The Transplant Evidence Alert provides a monthly overview of the 10 most important new clinical trials in organ transplantation, selected and reviewed by the Peter Morris Centre for Evidence in Transplantation (Oxford University).
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BMJ Open Sport Exerc Med. 2023 Jul 9;9(3):e001331 doi: 10.1136/bmjsem-2022-001331.
CET Conclusion
OBJECTIVES:
High-intensity interval training (HIT) improves peak oxygen consumption (VO2peak) in de novo heart transplant (HTx) recipients. It remains unclear whether this improvement early after HTx is solely dependent on peripheral adaptations, or due to a linked chain of central and peripheral adaptations. The objective of this study was to determine whether HIT results in structural and functional adaptations in the cardiovascular system. METHODS:Eighty-one de novo HTx recipients were randomly assigned to participate in either 9 months of supervised HIT or standard care exercise-based rehabilitation. Cardiac function was assessed by echocardiogram and the coronary microcirculation with the index of microcirculatory resistance (IMR) at baseline and 12 months after HTx. RESULTS:Cardiac function as assessed by global longitudinal strain was significantly better in the HIT group than in the standard care group (16.3±1.2% vs 15.6±2.2%, respectively, treatment effect = -1.1% (95% CI -2.0% to -0.2%), p=0.02), as was the end-diastolic volume (128.5±20.8 mL vs 123.4±15.5 mL, respectively, treatment effect=4.9 mL (95% CI 0.5 to 9.2 mL), p=0.03). There was a non-significant tendency for IMR to indicate improved microcirculatory function (13.8±8.0 vs 16.8±12.0, respectively, treatment effect = -4.3 (95% CI -9.1 to 0.6), p=0.08). CONCLUSION:When initiated early after HTx, HIT leads to both structural and functional cardiovascular adaptations. TRIAL REGISTRATION NUMBER:NCT01796379. |
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Br J Clin Pharmacol. 2023 Dec;89(12):3629-3636 doi: 10.1111/bcp.15871.
CET Conclusion
AIMS:
Ischemia-reperfusion injury (IRI) during kidney transplant procedures is associated with adverse outcome. Alkaline phosphatase (AP) is an enzyme that has the potential to dampen IRI. Prior to this study, it had not been tested in the setting of kidney transplantation. This study aimed to evaluate the safety and feasibility of peri-procedural AP administration in living donor kidney transplantation. METHODS:In this double blind, randomized, placebo-controlled, single-center pilot study, all eligible recipients of living donor kidneys were asked to give informed consent. AP (bRESCAP) or a placebo was administered intravenously over 24 hours after the transplantation procedure. The primary outcome-graft function at 1 year-was represented by iohexol measured glomerular filtration rate (mGFR). Serum and urine biomarkers within seven days after surgery were used as surrogate markers of kidney function and injury. RESULTS:Eleven patients were enrolled of whom five were treated with bRESCAP and six with placebo. After 1 year, mGFR was not different between groups. No specific adverse events were observed in the bRESCAP group. Urine expression of injury biomarkers CCL14, NGAL and Cystatin C was lower in the bRESCAP group at day seven. This was statistically significant. CONCLUSION:This study illustrates that bRESCAP treatment is feasible in kidney transplantation, might have a dampening effect on IRI induced renal inflammation, and raises no safety concerns. Future research will evaluate the effects of bRESCAP treatment in donation after circulatory death kidney transplantation where IRI is more pronounced. |
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Hernia. 2023 Sep 15; doi: 10.1007/s10029-023-02879-9.
CET Conclusion
PURPOSE:
Incisional hernia (IH) post renal transplant (RT) is relatively uncommon and can be challenging to manage clinically due to the presence of the kidney graft and patient immunosuppression. This systematic review and meta-analysis synthesises the current literature in relation to IH rates, risk factors and outcomes post RT. METHODS:PubMed, EMBASE, and Cochrane Central Registry of Controlled Trials (CENTRAL) were searched up to July 2023. The most up to date Preferred Reporting Items for Systematic Reviews and Meta Analyses guidelines were followed. Pertinent clinical information was synthesised. A meta-analysis of the pooled proportions of IH rates, the rates of patients requiring surgical repair and the rates of recurrence post RT are reported. RESULTS:Twenty studies comprising 16,018 patients were included in this analysis. The pooled rate of IH occurrence post RT was 4% (CI 3-5%). The pooled rate of IH repair post RT was 61% (CI 14-100%). The pooled rate of IH recurrence after repair was 16% (CI 9-23%). Risk factors identified for IH development post RT are BMI, immunosuppression, age, smoking, incision type, reoperation, concurrent abdominal wall hernia, lymphocele formation and pulmonary disease. CONCLUSIONS:IH post RT is uncommon and the majority of IH post RT are repaired surgically on an elective basis. |
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Transplantation. 2023 Aug 30; doi: 10.1097/TP.0000000000004776.
CET Conclusion
BACKGROUND:
Evidence on the optimal maintenance of immunosuppressive regimen in kidney transplantation recipients is limited. METHODS:The Amsterdam, LEiden, GROningen trial is a randomized, multicenter, investigator-driven, noninferiority, open-label trial in de novo kidney transplant recipients, in which 2 immunosuppression minimization strategies were compared with standard immunosuppression with basiliximab, corticosteroids, tacrolimus, and mycophenolic acid. In the minimization groups, either steroids were withdrawn from day 3, or tacrolimus exposure was reduced from 6 mo after transplantation. The primary endpoint was kidney transplant function at 24 mo. RESULTS:A total of 295 participants were included in the intention-to-treat analysis. Noninferiority was shown for the primary endpoint; estimated glomerular filtration rate at 24 mo was 45.3 mL/min/1.73 m2 in the early steroid withdrawal group, 49.0 mL/min/1.73 m2 in the standard immunosuppression group, and 44.7 mL/min/1.73 m2 in the tacrolimus minimization group. Participants in the early steroid withdrawal group were significantly more often treated for rejection (P = 0.04). However, in this group, the number of participants with diabetes mellitus during follow-up and total cholesterol at 24 mo were significantly lower. CONCLUSIONS:Tacrolimus minimization can be considered in kidney transplant recipients who do not have an increased immunological risk. Before withdrawing steroids the risk of rejection should be weighed against the potential metabolic advantages. |
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BMJ Open. 2023 Jul 27;13(7):e072805 doi: 10.1136/bmjopen-2023-072805.
CET Conclusion
INTRODUCTION:
Kidney transplant candidates (KTCs) need to be in optimal physical and psychological condition prior to surgery. However, KTCs often experience compromised functional capacity which can be characterised as frailty. Prehabilitation, the enhancement of a person's functional capacity, may be an effective intervention to improve the health status of KTCs. The PREhabilitation of CAndidates for REnal Transplantation (PreCareTx) study aims to examine the effectiveness of a multimodal prehabilitation programme on the health status of KTCs, and to explore the potential of implementation of prehabilitation in daily clinical practice. METHODS AND ANALYSIS:This study uses a single centre, effectiveness-implementation hybrid type I study design, comprised of a randomised controlled trial and a mixed-methods study. Adult patients who are currently on the transplant waiting list or are waitlisted during the study period, at a university medical centre in The Netherlands, will be randomly assigned to either prehabilitation (n=64) or care as usual (n=64) groups. The prehabilitation group will undergo a 12-week home-based, tailored prehabilitation programme consisting of physical and/or nutritional and/or psychosocial interventions depending on the participant's deficits. This programme will be followed by a 12-week maintenance programme in order to enhance the incorporation of the interventions into daily life. The primary endpoint of this study is a change in frailty status as a proxy for health status. Secondary endpoints include changes in physical fitness, nutritional status, psychological well-being, quality of life and clinical outcomes. Tertiary endpoints include the safety, feasibility and acceptability of the prehabilitation programme, and the barriers and facilitators for further implementation. ETHICS AND DISSEMINATION:Medical ethical approval was granted by the Medical Ethics Committee Groningen, Netherlands (M22.421). Written informed consent will be obtained from all participants. The results will be disseminated at international conferences and in peer-reviewed journals. TRIAL REGISTRATION NUMBER:ClinicalTrials.gov, NCT05489432. |
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Front Nephrol. 2023 May 15;3:1181076 doi: 10.3389/fneph.2023.1181076.
CET Conclusion
BACKGROUND:
Focal segmental glomerulosclerosis (FSGS) is a common cause of end-stage kidney disease requiring kidney transplantation and can recur in the allograft in 30-80% of recipients resulting in reduced graft survival. Plasmapheresis has shown efficacy in treating some cases of recurrent FSGS but isolated plasmapheresis has not demonstrated efficacy in preventing recurrent FSGS. Rituximab has had anecdotal success in preventing recurrence in a single center study but has not been studied in combination with plasmapheresis for preventing FSGS recurrence. METHODS:We are conducting a randomized, controlled, multicenter clinical trial of adult and pediatric kidney transplant recipients with primary FSGS to assess whether plasmapheresis in combination with rituximab prevents recurrent disease post-transplantation. DISCUSSION:Rituximab combined with plasmapheresis is a promising, novel therapy to prevent recurrent FSGS, a disease with limited therapeutic options and no consensus guidelines for prevention or treatment. CLINICAL TRIAL REGISTRATION:https://clinicaltrials.gov/ct2/show/NCT03763643, identifier NCT03763643. |
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Physiol Int. 2023 Aug 28;110(3):211-226 doi: 10.1556/2060.2023.00211.
CET Conclusion
BACKGROUND:
Acute and chronic hepatic failure can lead to increased mortality in critically ill and perioperative patients. Understanding the pathophysiological principles of these conditions in critically ill patients is of great importance to reduce mortality. The aim of our systematic literature review was to identify all randomized controlled trials on any intervention that had a statistically significant documented reduction in mortality in patients with hepatic failure. METHODS:We searched PubMed, Scopus and Embase databases for pertinent studies on January 1st 2021. The following studies were included: randomized controlled trials; studies investigating adult critically ill or perioperative patient populations with any form of hepatic failure; mortality as primary or secondary outcome; and statistically significant differences in mortality between the examined groups. RESULTS:We finally found nine trials in our systematic review on the effect of antibiotic administration and infectious diseases among patients with cirrhosis (three studies); immune modulation after liver transplantation (one study); administration of colloids in cirrhotic patients (one study); the effect of high-volume plasma exchange in acute liver failure (one study); administration of N-acetylcysteine in acute liver failure (one study); and treatment with terlipressin (two studies). CONCLUSION:In the present review we found only nine randomized studies with a documented survival benefit in patients with liver failure. Strategies that most improved mortality were associated with the outcome of sepsis and renal function. |
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Crit Care Sci. 2023 Mar 1;35(1):11-18 doi: 10.5935/2965-2774.20230336-en.
CET Conclusion
OBJECTIVE:
To explain the rationale and protocol of the methods and analyses to be used in the LIVER-PAM randomized clinical trial, which seeks to understand whether a higher mean arterial pressure is capable of reducing the incidence of renal dysfunction postoperatively after liver transplantation. METHODS:LIVER-PAM is an open-label, randomized, controlled, singlecenter clinical trial. Patients randomized to the intervention group will have a mean arterial pressure of 85 - 90mmHg in the initial 24 hours of postoperative management, while patients in the control group will have a mean arterial pressure of 65 - 70mmHg in the same period. A sample of 174 patients will be required to demonstrate a 20% reduction in the absolute incidence of renal dysfunction, with a power of 80% and an alpha of 0.05. CONCLUSION:If a 20% reduction in the absolute incidence of renal dysfunction in the postoperative period of liver transplantation is achieved with higher target mean arterial pressure in the first 24 hours, this would represent an inexpensive and simple therapy for improving current outcomes in the management of liver transplant patients.ClinicalTrials.gov Registry: NCT05068713. |
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World J Transplant. 2023 Jun 18;13(4):190-200 doi: 10.5500/wjt.v13.i4.190.
CET Conclusion
BACKGROUND:
The Hispanic community has a high demand for organ donation but a shortage of donors. Studies investigating factors that could promote or hinder organ donation have examined emotional video interventions. Factors acting as barriers to organ donation registration have been classified as: (1) Bodily integrity; (2) medical mistrust; (3) "ick"-feelings of disgust towards organ donation; and (4) "jinx"-fear that registration may result in one dying due to premeditated plans. We predict that by providing necessary information and education about the donation process via a short video, individuals will be more willing to register as organ donors. AIM:To determine perceptions and attitudes regarding barriers and facilitators to organ donation intention among Hispanic residents in the New York metro politan area. METHODS:This study was approved by the Institutional Review Board at Northwell Health. The approval reference number is No. 19-0009 (as presented in Supplementary material). Eligible participants included Hispanic New York City (NYC) residents, 18 years of age and above, who were recruited voluntarily through Cloud Research and participated in a larger randomized survey study of NYC residents. The survey an 85-item Redcap survey measured participant demographics, attitudes, and knowledge of organ donation as well as the intention to register as an organ donor. Attention checks were implemented throughout the survey, and responses were excluded for those who did fail. Participants were randomly assigned two-between subject conditions: To view a short video on organ donation and then proceed to complete the survey (i.e., video first) and view the same video at the end of the survey (video last). No intra-group activities were conducted. This study utilized an evidenced-based emotive educational intervention (video) which was previously utilized and was shown to increase organ donation registration rates at the Ohio Department of Motor Vehicles. Results were analyzed using Jamovi statistical software. Three hundred sixty-five Hispanic individuals were included in the analysis. Once consent was obtained and participants entered the survey (the survey sample is presented in Supplementary material), participants were asked to report on demographic variables and their general impression of organ donation after death. The video depicted stories regarding organ donation after death from various viewpoints, including from the loved ones of a deceased person who died waiting for a transplant; from the loved ones of a deceased person whose organs were donated upon death; and, from those who were currently waiting for a transplant. RESULTS:Using a binomial logistic regression, the analysis provides information about the relationship between the effects of an emotive video and the intention to donate among Hispanic participants who were not already registered as donors. The willingness to go back and register was found to be significantly more probable for those who watched the emotive video before being asked about their organ donation opinions (odds ratio: 2.05, 95% confidence interval: 1.06-3.97). Motivations for participation in organ donation were also captured with many stating the importance of messages coming from "people like me" and a message that highlights "the welfare of those in need". Overall, the findings suggest that using an emotive video that addresses organ donation barriers to prompt organ donation intentions can be effective among the Hispanic populous. Future studies should explore using targeted messaging that resonates with specific cultural groups, highlighting the welfare of others. CONCLUSION:This study suggests that an emotive educational intervention is likely to be effective in improving organ donation registration intent among the Hispanic population residing in NYC. |