Barriers and facilitators to physical activity: A comparative analysis of transplant athletes competing in high intensity sporting events with other transplant recipients.

BACKGROUND: There is widespread recognition that many transplant recipients struggle to become and remain physically active. However, some transplant recipients do undertake strenuous training and significant physical activity (PA) and participate in intensive sports. AIM: This study sought to understand facilitators and barriers to be physically active for Transplant Athletes (TXA) compared to a group of Dutch transplantees. This explorative mixed methods study analysed race performance and interview data from TxA who participated in cycling and/or the sprint triathlon at the World Transplant Games 2023, and compared their lived experiences in terms of barriers and facilitators of PA with those of 16 transplantees in a study from the Netherlands previously published in this journal. METHODS: Using Patient and Public Involvement and engagement (PPI), race data from World Transplant Games 2023 and subsequent in-depth interviews were used from 27 TxA. A visual artefact of barriers and facilitators from the previous Dutch study was used to prompt identification and discussion of barriers and facilitators of PA. Interview data were coded by three coders. RESULTS: Many of the barriers to PA previously reported by Dutch transplant recipients were not shared by the majority of TxA in this study. The TxA in this study reported significantly lower physical limitations, lower fear to undertake exercise, and no comorbidity issues for TxA. Furthermore, TxA perceived they received substantial social support, had the strength to do PA, and were in control of their weight. CONCLUSION: Several TxA reported a lack of understanding from medical and other professionals about the appropriate intensity of PA. An evidence-based framework of PA for transplant recipients and transplant athletes is needed for safe and appropriate PA.

Removing the physician from the equation: Patient-controlled, home-based therapeutic drug self-monitoring of tacrolimus.

The dosing of tacrolimus, which forms the backbone of immunosuppressive therapy after kidney transplantation, is complex. This is due to its variable pharmacokinetics (both between and within individual patients), narrow therapeutic index, and the severe consequences of over- and underexposure, which may cause toxicity and rejection, respectively. Tacrolimus is, therefore, routinely dosed by means of therapeutic drug monitoring (TDM). TDM is performed for as long as the transplant functions and frequent and often lifelong sampling is therefore the rule. This puts a significant burden on patients and transplant professionals and is associated with high healthcare-associated costs. Furthermore, by its very nature, TDM is reactive and has no predictive power. Finally, the current practice of TDM does not foresee in an active role for patients themselves. Rather, the physician or pharmacist prescribes the next tacrolimus dose after obtaining the concentration measurement test results. In this article, we propose a strategy of patient-controlled, home-based, self-TDM of the immunosuppressant tacrolimus after transplantation. We argue that with the combined use of population tacrolimus pharmacokinetic models, home-based sampling by means of dried blood spotting and implementation of telemedicine, this may become a feasible approach in the near future.

Public Opinions on Removing Disincentives and Introducing Incentives for Organ Donation: Proposing a European Research Agenda.

The shortage of organs for transplantations is increasing in Europe as well as globally. Many initiatives to the organ shortage, such as opt-out systems for deceased donation and expanding living donation, have been insufficient to meet the rising demand for organs. In recurrent discussions on how to reduce organ shortage, financial incentives and removal of disincentives, have been proposed to stimulate living organ donation and increase the pool of available donor organs. It is important to understand not only the ethical acceptability of (dis)incentives for organ donation, but also its societal acceptance. In this review, we propose a research agenda to help guide future empirical studies on public preferences in Europe towards the removal of disincentives and introduction of incentives for organ donation. We first present a systematic literature review on public opinions concerning (financial) (dis)incentives for organ donation in European countries. Next, we describe the results of a randomized survey experiment conducted in the United States. This experiment is crucial because it suggests that societal support for incentivizing organ donation depends on the specific features and institutional design of the proposed incentive scheme. We conclude by proposing this experiment's framework as a blueprint for European research on this topic.

European Consensus on the Management of Sensitized Kidney Transplant Recipients: A Delphi Study.

An increasing number of sensitized patients awaiting transplantation face limited options, leading to fatalities during dialysis and higher costs. The absence of established evidence highlights the need for collaborative consensus. Donor-specific antibodies (DSA)-triggered antibody-mediated rejection (AMR) significantly contributes to kidney graft failure, especially in sensitized patients. The European Society for Organ Transplantation (ESOT) launched the ENGAGE initiative, categorizing sensitized candidates by AMR risk to improve patient care. A systematic review assessed induction and maintenance regimens as well as antibody removal strategies, with statements subjected to the Delphi methodology. A Likert-scale survey was distributed to 53 European experts (Nephrologists, Transplant surgeons and Immunologists) with experience in kidney transplant recipient care. A rate ≥75% with the same answer was considered consensus. Consensus was achieved in 95.3% of statements. While most recommendations aligned, two statements related to complement inhibitors for AMR prophylaxis lacked consensus. The ENGAGE consensus presents contemporary recommendations for desensitization and immunomodulation strategies, grounded in predefined risk categories. The adoption of tailored, patient-specific measures is anticipated to streamline the care of sensitized recipients undergoing renal allografts. While this approach holds the promise of enhancing transplant accessibility and fostering long-term success in transplantation outcomes, its efficacy will need to be assessed through dedicated studies.

What are the benefits of preemptive versus non-preemptive kidney transplantation? A systematic review and meta-analysis.

Opting for a preemptive kidney transplant (PKT) can help avoid costs and morbidity associated with dialysis. However, while multiple studies have shown clinical benefits of PKT, other studies have not demonstrated this, leading to controversy in the literature regarding the exact benefits of PKT. Therefore, this study aimed to determine the clinical outcomes of PKT versus non-preemptive kidney transplantation (nPKT) in adult patients. Multiple databases were searched up to May 4, 2022. Independent reviewers selected studies for inclusion and extracted relevant data. Risk of bias was assessed using the Downs and Black checklist. Eighty-seven studies including 859,715 adult kidney transplant patients were included the review. The risk of patient death (relative risk [95% confidence interval] 0.74 [0.60-0.91]) was significantly lower in PKT versus nPKT patients for living donor (LD) transplants, whereas the risk of overall graft loss was significantly lower in PKT compared to nPKT patients for both LD (0.72 [0.62-0.83]) as well as deceased donor (DD) transplants (0.80 [0.69-0.92]). The evidence suggests that LD PKT patients have a lower risk of patient death and graft loss compared to nPKT patients, and DD PKT patients have a lower risk of graft loss than nPKT patients.

Trends in systematic reviews of kidney transplantation: A 10-year analysis of the evidence base.

BACKGROUND: Systematic reviews (SRs) are the highest form of evidence for all types of clinical questions in evidence-based practice. For the first time in 2018, the number of SRs in transplantation outstripped those from randomised controlled trials (RCTs). This raises concerns of duplication or increased use of non-RCT evidence. We aimed to analyse the trends, strength and quality of SRs in kidney transplantation over a 10-year period. METHODS: SRs in kidney transplantation were identified from the Transplant Library, without language restriction. All full-text citations were exported to a custom Research Electronic Data Capture (REDCap) database prior to evaluation. Quality of evidence in all included SRs was assessed using AMSTAR-2. RESULTS: We included 454 SRs, of which, only three were scored as 'high quality'. We found that 96.70% of SRs were identified as 'critically low quality', which increased in number over time. We also found that inclusion of non-RCT data increased in the most recent 5 years. Only 14.12% of SRs had made a clear recommendation for practice. CONCLUSIONS: This review highlights several concerning statistics that need to be addressed. In the last 10 years, only three SRs in kidney transplantation were 'high-quality'. The weaknesses identified in critical domains, alongside the increased use of non-RCT data and lack of conclusive recommendations undermines the confidence in the results of the SRs and purpose of publication. As these SRs are instrumental to clinical decision-making and patient care in kidney transplantation, we advocate for improved reporting quality among SRs in kidney transplantation.

Clinical impact of early post-transplant red cell transfusions in kidney transplantation: a systematic review and meta-analysis.

Introduction: Red blood cell transfusions (RBCT) represent a potentially modifiable risk factor for HLA sensitisation and adverse outcomes post transplantation. Evidence of the clinical impact of post-transplant RBCT has been infrequently reported. Herein, we performed a systematic review of available literature to assess the prevalence of RBCT post kidney transplant, and the effect of transfusion on transplant outcomes. Methods: We included studies from 2000 to July 2022, published on Medline, Embase and the Transplant Library. Results: Ten studies were analysed which included a total of 32,817 kidney transplant recipients, with a median transfusion prevalence of 40% (range 18-64%). There was significant heterogeneity between studies in terms of patient and allograft characteristics, immunological risk, and immunosuppression protocols. Analysis of unadjusted outcomes showed that post-transplant RBCTs are associated with inferior patient survival, allograft loss, rejection and donor specific antibodies. Adjusted outcomes were described where available, and supported the adverse associations seen in the unadjusted models in many studies. Discussion: This review demonstrates that RBCT post-transplant are common and maybe associated with inferior outcomes, highlighting the urgent need for high quality prospective evidence of the effect of RBCTs on transplant outcomes. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, identifier, CRD42022348763767.

Is Preemptive Kidney Transplantation Associated With Improved Outcomes when Compared to Non-preemptive Kidney Transplantation in Children? A Systematic Review and Meta-Analysis.

Main Problem: Preemptive kidney transplantation (PKT) is performed prior to dialysis initiation to avoid dialysis-related morbidity and mortality in children and adolescents. We undertook a systematic review to compare clinical outcomes in PKT versus kidney transplantation after dialysis initiation in paediatric patients. Methods: The bibliographic search identified studies that compared paediatric recipients of a first or subsequent, living or deceased donor PKT versus non-preemptive kidney transplant. Methodological quality was assessed for all studies. Data were pooled using the random-effects model. Results: Twenty-two studies (n = 22,622) were included. PKT reduced the risk of overall graft loss (relative risk (RR) .57, 95% CI: .49-.66) and acute rejection (RR: .81, 95% CI: .75-.88) compared to transplantation after dialysis. Although no significant difference was observed in overall patient mortality, the risk of patient death was found to be significantly lower in PKT patients with living donor transplants (RR: .53, 95% CI: .34-.83). No significant difference was observed in the incidence of delayed graft function. Conclusion: Evidence from observational studies suggests that PKT is associated with a reduction in the risk of acute rejection and graft loss. Efforts should be made to promote and improve rates of PKT in this group of patients (PROSPERO). Systematic Review Registration: https://clinicaltrials.gov/, CRD42014010565.

A systematic review and meta-analyses of regional perfusion in donation after circulatory death solid organ transplantation.

In donation after circulatory death (DCD), (thoraco)abdominal regional perfusion (RP) restores circulation to a region of the body following death declaration. We systematically reviewed outcomes of solid organ transplantation after RP by searching PubMed, Embase, and Cochrane libraries. Eighty-eight articles reporting on outcomes of liver, kidney, pancreas, heart, and lung transplants or donor/organ utilization were identified. Meta-analyses were conducted when possible. Methodological quality was assessed using National Institutes of Health (NIH)-scoring tools. Case reports (13/88), case series (44/88), retrospective cohort studies (35/88), retrospective matched cohort studies (5/88), and case-control studies (2/88) were identified, with overall fair quality. As blood viscosity and rheology change below 20 °C, studies were grouped as hypothermic (HRP, ≤20 °C) or normothermic (NRP, >20 °C) regional perfusion. Data demonstrate that RP is a safe alternative to in situ cold preservation (ISP) in uncontrolled and controlled DCDs. The scarce HRP data are from before 2005. NRP appears to reduce post-transplant complications, especially biliary complications in controlled DCD livers, compared with ISP. Comparisons for kidney and pancreas with ISP are needed but there is no evidence that NRP is detrimental. Additional data on NRP in thoracic organs are needed. Whether RP increases donor or organ utilization needs further research.

Consensus statement on normothermic regional perfusion in donation after circulatory death: Report from the European Society for Organ Transplantation's Transplant Learning Journey.

Normothermic regional perfusion (NRP) in donation after circulatory death (DCD) is a safe alternative to in situ cooling and rapid procurement. An increasing number of countries and centres are performing NRP, a technically and logistically challenging procedure. This consensus document provides evidence-based recommendations on the use of NRP in uncontrolled and controlled DCDs. It also offers minimal ethical, logistical and technical requirements that form the foundation of a safe and effective NRP programme. The present article is based on evidence and opinions formulated by a panel of European experts of Workstream 04 of the Transplantation Learning Journey project, which is part of the European Society for Organ Transplantation.

Managing immunosuppressive therapy in potentially cured post-kidney transplant cancer (excluding non-melanoma skin cancer): an overview of the available evidence and guidance for shared decision-making.

Kidney transplant recipients (KTRs) have increased incidence of de novo cancers. After having undergone treatment for cancer with curative intent, reducing the overall immunosuppressive load and/or switching to an alternative drug regimen may potentially be of great benefit to avoid cancer recurrence, but should be balanced against the risks of rejection and/or severe adverse events. The TLJ (Transplant Learning Journey) project is an initiative from the European Society for Organ Transplantation (ESOT). This article reports a systematic literature search undertaken by TLJ Workstream 3 to answer the questions: (1) Should we decrease the overall anti-rejection therapy in potentially cured post-kidney transplant cancer (excluding non-melanoma skin cancer)? (2) Should we switch to mammalian target of rapamycin inhibitors (mTORi) in potentially cured post-kidney transplant cancer (excluding non-melanoma skin cancer)? The literature search revealed insufficient solid data on which to base recommendations, so this review additionally presents an extensive overview of the indirect evidence on the benefits versus risks of alterations in immunosuppressive medication. We hope this summary will help transplant physicians advise KTRs on how best to continue with anti-rejection therapy after receiving cancer treatment with curative intent, and aid shared decision-making, ensuring that patient preferences are taken into account.

Critical Appraisal of International Clinical Practice Guidelines in Kidney Transplantation Using the Appraisal of Guidelines for Research and Education II Tool: A Systematic Review.

BACKGROUND: Although clinical practice guidelines (CPGs) are used for the development of local protocols in kidney transplantation (Ktx), the quality of their methodology is variable. This systematic review aimed to critically appraise international CPGs in all aspects of Ktx using the Appraisal of Guidelines for Research and Evaluation II tool. METHODS: Clinical Practice Guidelines in Ktx and donation published between 2010 and 2017 were identified from MEDLINE, Embase, National Guideline Clearinghouse, National Health Service and National Institute for Health and Care Excellence Evidence Searches, and the websites of transplant societies. Using Appraisal of Guidelines for Research and Evaluation II, 3 appraisers assessed the quality of CPGs. Interrater reliability was measured using the intraclass correlation coefficient (ICC). RESULTS: Searches identified 3168 records, and 115 CPGs were included. The highest scoring Appraisal of Guidelines for Research and Evaluation II domain was "scope and purpose" (80%; range, 30%-100%), followed by "clarity of presentation" (77%; range, 43%-98%), "editorial independence" (52%; range, 0%-94%), "rigor of development" (47%; range 6%-97%) and "stakeholder involvement" (41%; range, 11%-85%). The poorest scoring domain was "applicability" (31%; range, 3%-74%). Most CPGs were recommended for future use either with (63%) or without (18%) modifications. A small number (14%) were not recommended for future use or reviewers (5%) did not agree on recommending the CPG. The overall mean CPG quality score was 4 of 7 (range, 2-7). The mean ICC of 0.74 indicated substantial agreement between reviewers. CONCLUSIONS: The quality of international CPGs in Ktx was variable, and most CPGs lacked key aspects of methodological robustness and transparency. Improvements in methodology, patient involvement, and strategies for implementation are required.

Systematic Review and Meta-Analysis of Posttransplant Hepatic Artery and Biliary Complications in Patients Treated With Transarterial Chemoembolization Before Liver Transplantation.

BACKGROUND: Hepatic artery complications are feared complications after liver transplantation and may compromise the biliary tract, graft, and patient survival. The objective of this systematic review and meta-analysis was to compare risk of hepatic artery and biliary complications after liver transplantation in patients who underwent neoadjuvant transarterial chemoembolization (TACE) versus no TACE. METHODS: Comprehensive searches were performed in Embase, MEDLINE OvidSP, Web of Science, Google Scholar, and Cochrane databases to identify studies concerning hepatocellular cancer patients undergoing preliver transplantation TACE. Quality assessment of studies was done by the validated checklist of Downs and Black. Meta-analyses were performed to evaluate the incidence of all hepatic artery complications, hepatic artery thrombosis, and biliary tract complications, using binary random-effect models. RESULTS: Fourteen retrospective studies, representing 1122 TACE patients, met the inclusion criteria. Postoperative hepatic artery complications consisted of hepatic artery thrombosis, stenosis, and (pseudo)-aneurysms. Preliver transplantation TACE was significantly associated with occurrence of posttransplant hepatic artery complications (odds ratio, 1.57; 95% confidence interval, 1.09-2.26; P = 0.02). No significant association between neoadjuvant TACE and hepatic artery thrombosis alone or biliary tract complications was found. CONCLUSIONS: Patients treated with TACE before liver transplantation may be at increased risk for development of hepatic artery complications after liver transplantation.

Trial design and endpoints in clinical transplant research.

The number of clinical trials in solid organ transplantation is progressively increasing year on year, but the quality of design and reporting still varies considerably. The constraints on organ availability, improving short-term outcomes, ethics and timescales involved in organ transplantation present unique challenges for trials in this field. An understanding of the methodology and potential pitfalls in clinical research is essential both to interpret trial results and to design robust studies. This review summarizes the scope and quality of reporting in existing transplant clinical trials and details aspects of clinical trial methodology with particular relevance to transplantation. We highlight initiatives designed to improve the quality of this process to ensure that the results of clinical trials are robust, well reported and of use in everyday clinical practice.

Does belatacept improve outcomes for kidney transplant recipients? A systematic review.

BACKGROUND: Belatacept was intended to provide better outcomes for kidney transplant (KT) recipients by allowing minimization/withdrawal of calcineurin inhibitors (CNI) and steroids. METHODS: We searched for randomized controlled trials (RCTs) in adult KT comparing belatacept with CNIs. Methodological quality was assessed. Meta-analyses were performed to calculate odds ratios (OR) and mean differences (MD). RESULTS: Six RCTs were included. Pooled analyses found no differences for acute rejection at any time point. Renal function [Calculated glomerular filtration rate (cGFR)] was better with belatacept at 12 and 24 months (MD = 11.7 and 13.7 ml/min/1.73 m(2) ). New onset diabetes after transplantation was lower with belatacept at 12 months (OR = 0.43). Systolic and diastolic blood pressures were lower at 12 months (MD -7.2 and -3.1 mmHg) as were triglycerides at 12 and 24 months (MD = -32.9 and -41.7 mg/dl). Total and low-density lipoprotein cholesterol were lower with belatacept at 24 months (MD = -19.8 and -10.6 mg/dl). There were no differences for other outcomes. CONCLUSION: Limited available data suggest a potential benefit for belatacept by reducing the risk of CNI toxicity, especially renal function, without evidence of increased acute rejection. There were no safety issues apart from a possible risk of post-transplant lymphoproliferative disorder in Epstein-barr virus-seronegative recipients. Further studies are required to confirm this benefit.

Compliance to the CONSORT statement of randomized controlled trials in solid organ transplantation: a 3-year overview.

The Consolidated Standards of Reporting Trials (CONSORT) statement was developed to improve the reporting quality of randomized controlled trials (RCTs). Our primary aim was to assess to what extent reports of RCTs in solid organ transplantation adhere to the 2010 CONSORT statement. Secondly, we investigated the relationship between CONSORT adherence, methodological quality and some other factors. We included 290 RCTs that were published between 2007 and 2009. We examined to what extent trial reports complied with 30 items of the CONSORT statement. Methodological quality was evaluated using the Jadad scale plus allocation concealment and whether data analysis was by randomized group (intention to treat). On average, trial reports addressed 47% of the CONSORT items. Forty-three per cent of RCTs was considered to be of good quality according to Jadad scale, and the items allocation concealment and data analysis were satisfied in approximately one-third of trials. Good quality RCTs reported on more CONSORT items than poor quality trials. The methodological quality and adherence to the CONSORT statement of RCTs published in journals that endorse the CONSORT statement was superior to those in journals without CONSORT endorsement. Overall compliance with the CONSORT statement and the methodological quality of RCTs in organ transplantation remains unsatisfactory.

Do wound complications or lymphoceles occur more often in solid organ transplant recipients on mTOR inhibitors? A systematic review of randomized controlled trials.

mTOR inhibitors have been associated with wound complications and lymphoceles. We systematically reviewed randomized controlled trials (RCTs) to compare these outcomes for solid organ transplant recipients. Relevant medical databases were searched to identify RCTs in solid organ transplantation comparing mTOR inhibitors with an alternative therapy reporting on wound complications and/or lymphoceles. Methodological quality of RCTs was assessed. Pooled analyses were performed to calculate odds ratios (OR) and 95% confidence intervals (CI). Thirty-seven RCTs in kidney, heart, simultaneous pancreas-kidney and liver transplantation were included. Pooled analyses showed a higher incidence of wound complications (OR 1.77, CI 1.31-2.37) and lymphoceles (OR 2.07, CI 1.62-2.65) for kidney transplant recipients on mTOR inhibitors together with calcineurin inhibitors (CNIs). There was also a higher incidence of wound complications (OR 3.00, CI 1.61-5.59) and lymphoceles (OR 2.13, CI 1.57-2.90) for kidney transplant recipients on mTOR inhibitors together with antimetabolites. Heart transplant patients receiving mTOR inhibitors together with CNIs also reported more wound complications (OR 1.82, CI 1.15-2.87). We found a higher incidence of wound complications and lymphoceles after kidney transplantation and a higher incidence of wound complications after heart transplantation for immunosuppressive regimens that included mTOR inhibitors from the time of transplantation.

The quality of reporting of randomized controlled trials in solid organ transplantation.

Randomized controlled trials (RCTs) of interventions provide the highest level of evidence about efficacy but their value either alone or within a meta-analysis is dependent on its methodological quality. For this reason recent RCTs in organ transplantation were assessed for quality. RCTs published between 2004 and 2006 (n = 332) were assessed, after excluding duplicate and nonEnglish reports. Quality was evaluated using the Jadad score plus allocation concealment and intention to treat analysis. We noted journal type, journal author instructions, funding source, sample size and number and location of study centres. Around one-third of RCTs had a Jadad score of 3 or greater (indication of a methodologically good quality trial) and the other two parameters were satisfied in just over one third. Although the majority of trials were published in speciality journals the quality of those published in general journals was superior. Commercially sponsored trials were of better quality as were multicentre trials in contrast to single centre trials. Overall quality of reporting of RCTs in organ transplantation is poor and as RCTs provide the highest level of evidence in evaluations of interventions there needs to be a concerted effort within the transplant community to improve the standards of RCTs.