Netherlands.
authors.forename: Kimberley E
authors.initials: KE
authors.lastname: Wever
mesh_terms: D000818:Animals; D005260:Female; D006801:Humans; D019194:Ischemic Preconditioning / Q000379:methods*; D007668:Kidney; D007674:Kidney Diseases / Q000517:prevention & control*; D016030:Kidney Transplantation; D008297:Male; D051381:Rats; D015427:Reperfusion Injury / Q000517:prevention & control*