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

Jonker, Simone J.; Menting, Theo P; Warlé, Michiel C.; Ritskes‐Hoitinga, Merel; Wever, Kimberley E.

doi:10.1371/journal.pone.0150863

Cited by 24 publications

(15 citation statements)

References 56 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In renal ischemia-reperfusion, ischemic preconditioning [ 14 ] and postconditioning [ 15 ] have both been successfully tested in laboratory environments. While remote renal ischemic pre- and postconditioning have also been investigated in a clinical setting, no consistent effect has been reported [ 16 ].…”

Section: Discussionmentioning

confidence: 99%

Dose and timing of injections for effective cyclosporine A pretreatment before renal ischemia reperfusion in mice

et al. 2017

View full text Add to dashboard Cite

BackgroundThere is experimental evidence that lethal ischemia-reperfusion injury (IRI) is largely due to mitochondrial permeability transition pore (mPTP) opening, which can be prevented by cyclosporine A (CsA). The aim of our study is to show that a higher dose of CsA (10 mg/kg) injected just before ischemia or a lower dose of CsA (3 mg/kg) injected further in advance of ischemia (1 h) protects the kidneys and improves mitochondrial function.MethodsAll mice underwent a right unilateral nephrectomy followed by 30 min clamping of the left renal artery. Mice in the control group did not receive any pharmacological treatment. Mice in the three groups treated by CsA were injected at different times and with different doses, namely 3 mg/kg 1 h or 10 min before ischemia or 10 mg/kg 10 min before ischemia. After 24 h of reperfusion, the plasma creatinine level were measured, the histological score was assessed and mitochondria were isolated to calculate the calcium retention capacity (CRC) and level of oxidative phosphorylation.ResultsMortality and renal function was significantly higher in the CsA 10 mg/kg-10 min and CsA 3mg/kg-1 h groups than in the CsA 3mg/kg-10 min group. Likewise, the CRC was significantly higher in the former two groups than in the latter, suggesting that the improved renal function was due to a longer delay in the opening of the mPTP. Oxidative phosphorylation levels were also higher 24 h after reperfusion in the protected groups.ConclusionsOur results suggest that the protection afforded by CsA is likely limited by its availability. The dose and timing of the injections are therefore crucial to ensure that the treatment is effective, but these findings may prove challenging to apply in practice.

show abstract

Section: Discussionmentioning

confidence: 99%

Dose and timing of injections for effective cyclosporine A pretreatment before renal ischemia reperfusion in mice

et al. 2017

View full text Add to dashboard Cite

show abstract

“…11 13 Although not as extensively evaluated, there is also reason for concern regarding the selective publication of preclinical animal studies. [14][15][16] As in clinical research, systematic review and meta-analysis has been instrumental in making publication bias in animal research transparent. Between 46% and 62% of preclinical systematic reviews find evidence of publication bias.…”

Section: Introductionmentioning

confidence: 99%

Publication rate in preclinical research: a plea for preregistrationPublication rate in preclinical research: a plea for preregistration

Naald¹,

Wenker²,

Doevendans³

et al. 2020

BMJ Open Science

View full text Add to dashboard Cite

ObjectivesThe ultimate goal of biomedical research is the development of new treatment options for patients. Animal models are used if questions cannot be addressed otherwise. Currently, it is widely believed that a large fraction of performed studies are never published, but there are no data that directly address this question.MethodsWe have tracked a selection of animal study protocols approved in the University Medical Center Utrecht in the Netherlands, to assess whether these have led to a publication with a follow-up period of 7 years.ResultsWe found that 60% of all animal study protocols led to at least one publication (full text or abstract). A total of 5590 animals were used in these studies, of which 26% was reported in the resulting publications.ConclusionsThe data presented here underline the need for preclinical preregistration, in view of the risk of reporting and publication bias in preclinical research. We plea that all animal study protocols should be prospectively registered on an online, accessible platform to increase transparency and data sharing. To facilitate this, we have developed a platform dedicated to animal study protocol registration: www.preclinicaltrials.eu.

show abstract

“…Exosomes, the best characterized type of EVs; are secreted nanovesicles (30–150nm in diameter) that contain proteins, lipids, mRNA and miRNAs [ 12 ]. Secreted exosomes interconnect cells, and convey the metabolic state of the originating cells, including protective responses to hypoxia [ 13 – 15 ]. For example, we have showed that renal exosomes released from hypoxia pre-conditioned renal tubular cells (i.e., HPC exosomes) prevented most manifestations of severe AKI [ 11 ].…”

Section: Introductionmentioning

confidence: 99%

Human extracellular microvesicles from renal tubules reverse kidney ischemia-reperfusion injury in rats

Dominguez

Xie

et al. 2018

PLoS ONE

View full text Add to dashboard Cite

Hypoxic acute kidney injury, a major unresolved problem, initiates, or aggravates, renal functional and structural decline. There is no treatment for hypoxic acute renal injury and its sequelae. We tested the hypothesis that human kidney tubular cells, or their extracellular vesicles (exosomes), prevent renal injury when infused intravenously 24 hours after 50 minutes of bilateral renal ischemia in Nude rats. Cells and their exosomes were from harvested human kidneys declined for transplantation. Injections of either cells or exosomes, given after 24 and 48 hours of reperfusion, preserved renal function and structure in both treatment groups. However, exosomes were superior to cells; and maintained renal vascular and epithelial networks, prevented renal oxidant stress, and apoptosis; and restrained activation of pro-inflammatory and pro-fibrogenic pathways. Exosomes worked in 24 hours, consistent with functional rather than regenerative activity. Comprehensive proteomic analysis identified 6152 renal proteins from all cellular compartments; and 628 were altered by ischemia at all cell levels, while 377 were significantly improved by exosome infusions. We conclude that renal damage from severe ischemia was broad, and human renal exosomes prevented most protein alterations. Thus, exosomes seem to acutely correct a critical and consequential abnormality during reperfusion. In their absence, renal structure and cells transition to a chronic state of fibrosis and extensive renal cell loss.

show abstract

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

Cited by 24 publications

References 56 publications

Dose and timing of injections for effective cyclosporine A pretreatment before renal ischemia reperfusion in mice

Dose and timing of injections for effective cyclosporine A pretreatment before renal ischemia reperfusion in mice

Publication rate in preclinical research: a plea for preregistrationPublication rate in preclinical research: a plea for preregistration

Human extracellular microvesicles from renal tubules reverse kidney ischemia-reperfusion injury in rats

Contact Info

Product

Resources

About