Role of Cellular Cholesterol in Pharmacologic Preconditioning with Cyclosporine in Experimental Kidney Transplantation

Shihab, Fuad S.; Bennett, William M.; Andoh, Takeshi F.

doi:10.1159/000259900

Cited by 3 publications

(16 citation statements)

References 52 publications

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“…From 1267 citations, 18 studies were eligible for this review (Figure 1) and included descriptions of >500 animals (Table 1). [23][24][25][37][38][39][40][41][42][43][44][45][46][47][48][49][50][51] κ agreement for study selection was 0.77. All studies were published between 1991 and 2020.…”

Section: Study Selectionmentioning

confidence: 99%

“…Most studies (16/18; 89%) used rat models of organ transplantation, [23][24][25][38][39][40][41][42][43][44][45][46][48][49][50][51] whereas 2 studies used pigs (Table 1). 37,47 The specific organ of interest varied and included kidney (8 studies), 23,25,[37][38][39][40][41][42] liver (6 studies), [43][44][45][46][47][48] bowel (3 studies), 24,50,51 and lung (1 study). 49 Table 1 lists the CNI regimens.…”

Section: Study Characteristicsmentioning

confidence: 99%

“…[23][24][25]38,40,42,[44][45][46][49][50][51] Eleven studies (61%) administered a single dose. 24,25,38,[40][41][42][43]46,48,50,51 The principal routes of administration were intravenous (8/18 studies; 44%), 23,24,38,40,42,46,50,51 enteral (4 studies; 22%), 37,39,43,48 intraperitoneal (2 studies; 11%), 25,41 and intramuscular (2 studies; 11%). 45,47 The timing of CNI therapy initiation varied between studies.…”

Section: Study Characteristicsmentioning

confidence: 99%

“…37 All studies included a CIT of >2 h. In kidney transplant studies, the mean (SD) CIT was 7.9 (9.5) h, 23,25,[37][38][39]41,42 and the mean (SD) warm ischemic time was 29 (15.6) min. 25,37,39,41 In liver transplantation, the mean (SD) CIT was 9.4 (10.8) h, [43][44][45][46][47] and warm ischemic time was 28.7 (27.2) min. [43][44][45] Nine studies (50%) did not report supportive care for recipients.…”

Section: Clinical Relevancementioning

confidence: 99%

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Calcineurin Inhibition in Deceased Organ Donors: A Systematic Review and Meta-analysis of Preclinical Studies

D’Aragon,

Rousseau,

Breau

et al. 2023

Transplantation Direct

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Background. Preconditioning deceased organ donors with calcineurin inhibitors (CNIs) may reduce ischemia–reperfusion injury to improve transplant outcomes. Methods. We searched MEDLINE, EMBASE, Cochrane Library, and conference proceedings for animal models of organ donation and transplantation, comparing donor treatment with CNIs with either placebo or no intervention, and evaluating outcomes for organ transplantation. Reviewers independently screened and selected studies, abstracted data, and assessed the risk of bias and clinical relevance of included studies. Where possible, we pooled results using meta-analysis; otherwise, we summarized findings descriptively. Results. Eighteen studies used various animals and a range of CNI agents and doses and evaluated their effects on a variety of transplant outcomes. The risk of bias and clinical applicability were poorly reported. Pooled analyses suggested benefit of CNI treatment on early graft function in renal transplants (3 studies; serum creatinine: ratio of means [RoM] 0.54; 95% confidence interval [CI], 0.34-0.86) but not for liver transplants (2 studies; serum alanine transaminase: RoM 0.61; 95% CI, 0.30-1.26; and serum aspartate aminotransferase: RoM 0.58; 95% CI, 0.26-1.31). We found no reduction in graft loss at 7 d (2 studies; risk ratio 0.54; 95% CI, 0.08-3.42). CNI treatment was associated with reduced transplant recipient levels of interleukin-6 (4 studies; RoM 0.36; 95% CI, 0.19-0.70), tumor necrosis factor-alpha (5 studies; RoM 0.36; 95% CI, 0.12-1.03), and cellular apoptosis (4 studies; RoM 0.30; 95% CI, 0.19-0.47). Conclusions. Although this compendium of animal experiments suggests that donor preconditioning with CNIs may improve early kidney graft function, the limited ability to reproduce a true clinical environment in animal experiments and to assess for risk of bias in these experiments is a serious weakness that precludes current clinical application.

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Section: Study Selectionmentioning

confidence: 99%

Section: Study Characteristicsmentioning

confidence: 99%

Section: Study Characteristicsmentioning

confidence: 99%

Section: Clinical Relevancementioning

confidence: 99%

See 2 more Smart Citations

Calcineurin Inhibition in Deceased Organ Donors: A Systematic Review and Meta-analysis of Preclinical Studies

D’Aragon,

Rousseau,

Breau

et al. 2023

Transplantation Direct

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“…The responsible mechanism appears not to be, as expected, an additional inhibition of the alloimmune response. An effect on renal I/R injury is more likely, because the protective effects have been observed in syngeneic kidney transplant models and appear related to acute renal stress .…”

Section: Donor Pre‐treatmentmentioning

confidence: 99%

Donor pre‐treatment in clinical kidney transplantation: a critical appraisal

Vries

Wijermars

Reinders

et al. 2013

Clinical Transplantation

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Kidney transplantation represents one of the medical achievements of the 20th century. However, its continued success is limited by the increasing shortage of donor grafts. As a result, more kidney grafts from marginal donors are being considered for transplantation, with concomitantly more initial graft injury and limited organ and patient survival. This has led to an increased need for interventions aiming to optimize and preserve graft quality. Interventions within the donor may protect against ischemia/reperfusion injury, and therefore, donor pre-treatment is a promising strategy to increase graft function and survival. During the last decade, diverse donor pre-treatment interventions have been explored in animal studies. Moreover, the first human trials concerning donor pre-treatment in kidney transplantation have provided encouraging results. Unfortunately, it remains difficult to determine how and where to intervene in the multifactorial and complex processes that affect the donor kidney. Moreover, ethical matters play a critical role in donor interventions, and pre-treatment should principally not have any potentially unfavorable effects on other organs to be transplanted or on the living donor. This review provides an overview of promising therapeutical strategies for donor pre-treatment in kidney transplantation and discusses the clinical trials that have been conducted thus far.

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Effects of cyclosporine A pretreatment of deceased organ donors on kidney graft function (Cis-A-rein): study protocol for a randomized controlled trial

Orban

Fontaine

Cassuto

et al. 2018

Trials

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BackgroundRenal transplantation represents the treatment of choice of end-stage kidney disease. Delayed graft function (DGF) remains the most frequent complication after this procedure, reaching more than 30%. Its prevention is essential as it impedes early- and long-term prognosis of transplantation. Numerous pharmacological interventions aiming to prevent ischemia-reperfusion injuries failed to reduce the rate of DGF. We hypothesize that cyclosporine as an early preconditioning procedure in donors would be associated with decreased DGF.MethodsThe Cis-A-rein study is an investigator-initiated, prospective, multicenter, double-blind, randomized, controlled study performed to assess the effects of a donor preconditioning with cyclosporine A on kidney grafts function in transplanted patients. After randomization, a brain dead donor will receive 2.5 mg kg−1 of cyclosporine A or the same volume of 5% glucose solution. The primary objective is to compare the rate of DGF, defined as the need for at least one dialysis session within the 7 days following transplantation, between both groups. The secondary objectives include rate of slow graft function, mild and severe DGF, urine output and serum creatinine during the first week after transplantation, rate of primary graft dysfunction, renal function and mortality at 1 year. The sample size (n = 648) was determined to obtain 80% power to detect a 10% difference for rate of DGF at day 7 between the two groups (30% of the patients in the placebo group and 20% of the patients in the intervention group).DiscussionDelayed graft function is a major issue after renal transplantation, impeding long-term prognosis. Cyclosporine A pretreatment in deceased donors could improve the outcome of patients after renal transplantation.Trial registrationClinicalTrials.gov, ID: NCT02907554 Registered on 20 September 2016. Electronic supplementary materialThe online version of this article (10.1186/s13063-018-2597-4) contains supplementary material, which is available to authorized users.

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Role of Cellular Cholesterol in Pharmacologic Preconditioning with Cyclosporine in Experimental Kidney Transplantation

Cited by 3 publications

References 52 publications

Calcineurin Inhibition in Deceased Organ Donors: A Systematic Review and Meta-analysis of Preclinical Studies

Calcineurin Inhibition in Deceased Organ Donors: A Systematic Review and Meta-analysis of Preclinical Studies

Donor pre‐treatment in clinical kidney transplantation: a critical appraisal

Effects of cyclosporine A pretreatment of deceased organ donors on kidney graft function (Cis-A-rein): study protocol for a randomized controlled trial

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