scholarly journals Protocol for a pilot single-centre, parallel-arm, randomised controlled trial of dietary inulin to improve gut health in solid organ transplantation: the DIGEST study

BMJ Open ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. e049184
Author(s):  
Julian Singer ◽  
Yan Jun Li ◽  
Tracey Ying ◽  
Leyla J Aouad ◽  
David M Gracey ◽  
...  
Keyword(s):  
Controlled Trial ◽  
Solid Organ Transplantation ◽  
Gastrointestinal Symptoms ◽  
Solid Organ ◽  
Transplant Recipients ◽  
Gut Health ◽  
Kidney Transplant Recipients ◽  
Single Centre ◽  
Post Transplant ◽  
Randomised Controlled

IntroductionKidney transplantation remains the best treatment for end-stage kidney disease, however the requirement for indefinite immunosuppression increases the risk of cardiovascular disease, cancer and infection, leading to a reduction in long-term patient and graft survival. The gut microbiome is a critical determinant of health and modulates host immunity and metabolism through a number of recognised pathways, including through the production of immunomodulatory short-chain fatty acids (SCFA). Dietary supplementation with non-digestible fibre can augment the microbial production of SCFA and lead to favourable immune and metabolic outcomes, although this has yet to be shown in human kidney transplant recipients.Methods and analysisDietary inulin for gut health in solid-organ transplantation (DIGEST) is a single-centre, unblinded, pilot parallel-arm randomised controlled trial designed to assess the feasibility and adherence of dietary inulin, a naturally occurring dietary fibre, in the early post-transplant period in kidney transplant recipients. Participants will be randomised at day 28 post-transplant to a 4-week period of dietary inulin (10–20 g/day) in addition to standard care, or standard care alone, and followed-up until week 12 post-transplant.The primary outcomes of the study are: (i) the feasibility of participant recruitment, randomisation and retention; (ii) adherence to the intervention (inulin) and (iii) the tolerability of inulin determined by changes in gastrointestinal symptoms as scored on the Gastrointestinal Symptom Rating Scale.Secondary outcomes include: (1) glycaemic variability determined by continuous glucose monitoring; (2) abundance of SCFA-producing microbiota, as determined by 16s rRNA sequencing of the faecal metagenome; (3) serum SCFA concentrations; (4) peripheral blood immune cell populations; (5) recipient inflammatory and metabolic profiles and (6) the incidence of biopsy-proven acute rejection and kidney function determined by estimated glomerular filtration rate.Ethics and disseminationAll study visits, clinical and laboratory assessments will be integrated into usual post-transplant care, creating no additional healthcare encounters or procedures. The risks associated with this study are minor. Inulin has been shown to be well tolerated across a variety of cohorts, with the occurrence of short-term adverse gastrointestinal symptoms self-limiting. However, with gastrointestinal adverse events common following kidney transplantation, the tolerability of inulin in this cohort remains unknown. The results of DIGEST will be published in peer-reviewed journals and presented at academic conferences. This study has been approved by the Sydney Local Health District’s Ethics Committee (Royal Prince Alfred Hospital Zone).Trial registration numberACTRN12620000623998.

scholarly journals PREBIOTIC: A Study Protocol of a Randomised Controlled Trial to Assess Prebiotic Supplementation in Kidney Transplant Recipients for Preventing Infections and Gastrointestinal Upset: A Feasibility Study

2021 ◽  
Author(s):  
Samuel Chan ◽  
Carmel M Hawley ◽  
Elaine M Pascoe ◽  
Christopher Cao ◽  
Katrina L Campbell ◽  
...  
Keyword(s):  
Randomised Controlled Trial ◽  
Kidney Transplant ◽  
Controlled Trial ◽  
Gastrointestinal Symptoms ◽  
Trial Registration ◽  
Feasibility Trial ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Double Blind ◽  
Randomised Controlled

Abstract BackgroundModulating the microbiota in the large intestine of kidney transplant recipients through prebiotic supplementation may prevent infectious complications from occurring. To date, there have been no interventional trials which have investigated this novel treatment in kidney transplantation. The aim of PREBIOTIC is to assess the feasibility of performing a randomised controlled trial of prebiotics in reducing infections and gastrointestinal symptoms in kidney transplant recipients.MethodsSixty kidney transplant patients will be recruited to a double-blind, placebo-controlled, randomised feasibility trial. Patients will be provided with prebiotic therapy or placebo for four to six weeks. Outcomes will include recruitment, adherence, tolerance, retention, laboratory parameters (including serum indoxyl sulphate, ρ-cresyl sulphate and stool collection), patients’ self-assessed quality of life, gastrointestinal symptoms and clinical outcomes.DiscussionThis trial will assess the feasibility of prebiotic supplementation in kidney transplant recipients. Prebiotics may not only alter the gut microbiota and their inherent metabolism and production of uraemic toxins, but may also prevent infections from occurring in kidney transplant recipients.Trial RegistrationAustralian New Zealand Clinical Trials Registry number ACTRN12618001057279p. The date of registration was 25th June 2018, https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=375370&isReview=true.

scholarly journals Immunosuppression reduction when administering a booster dose of the BNT162b2 mRNA SARS-CoV-2 vaccine in kidney transplant recipients without adequate humoral response following two vaccine doses: protocol for a randomised controlled trial (BECAME study)

BMJ Open ◽  
2021 ◽  
Vol 11 (10) ◽  
pp. e055611
Author(s):  
Dafna Yahav ◽  
Benaya Rozen-Zvi ◽  
Tiki Mashraki ◽  
Alaa Atamna ◽  
Haim Ben-Zvi ◽  
...  
Keyword(s):  
Randomised Controlled Trial ◽  
Kidney Transplant ◽  
Controlled Trial ◽  
Vaccine Dose ◽  
Ethics Committee ◽  
Inadequate Response ◽  
Solid Organ ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Randomised Controlled

IntroductionInadequate antibody response to mRNA SARS-CoV-2 vaccination has been described among kidney transplant recipients. Immunosuppression level and specifically, use of antimetabolite in the maintenance immunosuppressive regimen, are associated with inadequate response. In light of the severe consequences of COVID-19 in solid organ transplant recipients, we believe it is justified to examine new vaccination strategies in these patients.Methods and analysisBECAME is a single-centre, open-label, investigator-initiated randomised controlled, superiority trial, aiming to compare immunosuppression reduction combined with a third BNT162b2 vaccine dose versus third dose alone. The primary outcome will be seropositivity rate against SARS-CoV-2. A sample size of 154 patients was calculated for the seropositivity endpoint assuming 25% seropositivity in the control group and 50% in the intervention group. A sample of participants per arm will be also tested for T-cell response. We also plan to perform a prospective observational study, evaluating seropositivity among ~350 kidney transplant recipients consenting to receive a third vaccine dose, who are not eligible for the randomised controlled trial.Ethics and disseminationThe trial is approved by local ethics committee of Rabin Medical Center (RMC-0192-21). All participants will be required to provide written informed consent. Results of this trial will be published; trial data will be available. Protocol amendments will be submitted to the local ethics committee.Trail registration numberNCT04961229.

A systematic review of post-transplant lymphoproliferative disorder after lung transplant.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e19046-e19046
Author(s):  
Mobeen Zaka Haider ◽  
Zarlakhta Zamani ◽  
Fnu Kiran ◽  
Hasan Mehmood Mirza ◽  
Muhammad Taqi ◽  
...  
Keyword(s):  
Lymphoproliferative Disorder ◽  
Lung Transplant ◽  
Late Onset ◽  
Adult Population ◽  
Solid Organ Transplantation ◽  
Chemotherapeutic Agents ◽  
Solid Organ ◽  
Transplant Recipients ◽  
Post Transplant ◽  
Lung Transplant Recipients

e19046 Background: Post-transplant lymphoproliferative disorder (PTLD) is a serious complication after solid organ transplantation. This study aims to explore the association of PTLD diagnosed after lung transplant with infectious agents and immunosuppression regimen, explore types of PTLD, and their outcome. Methods: Following the PRISMA guideline, we searched the literature on PubMed, Cochrane, Embase, and clinicaltrials.gov. 1741 articles were screened and included five studies. Results: We analyzed data from five studies, n=13,643 transplant recipients with n=287 (2.10%) developed PTLD. Four studies showed that 32/63 (51%) PTLD patients were male and 31 (49%) were female. Three studies reported 53/55 (96.4%) patients were EBV positive at PTLD diagnosis. Courtwright. et al, reported that 217/224 (97%) PTLD was associated with either EBV positive donor or recipient. Four studies showed that the monomorphic B cell type 48/63 (76%) was the most common histological type of PTLD diagnosed with DLBCL the most common subtype 31/48 (64.6%). Data from 3 studies showed that the onset of PTLD following lung transplant varies with a median duration of 18.3 months (45 days to 20.2 years). Three studies showed that 26/55 (47.3%) patients had early-onset (≤ 1 yr of Tx) and 29/55 (52.7%) patients had late-onset PTLD (> 1 yr of Tx). Management of PTLD included a reduction in immunosuppression including corticosteroids, CNI, purine synthesis inhibitors, Rituximab, and chemotherapeutic agents. Three studies showed a mortality rate of 30/45 (66.7%) and 13/30 (43.3%) deaths were PTLD related. Conclusions: Our review concludes that PTLD is a serious complication, only 2% of lung transplant recipients developed PTLD. EBV seropositivity is the most factor associated with PTLD diagnosis. Monomorphic PTLD was reported as the most common type in the adult population and no association between gender and PTLD was found. The analysis shows that there is a slightly lower incidence of early (≤ 1 yr of Tx) than late-onset (> 1 yr of Tx) PTLD. Table 1 PTLD after a Lung transplant in adults - a review. [Table: see text]

Risk Factors for Premature Coronary Heart Disease after Successful Liver Transplantation in Adults

1996 ◽  
Vol 6 (4) ◽  
pp. 178-187
Author(s):  
Susan L Smith
Keyword(s):  
Risk Factors ◽  
Coronary Heart Disease ◽  
Liver Transplantation ◽  
Heart Disease ◽  
Solid Organ Transplantation ◽  
Solid Organ ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Pharmacological Agents ◽  
Premature Coronary Heart Disease

As solid-organ transplantation has evolved into a highly effective treatment for end-stage organ disease, the long-term health implications of chronic exposure of recipients to immunosuppressants and other pharmacological agents are becoming more apparent. Coronary heart disease has long been known to plague kidney transplant recipients and more recently has been found to affect heart transplant recipients disproportionately. Coronary heart disease after liver transplantation, however, is less well known. The purpose of this study was to examine risk factors for premature coronary heart disease in asymptomatic adult recipients of liver transplants. Nutrition-related risk factors for coronary heart disease (obesity and hyperlipidemia) were measured in 29 patients before and after liver transplantation. Changes with respect to primary immunosuppression protocol (cyclosporine plus corticosteroid vs tacrolimus plus corticosteroid) were compared. Risk factors that had not been present before transplantation were apparent in both groups by 6 months after transplantation. Although obesity and hyperlipidemia were not found to be independent risk factors for coronary heart disease, they were clinically important when considered in combination. Cyclosporine was associated with significantly higher serum lipid concentrations than was tacrolimus.

Solid Organ Transplantation in HIV-Infected Individuals

2017 ◽  
Author(s):  
Eurides Lopes ◽  
Jennifer Husson
Keyword(s):  
Organ Transplantation ◽  
Opportunistic Infections ◽  
Solid Organ Transplantation ◽  
Team Approach ◽  
Solid Organ ◽  
Hiv Disease ◽  
Transplant Recipients ◽  
Post Transplant ◽  
Liver And Kidney ◽  
Infectious Disease Specialists

End-organ disease has become a major cause of morbidity and mortality in HIV-infected patients due to increased life expectancy, increasing the demand for organ transplantation in these patients. The care of HIV-infected transplant recipients warrants a multidisciplinary team approach, including the transplant team, pharmacists, infectious disease specialists, nurses, and patients and their families. The immunosuppression of HIV-infected recipients post-transplant does not appear to further advance HIV disease. The post-transplant risk for HIV-infected recipients of opportunistic infections does not appear to be increased by immunosuppression. However, the overall rate of infections is high, and it is even higher in hepatitis C virus (HCV) co-infected transplant recipients. HIV/HCV co-infected recipients have worse outcomes compared to both liver and kidney HIV-infected recipients.

scholarly journals Randomised controlled trial of a video intervention and behaviour contract to improve medication adherence after renal transplantation: the VECTOR study protocol

BMJ Open ◽  
2019 ◽  
Vol 9 (3) ◽  
pp. e025495 ◽  
Author(s):  
Holly Mansell ◽  
Nicola Rosaasen ◽  
Patricia West-Thielke ◽  
Jenny Wichart ◽  
Christopher Daley ◽  
...  
Keyword(s):  
Kidney Transplantation ◽  
Medication Adherence ◽  
Randomised Controlled Trial ◽  
Usual Care ◽  
Self Efficacy ◽  
Controlled Trial ◽  
Transplant Recipients ◽  
Post Transplant ◽  
Video Intervention ◽  
Randomised Controlled

IntroductionNon-adherence after kidney transplantation contributes to increased rejections, hospitalisations and healthcare expenditures. Although effective adherence interventions are sorely needed, increasing education and support to transplant recipients demands greater use of care providers’ time and resources in a healthcare system that is stretched. The objective of this clinical trial is to determine the effectiveness of an electronically delivered video series and adherence behaviour contract on improving medication adherence to immunosuppressant medications.Methods and analysisA multicentre, parallel arm, randomised controlled trial will be conducted with four sites across North America (Saskatoon, Calgary, Halifax, Chicago). Adult patients will be randomised (1:1) to either the intervention (ie, home-based video education +behaviour contract plus usual care) or usual care alone. De novo transplant recipients will be enrolled prior to their hospital discharge and will be provided with electronic access to the video intervention (immediately) and adherence contract (1 month post-transplant). Follow-up electronic surveys will be provided at 3 and 12 months postenrolment. The primary outcome will be adherence at 12 months post-transplant, as measured by self-report Basel Assessment of Adherence to Immunosuppressive medications and immunosuppressant levels. Secondary outcomes include the difference in knowledge score between the intervention and control in groups (measured by the Kidney Transplant Understanding Tool); differences in self-efficacy (Generalised Self-efficacy Scale), Beliefs of Medicine Questionnaire (BMQ), quality of life (Short Form-12), patient satisfaction and cost utilisation. The study aims to recruit at least 200 participants across participating sites.Ethics and disseminationEthical approval was obtained from the University of Saskatchewan Behavioural Ethics Committee (Beh 18–63), and all patients provide informed consent prior to participating. This educational intervention aims to improve information retention and self-efficacy, leading to improved medication adherence after kidney transplantation, at low cost, with little impact to existing healthcare personnel. If proven beneficial, delivery can be easily implemented into standard of care.Trial registration numberNCT03540121; Pre-results.

scholarly journals 583. Successful prevention of Strongyloides reactivation in liver transplant recipients with individualized screening and treatment: 10 year experience at a large transplant center in New York City

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S356-S356
Author(s):  
Farah Rahman ◽  
Sarah Taimur ◽  
Melissa R Gitman ◽  
Dallas Dunn ◽  
Emily Baneman ◽  
...  
Keyword(s):  
Risk Factors ◽  
Liver Transplant ◽  
Solid Organ Transplantation ◽  
Study Cohort ◽  
High Morbidity ◽  
Solid Organ ◽  
Transplant Recipients ◽  
Positive Serology ◽  
Post Transplant ◽  
Serologic Testing

Abstract Background Strongyloides stercoralis is an intestinal nematode that can establish chronic, asymptomatic infection in human hosts. Following solid organ transplantation, subclinical infection may progress to hyperinfection syndrome, which is associated with high morbidity and mortality. However, the optimal approach for screening and treatment of strongyloidiasis in liver transplant candidates in non-endemic areas is unknown. Methods We performed a retrospective chart review of all liver transplant (LT) recipients from 2010–2019. All patients were evaluated by an infectious diseases physician prior to transplant, and screening for Strongyloides exposure (with Strongyloides IgG antibody) was typically limited to those with risk factors for strongyloidiasis. Only patients with positive serologic testing or other evidence of strongyloidiasis were treated with ivermectin. Results One thousand and seventy-two LT cases (including 15 retransplants) were reviewed. Serologic testing was perfomed in 664 cases, of which 36 (5.4% of those tested, 3.4% of total) were positive. Of the 36 cases with positive serologic testing, 31 had identifiable risk factors including birth place, travel or eosinophilia. Eosinophilia (defined as peripheral eosinophila greater than 5%) was noted in 3 of the 36 recipients who had positive serology. Of the total 36 cases with positive serology, 18 were treated both pre- and post-transplant, 7 were treated only pre-transplant and 9 were treated only post-transplant. One patient died prior to initiating treatment, and one did not have documented treatment. One patient with negative serologic testing was empirically treated due to persistent eosinophilia. There was one case of Strongyloides hyperinfection due to likely donor-derived infection. There were no cases of Strongyloides reactivation in the study cohort. Conclusion This study demonstrates that an individualized screening and treatment protocol can effectively prevent Strongyloides reactivation in LT recipients. Given the high mortality rate of Strongyloides hyperinfection, especially in solid organ transplant recipients, a methodical assessment of epidemiologic risk is essential for appropriate risk stratification and management of Strongyloides in LT candidates. Disclosures All Authors: No reported disclosures

P1624TORQUE TENO VIRUS FOR RISK STRATIFICATION OF GRAFT REJECTION AND INFECTION IN KIDNEY TRANSPLANT RECIPIENTS - A PROSPECTIVE OBSERVATIONAL TRIAL

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Konstantin Doberer ◽  
Georg A Böhmig ◽  
Elisabeth Puchhammer-Stöckl ◽  
Gregor Bond
Keyword(s):  
Risk Stratification ◽  
Kidney Transplant ◽  
Graft Rejection ◽  
First Year ◽  
Solid Organ ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Observational Trial ◽  
Post Transplant ◽  
Interventional Trial

Abstract Background and Aims The non-pathogenic and ubiquitous Torque Teno virus (TTV) is associated with immunosuppression in solid organ transplant recipients. Studies in kidney transplant patients proposed TTV quantification for risk stratification of graft rejection and infection. This prospective observational trial was designed to assess the potential of TTV load for risk prediction of both, infection and rejection in the first year after transplantation. The objective of this trial was to provide TTV cut-off level to define an optimal TTV range as a basis for a randomised controlled interventional trial to test the efficacy of TTV-guided immunosuppression. Method Within this trial (DRKS00012335) all 386 adult (≥18 years of age) consecutive kidney graft recipients transplanted at the Medical University Vienna, Austria, between January 1st 2016 and June 31st 2018. were subjected to longitudinal per protocol TTV monitoring. In total 3265 TTV measurements were taken and 71 biopsy proven graft rejections (defined by BANFF classification) and 472 clinically relevant infections were documented in the first year post-transplant. After reaching steady state at the end of post-transplant month 3, peripheral TTV plasma load was analyzed in the context of subsequent rejection and infection by rt-PCR. Results Patients with allograft rejection had lower levels of TTV compared to patients without rejection (median 3.5x106 c/mL, IQR 1.7x105-1.3x108 c/ml vs. median 2.5x108 c/mL, IQR 5.8x106-9.3x108 c/mL; P = .028) in subsequent biopsies. TTV load in individuals experiencing an infectious event in the subsequent observation period was higher compared to patients without infection (median 3.9x108 c/mL, IQR 7.9x106-3.3x109 c/mL vs. median 2.6x107 c/mL, IQR 1.3x106-9.2x108 c/mL; P < .001). Of note, TTV was quantified several weeks before rejection diagnosis and infection onset. Each log increase in TTV load decreased the odds for rejection by 22% (OR 0.78, 95% CI 0.62-0.97; P = .027) and increased the odds for infection by 11% (OR 1.11, 95% CI 1.06-1.15; P < .001). The association of TTV and infection and rejection, respectively was not altered by confounding or effect modification. A TTV load between 106 and 108 copies/mL was defined as optimal range to minimize the risk for rejection and infection. Conclusion These data support the initiation of an interventional trial assessing the efficacy of TTV-guided immunosuppression to reduce infection and graft rejection in kidney transplant recipients.

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