Clinical Research Directory

A Trial to Treat Polyomavirus Infections (BKPyV) in Kidney and Simultaneous Kidney Pancreas Transplant Recipients

BEAT-BK will see the effect of immunosuppression reduction/modification with and without IVIG on BKPyV infection, allograft function, allograft loss, acute transplant rejection, immunosuppression load and death in kidney and simultaneous kidney pancreas transplant recipients with polyomavirus infections (BKPyV).

Prevalence of BK Viremia in Simultaneous Liver-Kidney Transplant

The human BK polyomavirus is a significant risk factor for renal transplant dysfunction and allograft loss. The prevalence of BK viremia (BKV) following kidney transplantation is estimated to be 10-20%.

Effectiveness of an Immune-guided Cytomegalovirus Infection Preventive Strategy Compared to a Universal Prophylactic Strategy in Renal Transplant Patients

Cytomegalovirus (CMV) establishes a chronic infection in 60% of the general population. In renal transplant recipients, it is responsible for morbidities occurring mainly in the first 6 months after transplantation. These include viral reactivations linked to immunosuppressive treatment inhibiting the anti-CMV T lymphocyte response. CMV infection, a sign of uncontrolled viral replication, is defined by the detection of viral DNA in the peripheral blood (DNAemia). CMV disease is defined as the association of an infection and symptoms attributable to the virus. In transplant recipients carrying the virus before transplantation (positive serology: CMV+), two infection prevention strategies are recommended: either close monitoring of DNAemia with antiviral treatment in the event of positive detection (pre-emptive strategy), or antiviral treatment for the first 3 months following the transplant (prophylactic strategy). Both strategies result in the occurrence of CMV infection in 15 to 20% of patients within the first 6 months, with the majority of events occurring between 3 and 6 months. Numerous studies show that the evaluation of the anti-CMV T lymphocyte response, either before (D0) or early after transplantation (D15), or when antiviral prophylaxis is stopped, allows the identification of patients at risk of CMV infection. No study has yet demonstrated the contribution of such an evaluation in a preventive strategy.

Prediction and Prevention of Bloodstream Infections After Kidney Transplantation

Background: Kidney transplant (KTx) recipients receive life-long immunosuppression, which increases the risk of severe infections. Bloodstream infections (BSI) are common after transplantation and are associated with high mortality and morbidity. Prophylactic antibiotic treatment of all KTx recipients does not provide overall benefit, but a personalized strategy of prophylactic treatment of KTx recipients at high risk of BSI with targeted antibiotics has not been assessed. Primary aim: To determine if prophylactic pivmecillinam in high-risk KTx recipients decreases the incidence of Enterobacterales BSI in the first 1-6 months post-transplantation. Secondary aim: To assess if prophylactic pivmecillinam reduces all-cause mortality, hospital admissions, graft loss, changes in the gut and urine resistome and microbiome, and increases quality of life in high-risk KTx recipients. Design and target group: Multi-center double-blinded randomized controlled trial of 150 KTx recipients at high risk of BSI who will be randomized 1:1 to either pivmecillinam 400 mg once daily or placebo from months 1-6 post-transplantation. KTx recipients will be included from Rigshospitalet, Aarhus University Hospital and Odense University Hospital. 60 participants in each study arm will provide urine and stool samples at randomization and at the end of intervention for metagenomic sequencing of the bacterial microbiome and resistome. Perspectives: This trial will provide evidence necessary to assess if KTx recipients at high risk of BSI benefit from targeted prophylactic antibiotics and address a critical knowledge gap of how to reduce mortality and morbidity due to BSI after KTx. The study will also serve as proof-of-concept for a personalized approach to infection prevention in other populations at high risk of severe infections. Results from the study may easily be implemented since there is already a clinical set-up for prevention of viral infections in KTx recipients.

The Efficacy of Everolimus With Reduced-dose Tacrolimus Versus Reduced-dose Tacrolimus and Leflunomide in Treatment of BK Virus Infection in Kidney Transplantation Recipient

BK virus infection is one of the causes of renal allograft loss in the current era. Reduction of immunsuppression is the only intervention that prooved to be effective in treating of BK virus in kidney transplant recipient. However, there are evidences from retrospective and prospective studies showed that leflunomide and mTOR inhibitor such as everolimus or sirolimus have positive outcomes in treatment of BK virus in kidney tranplant recipient. The investigators conduct the RCT to compare the efficacy of leflunomide and mTOR inhibitor everolimus, in treatment of BK virus infected patients who do not respond to immunosuppression reduction.

Letermovir (Prevymis) for CMV in Kidney and Pancreas Transplant Recipients

This study is designed to assess how effective letermovir is in preventing recurrence of cytomegalovirus (CMV) infection in adult kidney or kidney/pancreas transplant recipients who are UW Health patients. Participants will be in the study for about 6 months.

Early vs Late Urinary Catheter Removal After Renal Transplantation

The purpose of this study is to compare frequency of UTI, urine leak and need for reoperation in patients after renal transplant with early or delayed Foley catheter removal. The hypothesis of the ELUCATR trial is that there is no need to keep Foley catheter longer than 24 hours after kidney transplant due to lack of significant effect on urological complications (urine leak, ureter strictures). Early removal can also reduce urinary tract infections. Main advantage of urinary catheter placement is continual diuresis monitoring and lower bladder pressure. Some hypothesize that increased pressure can disrupt ureteroneocystostomy with resultant urinary fistula. Clinical practice is to remove the catheter between 1-10 post-transplant day. Only few studies described removal of Foley catheter in the first 48 hours. There is no level 1 evidence for timing of urinary catheter removal after kidney transplantation. Urinary tract infection is a common complication after KTx occurring in about 7-80% patients. Studies suggest direct negative effect of UTI on long-term renal allograft function. There are several independent risk factors for developing UTI: female sex, diabetes and obesity. Duration of catheterization is a modifiable risk factor. Urine leak and ureter stenosis are relatively frequent surgical complications of kidney transplantation. Urine leaks occur in 2-9% of all kidney transplants. Most of them happen within 3 months after surgery. Urinary fistula contributes to mortality and graft loss. Majority of them need intervention with nephrostomy, pigtail ureteral stent or surgery. Anastomotic or ureter stenosis occurs in 3.1% of all kidney transplants and is usually resolved with open ureteroneocystostomy. Diagnosed and treated early, it does not affect patient and graft survival. There are no solid data documenting influence of the urinary bladder catheterization on fistulas, urinomas, ureter strictures and need for reoperation in this set of patients. European Best Renal Practice Guidelines recommend removal of the catheter as early as possible, however a randomized trial on timing and adverse event rates (urinary tract infection, urinary leakage) is needed.

Evolution of CMV Antiviral T-cell Immunity Over the Next Six Months Initiation of Treatment With Belatacept.

Belatacept inhibits T cell activation by blocking the costimulatory signal. In kidney transplantation, it limits the use of anticalcineurins while ensuring a satisfactory level of immunosuppression.

Immune Monitoring of Prevalent Kidney Transplant Recipients Using Torque Teno Virus: A Single-Center, Prospective Cohort Study

Kidney transplant recipients (KTRs) suffer from immunosuppression-related adverse events (iRAEs), such as infections and malignancy from chronic immunosuppression exposure but are also at risk of graft loss from rejection with under-immunosuppression. Biomarkers that predict both iRAEs and rejection and allow individualisation of immunosuppression exposure are lacking. While plasma viral DNA levels of Torque Teno Virus (TTV), a widely prevalent, non-pathogenic virus, have been shown to predict both iRAE and rejection in incident KTRs within 1 year after transplant, its role for prevalent KTRs on stable immunosuppression is unclear. The investigators hypothesise that plasma TTV levels can predict iRAEs and rejection in KTRs on stable immunosuppression and propose a pilot study to pursue three specific aims: (1) To determine the TTV levels and its relationship with clinical factors affecting the 'net state of immunosuppression' in prevalent KTRs. (2) To analyse the prognostic value of TTV levels for iRAEs and rejection in prevalent KTRs. (3) To compare the prognostic performance of TTV levels to commonly available biomarkers and composite prognostic scores. The investigators seek pursue these aims by performing a single-centre, prospective, observational cohort study of 172 KTRs on stable immunosuppression for more than 3 months. TTV levels will be measured, using the TTV R-GENE® kit, upon recruitment and when kidney allograft biopsies are performed. Subjects will be monitored for iRAEs and rejection for at least 12 months. The study will provide data on the distribution of TTV levels in a prevalent cohort of KTRs and analyse its relationship with clinical factors and important clinical outcomes. If the study indicates that TTV may be predictive of iRAEs and rejection, the investigators aim to conduct further studies including interventional studies using TTV levels to guide immunosuppression. Ultimately, the investigators aim to use TTV as a biomarker to optimise long-term immunosuppression exposure, reduce the risk of iRAEs without increase in rejection, and improve long-term outcomes for KTRs.

PRObiotics for KIdney Transplantation

The goal of this clinical trial is to assess if dietary supplememtation with OMNi-BiOTiC® 41167 reduces the risk of urinary tract infections in kidney transplant recipients. It will also assess whether it reduces the risk of graft rejection, modify immunosuppressive regimen, improves post-transplant gastrointestinal and bladder microbiome, gastrointestinal symptoms and quality of life. The main questions it aims to answer are: * Does daily intake of OMNi-BiOTiC® 41167 reduce the incidence and number of episodes of urinary tract infections? * Does daily intake of OMNi-BiOTiC® 41167 reduce the incidence and number of episodes of acute graft rejection? * Does dietary supplementation with OMNi-BiOTiC® 41167 modify gut and bladder microbiome? * Does dietary supplementation with OMNi-BiOTiC® 41167 modify tacrolimus metabolism and immunosuppressive state? * Does dietary supplementation with OMNi-BiOTiC® 41167 improves gastrointestinal symptoms and quality of life? Researchers will compare drug OMNi-BiOTiC® 41167 to a placebo (a look-alike substance that contains no drug) to see if OMNi-BiOTiC® 41167 exerts any clinically relevant beneficial effect. Participants will: * Take OMNi-BiOTiC® 41167 or a placebo every day for 6 months * Undergo clinical surveillance with seriated visit the clinics for checkups and laboratory analysis * Provide seriated urine and stool samples for microbiome analysis * Respond to seriated questionnaire on gastrointestinal symptoms and quality of life

SARS-COV-2 Infection in Kidney Transplant Recipients: a Brazilian Multicenter Study

COVID-19 is the pandemic disease caused by the SARS-CoV-2 coronavirus. It is a highly contagious viral disease, the condition of which main clinical symptoms are characterized by fever and respiratory symptoms. Evidence indicates to worse outcomes in patients with pre-existing diseases, such as diabetes, arterial hypertension, heart disease, pneumopathies, chronic kidney disease, and immunodeficiencies. Recipients of kidney transplants make prolonged use of immunosuppressive drugs to inhibit the acquired immune response, notably the activity of lymphocytes. Due to this potential to modulate the immune and inflammatory response, it is speculated that the clinical and laboratory condition of COVID-19 in these patients is atypical. Preliminary evidence suggests worse outcomes of COVID-19 in immunosuppressed patients, as carriers of cancer. However, information on kidney transplant recipients is insufficient. So far, only reports of the case are available in the literature with different clinical presentations and outcomes. The aim of this study is, therefore, to characterize the demographics, clinical and laboratory conditions, and the outcomes of COVID-19 in kidney transplant recipients in a national multicenter cohort.

Efficacy of 7 Days Versus 14 Days of Antibiotic Therapy for Acute Pyelonephritis in Kidney Transplant Recipients, a Multicentre Randomized Non-inferiority Trial.

Infections are a major cause of morbidity and mortality in solid organ transplant recipients. In kidney transplant recipients (KTR) urinary tract infection (UTI) represent 45-72% of all infections, and 30% of all hospitalizations for sepsis. Acute transplant pyelonephritis are the most common complications occurring in more than 20% of patients, mainly in the first year after transplantation. They are associated with an increased risk of acute kidney rejection and long-term kidney graft dysfunction. Gram-negative bacteria, mainly E. coli, account for more than 70% of UTI in KTR. As those infections are favoured by urinary tract modifications/defects and immunosuppression, they are often recurrent and necessitate repeated courses of antibiotics. Selective pressure due to antibiotic consumption, along with frequent hospital admissions and immunosuppression, are well known risk factors for the development of antibiotic resistant infections. Multidrug (MDR)- or extensively (XDR)- drug resistant Enterobacteriaceae including ESBL- or carbapenemase-producing organisms, are thus increasingly observed in transplant units and represent a global threat as very few new antibiotics are expected in the next decade. One main strategy to limit antimicrobial resistance is to reduce the duration of antibiotic treatment. A 7 day-course is recommended for simple acute pyelonephritis (APN) treated with fluoroquinolones or parenteral B-lactams, prolonged up to 10 or 14 days in the presence of underlying disease at risk of complications. Most KT teams treat patients between 14-21 days as recommended by American guidelines. However, the need to extend treatment duration in immunosuppressed patients is a poorly defined concept and the optimal duration of treatment for APN in KTR is not known as these patients are excluded from most studies. As there is an urgent need to reduce antibiotic consumption in this population at high risk of developing infections due to resistant pathogens, the hypothesis is that a 7 day-treatment is sufficient to cure APN with good clinical response after 48h of treatment in KTR and is as effective as 14 days.

Use of Wearables to Detect Infections in Kidney Transplant Recipients

The goal of this observational study is to develop a machine learning algorithm for early detection of infections in kidney transplant recipients using data recorded by wearable digital health technologies. The main questions it aims to answer are: 1. What are the biometric data pattern changes in impending infections? 2. What accuracy the machine learning algorithm can achieve? Participants will be given/use their own wearable device that will record biometric data. Any infection event will be recorded and an algorithm will be trained to recognize changes in biometric data preceding symptomatic infection.

Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2) Immune Kidney Transplant Study (COVID-19)

None of the vaccines approved, or in clinical trials, have so far been tested on transplanted patients. If they produce an immune response to the Spike protein of SARS-CoV-2 it is unknown how long the protective immunity will last. Not all immune responses are equal. The investigators will quantify immune cell subsets with flow and mass cytometry analyses to describe the phenotype of responding immune cells, including specific T cells. If not already established, patient human Leukocyte antigen (HLA) genotypes will be typed. In order to compare the immune responses with healthy individuals a control group of hospital employees will be included and sampled before and after vaccination according to the same time schedules as the kidney transplanted patients.