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Ischemic preconditioning in the animal kidney, a systematic review and meta-analysis.

ABSTRACT: Ischemic preconditioning (IPC) is a potent renoprotective strategy which has not yet been translated successfully into clinical practice, in spite of promising results in animal studies. We performed a unique systematic review and meta-analysis of animal studies to identify factors modifying IPC efficacy in renal ischemia/reperfusion injury (IRI), in order to enhance the design of future (clinical) studies. An electronic literature search for animal studies on IPC in renal IRI yielded fifty-eight studies which met our inclusion criteria. We extracted data for serum creatinine, blood urea nitrogen and histological renal damage, as well as study quality indicators. Meta-analysis showed that IPC reduces serum creatinine (SMD 1.54 [95%CI 1.16, 1.93]), blood urea nitrogen (SMD 1.42 [95% CI 0.97, 1.87]) and histological renal damage (SMD 1.12 [95% CI 0.89, 1.35]) after IRI as compared to controls. Factors influencing IPC efficacy were the window of protection (<24 h = early vs. ? 24 h = late) and animal species (rat vs. mouse). No difference in efficacy between local and remote IPC was observed. In conclusion, our findings show that IPC effectively reduces renal damage after IRI, with higher efficacy in the late window of protection. However, there is a large gap in study data concerning the optimal window of protection, and IPC efficacy may differ per animal species. Moreover, current clinical trials on RIPC may not be optimally designed, and our findings identify a need for further standardization of animal experiments.

SUBMITTER: Wever KE

PROVIDER: S-EPMC3289650 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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Ischemic preconditioning in the animal kidney, a systematic review and meta-analysis.

Wever Kimberley E KE Menting Theo P TP Rovers Maroeska M van der Vliet J Adam JA Rongen Gerard A GA Masereeuw Rosalinde R Ritskes-Hoitinga Merel M Hooijmans Carlijn R CR Warlé Michiel M

PloS one 20120228 2

Ischemic preconditioning (IPC) is a potent renoprotective strategy which has not yet been translated successfully into clinical practice, in spite of promising results in animal studies. We performed a unique systematic review and meta-analysis of animal studies to identify factors modifying IPC efficacy in renal ischemia/reperfusion injury (IRI), in order to enhance the design of future (clinical) studies. An electronic literature search for animal studies on IPC in renal IRI yielded fifty-eigh ...[more]

PMID: 22389693

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Project description:Background: As not all ischemic stroke patients benefit from currently available treatments, there is considerable need for neuroprotective co-therapies. Therapeutic hypothermia is one such co-therapy, but numerous issues have hampered its clinical use (e.g., pneumonia risk with whole-body cooling). Some problems may be avoided with brain-specific methods, such as intra-arterial selective cooling infusion (IA-SCI) into the arteries supplying the ischemic tissue. Objective: Our research question was about the efficacy of IA-SCI in animal middle cerebral artery occlusion models. We hypothesized that IA-SCI would be beneficial, but translationally-relevant study elements may be missing (e.g., aged animals). Methods: We completed a systematic review of the PubMed database following the PRISMA guidelines on May 21, 2020 for animal studies that administered IA-SCI in the peri-reperfusion period and assessed infarct volume, behavior (primary meta-analytic endpoints), edema, or blood-brain barrier injury (secondary endpoints). Our search terms included: "focal ischemia" and related terms, "IA-SCI" and related terms, and "animal" and related terms. Nineteen studies met inclusion criteria. We adapted a methodological quality scale from 0 to 12 for experimental design assessment (e.g., use of blinding/randomization, a priori sample size calculations). Results: Studies were relatively homogenous (e.g., all studies used young, healthy animals). Some experimental design elements, such as blinding, were common whereas others, such as sample size calculations, were infrequent (median methodological quality score: 5; range: 2-7). Our analyses revealed that IA-SCI provides benefit on all endpoints (mean normalized infarct volume reduction = 23.67%; 95% CI: 19.21-28.12; mean normalized behavioral improvement = 35.56%; 95% CI: 25.91-45.20; mean standardized edema reduction = 0.95; 95% CI: 0.56-1.34). Unfortunately, blood-brain barrier assessments were uncommon and could not be analyzed. However, there was substantial statistical heterogeneity and relatively few studies. Therefore, exploration of heterogeneity via meta-regression using saline infusion parameters, study quality, and ischemic duration was inconclusive. Conclusion: Despite convincing evidence of benefit in ischemic stroke models, additional studies are required to determine the scope of benefit, especially when considering additional elements (e.g., dosing characteristics). As there is interest in using this treatment alongside current ischemic stroke therapies, more relevant animal studies will be critical to inform patient studies.

Dataset Information

Ischemic preconditioning in the animal kidney, a systematic review and meta-analysis.

Publications

Ischemic preconditioning in the animal kidney, a systematic review and meta-analysis.

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