Clinical Research Directory

Bioimpedance and Multiparametric Ultrasound-Guided Fluid Management After Kidney Transplantation

After a kidney transplant, the amount of fluid in the body must be carefully balanced. Too much fluid can accumulate in the lungs, the tissues and the new kidney itself and may delay its recovery; too little fluid can also damage it. In current practice, doctors judge fluid status mainly by physical examination, body weight and urine output, which are imprecise and often late signs. Two painless bedside tests can measure fluid status more accurately: bioimpedance, which estimates excess body water through skin electrodes, and ultrasound of the lungs, the large abdominal veins and the transplanted kidney. In a previous study by our group, these tests detected fluid overload that physical examination missed. Whether using their results to guide treatment actually improves the outcome of the transplant is unknown. This trial will compare two ways of managing fluids during the first month after transplantation: one guided by these tests and a treatment algorithm, and one based on usual clinical assessment. The aim is to find out whether test-guided management improves survival, reduces the need for dialysis in the first week and leads to better kidney function at one month.

Tolerance by Engaging Antigen During Cellular Homeostasis

Anti-rejection medicines, also known as immunosuppressive drugs, are prescribed to organ transplant recipients to prevent rejection of the new organ. Long-term use of these medicines places transplant recipients at higher risk of serious infections and certain types of cancer. The purpose of this study was to determine if: * it was safe to give mesenchymal stromal cells (MSCs) to kidney transplant recipients, and * the combination of the immunosuppressive (anti-rejection) study drugs plus the MSCs could allow a kidney transplant recipient to slowly reduce and/or then completely stop all anti-rejection drugs, without rejection of their kidney (renal) allograft, a process called "immunosuppression withdrawal".

To Assess the Efficacy and Safety of Pegcetacoplan for the Prevention of Recurrent C3G or Primary IC-MPGN in Kidney Transplant Recipients

To assess the efficacy and safety of pegcetacoplan for the prevention of recurrent C3G or primary IC-MPGN in kidney transplant recipients

Microbiota Changes Related to Outcomes in Kidney Transplantation

Chronic kidney disease affects approximately 10% of the world population. End-stage renal disease (ESRD) is associated with immune dysregulation, chronic inflammation, and alteration of the gut and urinary microbiota. Kidney transplantation is the reference treatment for ESRD, but required immunosuppressive therapy further aggravates immune dysregulation and is associated with cardiovascular, metabolic and infectious complications. The gut microbiota plays a central role in modulating systemic immunity. In ESRD, microbiota composition is strongly altered. A recent study showed an association between gut dysbiosis and all-cause mortality in over 1,300 kidney transplant recipients. However, the mechanisms underlying deleterious microbiota modifications in transplant recipients remain poorly understood, particularly the respective roles of immunosuppressive treatment and renal function recovery. The MICRO-KT study hypothesizes that the programmed introduction of immunosuppressive therapy followed by partial or complete correction of ESRD after living-donor kidney transplantation induces quantitative and qualitative modifications of the fecal microbiota, and that specific microbial signatures are associated with clinical and immunological transplant outcomes. This prospective, single-center, longitudinal, interventional, single-arm cohort study will evaluate microbiota dynamics in 30 adult patients before and after living-donor kidney transplantation. Fecal samples are collected at 14 days before transplantation (before immunosuppression), the day before transplantation (after 4 days of immunosuppression), and 3 months post-transplantation. Urinary samples are collected at transplantation. Blood samples (serum, plasma, PBMCs) are collected at 3 timepoints for immunological and metabolomic analyses. The primary endpoint is to describe fecal microbiota beta-diversity dynamics (Bray-Curtis and Jaccard indices at genus level) across three timepoints. Secondary objectives evaluate associations between microbiota composition and clinical outcomes (rejection, infection, survival), immunosuppressant tolerance, drug levels, PBMC immunological profiles, metabolomic signatures, and dietary patterns.

Effect of Probiotics on Immunosuppressant Therapy in Kidney Transplant Recipients

People who receive a donor kidney must take drugs to prevent their bodies from attacking the new organ. These drugs are called immunosuppressants. Probiotics are beneficial microbes that support gut health. They are often given to reduce immunosuppressant toxicity for the gut. The goal of this clinical trial is to learn if probiotics change the levels of immunosuppressants in the blood in patients who have received a kidney transplant. The main question it aims to answer is: • Does a short-term treatment with a probiotic mixture change the circulating levels of the immunosuppressant drugs cyclosporine A, tacrolimus, sirolimus, everolimus, mycophenolic acid, mycophenolate mofetil, and prednisolone? In addition, researchers will also see if probiotics reduce systemic inflammation or ameliorate renal function. Study participants will be patients with kidney transplant. At different times, each participant will take either probiotics or look-alike capsules with no probiotics. Researchers will compare the levels of immunosuppressant in the blood when participants take the probiotics with those when they take the capsules with no microbes. Study participants will have to: * Take oral capsules containing a probiotc mixture for one month and look-alike capsules with no probiotics for another month with a one-month interval between these two treatments; * Go to the hospital every 30 days for three months for the collection of blood samples; * Collect feces specimens for microbiome analysis every 30 days for three months and bring them to the hospital.

Study to Compare the Pharmacokinetics of Tacrolimus in Stable Pediatric Allograft Recipients Converted From Prograf® to Advagraf®

Parts A \& B: Conversion of stable pediatric allograft recipients from Prograf® immunosuppression to Advagraf® immunosuppression to compare exposure and one year follow-up for safety and efficacy. Part C: Continuation of long-term follow-up and provision of ongoing study medication to subjects to whom Advagraf® is currently not available.

Drone Transport of Deceased-Donor Kidney Grafts Between Two French Hospitals Before Transplantation: a Pilot Safety Study

Cold ischemia time, the period during which a donated kidney is kept cold outside the body between its removal from the donor and its transplantation into the recipient, is one of the main modifiable factors influencing how quickly and how well a transplanted kidney starts to work and how long it lasts. In France, kidneys are usually transported between hospitals by ambulance, car, train or plane, which exposes the graft to traffic, scheduling and coordination delays. Autonomous drones could offer a fast, dedicated and predictable alternative. A human kidney was successfully transplanted after drone transport in the United States in 2019, but no transplantation after drone transport of an organ has yet been reported in Europe. The RAfALREIN study is a pilot study designed to assess the safety and feasibility of transporting deceased-donor kidneys by autonomous drone between the Centre Hospitalier Départemental Vendée in La Roche-sur-Yon (procurement site) and Nantes University Hospital (transplantation site), within a dedicated medical air corridor subject to authorisation by the French civil aviation authority. Five adult patients will receive a kidney that has been transported by drone. Apart from the mode of transport of the graft, organ procurement, preservation, transplantation, treatments and follow-up are carried out according to usual care, with no additional examination required by the study. The main outcome is the absence of delayed graft function, defined as no need for dialysis during the first week after transplantation. Cold ischemia time, transport time, temperature and vibrations during transport, transport costs, events preventing, delaying or interrupting drone missions, and adverse events up to 30 days after transplantation are also recorded. Participants are followed for 12 months after transplantation as part of routine care. Study hypothesis: transport of kidney grafts by autonomous drone between two hospitals is safe, does not impair early graft function and is operationally feasible in real conditions, thereby supporting the design of a larger multicentre study.

Noninvasive Methods to Monitor Graft Survival in Kidney Transplant Patients

The purpose of this study is to test noninvasive methods to monitor the health and condition of new kidneys in people who have received kidney transplants.

Urine Testing to Detect Kidney Transplant Rejection

The purpose of this study is to determine if analysis of urine samples for specific markers can predict transplant rejection in people who have received kidney transplants.

Proteogenomic Biomarker Panels in a Serial Blood & Urine Monitoring Study of Kidney Transplant Recipients

There is a need to develop blood and/or urine tests that will help to detect early signs of rejection in people who have had kidney transplant. Researchers will examine blood, urine, and tissue samples and try to identify genetic markers for certain conditions like rejection, response to therapy, and scarring of the kidney. By studying gene patterns, researchers hope to be able to diagnose these conditions earlier and improve kidney survival.

Associating Renal Transplantation With the ITN Signature of Tolerance

This is an observational study for people who have received a kidney transplant within the past 1 to 5 years. Researchers in this study are looking for a certain pattern of genes and cells in the blood that has been found in a group of rare transplant patients who do not need immunosuppression. The study goal is to find out how common this pattern is in transplant patients, as a first step in determining if it can be used to personalize anti-rejection drug regimens better.

Effects of Donor and Recipient Genetic Expression on Heart, Lung, Liver, or Kidney Transplant Survival

Activity of genes in donor tissues that are involved in inflammation are thought to be involved with early organ dysfunction, increased immune responses in transplant recipients, and organ rejection. The purpose of this study is to determine the relationship between genetic expression in donor and recipient tissue with transplant survival. Participants in this study will have received heart, lung, liver, or kidney transplants.

Optimization of NULOJIX® Usage As A Means of Avoiding CNI and Steroids in Renal Transplantation

The purpose of this study was to assess whether a new drug, Nulojix® (belatacept), would minimize serious long term side effects associated with anti-rejection medications while still protecting the new kidney from damage. The researchers also wanted to learn more about the safety of this treatment and long term health of the transplanted kidney.

Open-Label Phase 2 Trial of a Steroid-Free, CNI-Free, Belatacept-Based Immunosuppressive Regimen

The primary objective is to evaluate a NULOJIX® (belatacept) based regimens as a means of improving long-term graft function without increasing the risks of immunologic graft injury by avoiding both calcineurin inhibitors (CNIs) and corticosteroids.

The Impact of Intraoperative Diuretic Use on Delayed Graft Function Following Deceased Donor Renal Transplantation

Delayed graft function, defined as the need for dialysis within seven days of kidney transplantation, is a common complication affecting deceased-donor kidney transplant recipients. It is associated with prolonged hospitalization, increased healthcare costs, higher rates of acute rejection, and poorer long-term graft survival. Intraoperative diuretics are routinely administered during kidney transplant surgery to promote early urine output and protect the kidney from injury during reperfusion. The two most commonly used agents are furosemide and mannitol. Despite decades of clinical use, no prospective randomized trial has directly compared these two medications, and practice remains highly variable across centres and individual surgeons. This single-centre, prospective, randomized, surgeon-blinded pilot trial will enroll 240 deceased-donor kidney transplant recipients at London Health Sciences Centre. Participants will be randomized in a 1:1 ratio, stratified by donor type, to receive either intraoperative furosemide or intraoperative mannitol. The primary feasibility outcomes include recruitment rate. The primary clinical outcome is the incidence of delayed graft function. Secondary outcomes include serum creatinine trajectory, urine output, dialysis requirements, perioperative complications, length of stay, and one-year graft and patient survival. This pilot trial will provide feasibility data and effect-size estimates necessary to inform the design of a future definitive multicentre randomized controlled trial.

Cardiac Improvement by Eplerenone Among Patients Under Cyclosporine or Tacrolimus for Kidney Transplantation.

The main objective of this research is to evaluate the effect, for 36 weeks, of eplerenone on abnormalities observed on cardiac ultrasound in patients with kidney transplantation for at least one year, under cyclosporine or tacrolimus. The intervention group will receive the usual standard treatment coupled with eplerenone for 36 weeks from randomization, while the control group will only receive the standard treatment. The main hypothesis is that anticalcineurins (cyclosporin or tacrolimus) lead to activation of the MR of vascular smooth muscle cells, vasoconstriction and vascular inflammation, which contributes to the persistence or recurrence of heart abnormalities in these patients after the initial post-transplant phase. The administration of eplerenone could antagonize this hyperactivation, reduce the cardiovascular effects of anticalcineurins and thus ultimately improve the cardiovascular prognosis of transplant patients.

Cell Therapy for Immunomodulation in Kidney Transplantation

This study investigates treatment with recipient regulatory T cells and donor bone marrow together with tocilizumab for immunomodulation in living donor kidney transplant recipients.

Ex Vivo Normothermic Perfusion in Kidney Transplantation.

A multicenter, prospective and open-label clinical investigation to evaluate the viability, performance and safety of ex vivo normothermic perfusion in kidney transplantation from DCD and DBD donors.

Study to Evaluate the Safety and Efficacy of the GGTA1 KO Thymokidney in Patients With ESRD

The purpose of this study is to evaluate the safety and efficacy of the GGTA1 KO Thymokidney in patients with end-stage renal disease (ESRD) who are either not eligible for conventional allogeneic kidney transplantation (Group 1) or are on an Organ Procurement and Transplantation Network (OPTN) kidney transplant waitlist, but are more likely to die or go untransplanted within 5 years than receive a kidney transplant (Group 2). The study consists of xenotransplantation followed by a 24-week Post-transplant Follow-up Period (Part A) to evaluate the efficacy and safety objectives followed by a Long-term Follow-up Period (Part B) to evaluate participant survival, GGTA1 KO Thymokidney survival, and screening for zoonotic infections. Part B will continue for the lifetime of the participant or for 52 weeks following nephrectomy, if required.

APOL1 Genetic Testing Program for Living Donors

Living donor (LD) kidney transplantation is the optimal treatment for patients with end-stage kidney disease (ESKD). However, LDs take on a higher risk of future ESKD themselves. African American (AA) LDs have an even greater, 3.3-fold, risk of ESKD than white LDs post-donation. Because evidence suggests that Apolipoprotein L1 (APOL1) risk variants contribute to this greater risk, transplant nephrologists are increasingly using APOL1 testing to evaluate LD candidates of African ancestry. However, nephrologists do not consistently perform genetic counseling with LD candidates about APOL1 due to a lack of knowledge and skill in counseling about APOL1. Without proper counseling, APOL1 testing will magnify LD candidates' decisional conflict about donating, jeopardizing their informed consent. Given their elevated risk of ESRD post-donation, and AAs' widely-held cultural concerns about genetic testing, it is ethically critical to protect AA LD candidates' safety through APOL1 testing in a culturally competent manner to improve informed decisions about donating. No transplant programs have integrated APOL1 testing into LD evaluation in a culturally competent manner. Clinical "chatbots," mobile apps that use artificial intelligence to provide genetic information to patients and relieve constraints on clinicians' time, can improve informed treatment decisions and reduce decisional conflict. The chatbot "Gia," created by a medical genetics company, can be adapted to any condition. However, no chatbot on APOL1 is currently available. No counseling training programs are available for nephrologists to counsel AA LDs about APOL1 and donation in a culturally competent manner. Given the shortage of genetic counselors, increasing nephrologists' genetic literacy is critical to integrating genetic testing into practice. The objective of this study is to culturally adapt and evaluate the effectiveness of an APOL1 testing program for AA LDs at two transplant centers serving large AA LD populations (Chicago, IL, and Washington, DC). The APOL1 testing program will evaluate the effect of the culturally competent testing, chatbot, and counseling on AA LD candidates' decisional conflict about donating, preparedness for decision-making, willingness to donate, and satisfaction with informed consent. The specific aims are to: 1. Adapt Gia and transplant counseling to APOL1 for use in routine clinical practice 2. Evaluate the effectiveness of this intervention on decisional conflict, preparedness, and willingness to donate in a pre-post design 3. Evaluate the implementation of this intervention into clinical practice by using the RE-AIM framework to longitudinally evaluate nephrologist counseling practices and LDs' satisfaction with informed consent. The impact of this study will be the creation of a model for APOL1 testing of AA LDs, which can then be implemented nationally via implementation science approaches. APOL1 will serve as a model for integrating culturally competent genetic testing into transplant and other practices to improve patient informed consent.

Multiparametric MRI in a Prospective Cohort of Living Kidney Donors, Recipients, and Healthy Controls: Correlations With Markers of Renal Function, Fibrosis and Ageing

Development of renal fibrosis is the irreversible culmination of various renal diseases and independently predicts adverse outcomes. Currently renal fibrosis can only be diagnosed by performing a renal biopsy. The procedure is invasive and is limited by sampling bias. In recent years there has been a significant development in magnetic resonance imaging (MRI) based techniques. MRI can provide highly detailed anatomical images. Other MRI measures allow quantitative measurements of perfusion, oxygenation, tissue stiffness and diffusion of water molecules within tissue. The combination of several MRI techniques sensitive to different biophysical tissue properties in a single scan session is referred to as multiparametric MRI (mpMRI). Emerging evidence suggests that mpMRI could represent a method for indirect characterization of renal microstructure and extent of fibrosis. So far, studies performed in living kidney donors and recipients have been mostly cross-sectional. For mpMRI to transition to the clinical setting there is a need for validation of MRI-based measures with currently used reference methods for quantifying renal function and fibrosis. The aim of this longitudinal observational study in a cohort of living kidney donors, recipients and healthy controls is to investigate the utility of repeated mpMRI over a period of 2 years. MRI-based measures will be compared to current reference methods for quantifying renal function and fibrosis. The investigators hypothesize that there will be significant correlations between MRI-based measures, renal function determined by precise measurement of glomerular filtration rate and extent of fibrosis determined by renal biopsy. MRI-based measures are expected to be predictive of renal function decline and development of renal fibrosis. This study could provide valuable data that will be helpful in moving the field of renal mpMRI forward, with the goal of providing a novel and non-invasive method for the diagnosis of renal pathology.

Intravenous Immunoglobulins for Prevention of BKV Infection in Kidney Transplant Recipients According to BKV Genotype-specific Neutralizing Antibody Titers at the Day of Transplantation.

BK virus-associated nephropathy (BKVAN), a consequence of the strong immunosuppressive therapy given after kidney transplantation (KT), represents a growing medical problem in the KT setting. BKV replication occurs in 30-50% of recipients with progression to BKVAN in up to 10% of patients which ultimately leads to graft dysfunction and loss. Furthermore, early BKV replication after transplantation increases the risk of late acute rejection. At present, there are no BKV-specific antiviral therapies available. The current management of BKVAN relies on preemptive adaptation of immunosuppression according to viral load monitoring. However, due to its delayed nature, this empirical strategy is not always successful, and can increase the risk of donor specific antibodies, graft rejection and death. In a prospective longitudinal study, the investigators have demonstrated that the amount and kinetics of BKV genotype-specific neutralizing antibody (NAb) titers influence BKV disease severity after KT; and defined a cutoff NAb titer value of 4 log10 that allows stratification of recipients into lower and higher BKV disease risk groups prior to KT. Furthermore, our data on donor/recipient pairs provide support for the view reported by recent studies that early BKV replication in kidney transplant recipients is of donor origin. These data support the potential benefit of administering NAbs as a preventive strategy against BKV infection. The investigators and others have demonstrated the presence of high titers of BKV NAbs in commercial intravenous immunoglobulins (IVIG). The investigators further evaluated the titer of BKV NAbs in plasma samples of transplant recipients after administration of IVIG. The investigators demonstrated that all patients show an increase of NAb titers in plasma after IVIG administration. The aim of the investigators study is to investigate the efficacy of IVIG for prevention of BKV viremia after KT according to pre-transplant BKV genotype-specific NAb titers against the donor's BKV strain. The study is a multicentric prospective randomized open trial evaluating the impact of administration of IVIG for prevention of BKV viremia compared to no specific treatment in kidney transplant recipients harboring neutralizing antibody titers (NAbs) ≤ 4log10 against the BKV donor's genotype. Recipients harboring BKV NAb titer ≤ 4log10 against the BKV genotype of their matched donor and negative or non-detectable BKV load in blood at day of transplantation will be randomized to receive (experimental group) or not (control group) IVIG treatment. In the experimental group, patients will receive a single dose of IVIG at day 10+/- 4 days, day 41 +/- 7 days and day 62 +/- 7 days. The dose of IVIG is defined according the donor BKV genotype: genotype I: 0.4 g/Kg/day; genotype II and IV: 1g/kg/day. The incidence of BKV viremia (\> 4 log10 copies/mL) 6 months after transplantation will be evaluated and compared between the two groups.

Continuous Glucose Monitoring (CGM) After Kidney Transplantation

This study examines glucose levels measured by continuous glucose monitoring (CGM) in the immediate period following kidney transplantation among recipients with diabetes, without diabetes, and with pre-diabetes. The primary objective is to analyse differences in mean sensor glucose between these three groups. CGMs are applied to participants within 72 hours after kidney transplantation, with a total of 54 participants divided equally across the three groups (18 in each). Secondary objectives include assessing additional glucose profile indices, adherence to relevant guidelines, changes in HbA1c, the impact of immunosuppression and steroid dosage, and beta cell function.

Early (Postoperative Day 3) Versus Standard (Postoperative Day 6) Urethral Catheter Removal After Living Donor Kidney Transplantation

Urinary tract infection is one of the most common complications after kidney transplantation and is associated with increased morbidity, prolonged hospitalization, and impaired graft outcomes. The duration of urethral catheterization is a modifiable risk factor for catheter-associated urinary tract infection. This randomized controlled trial compares early catheter removal on postoperative day 3 with standard catheter removal on postoperative day 6 in living donor kidney transplant recipients. The primary objective is to determine whether early catheter removal reduces 30-day urinary tract infections without increasing urinary complications requiring intervention.