Clinical Research Directory

Effects of the SGLT2 Inhibitor Empagliflozin in Patients With Euvolemic and Hypervolemic Hyponatremia

Hyponatremia is the most common electrolyte derangement occurring in hospitalized patients. It is usually classified as hypovolemic, euvolemic or hypervolemic. The most common aetiology of euvolemic hyponatremia is the syndrome of inappropriate antidiuresis (SIAD). Hypervolemic hyponatremia is common in patients with congestive heart failure (CHF) (10-27%) and liver cirrhosis (up to approximately 50%). In SIAD, the regulation of arginine vasopressin (AVP) secretion is impaired which leads to free water retention. In CHF and liver cirrhosis, the effective arterial blood volume is decreased leading to non-osmotic baroreceptor mediated AVP release and consecutive free water retention. Current treatments of euvolemic and hypervolemic hyponatremia, including the most used treatment fluid restriction, are of limited efficacy. Sodium-Glucose-Co-Transporter 2 (SGLT2) inhibitors reduce glucose reabsorption in the proximal tubule, resulting in glucosuria and consecutive osmotic diuresis. A placebo-controlled randomized trial of our group has shown that a short-term, i.e. a 4-days administration of the SGLT2 inhibitor empagliflozin (Jardiance)® in addition to fluid restriction was effective in increasing the serum sodium concentration in 87 patients with SIAD-induced hyponatremia. The effect of empagliflozin (Jardiance)® without additional fluid restriction is however not yet known. Large randomized controlled trials have shown that SGLT2 inhibitors reduced hospitalization for heart failure in patients with, and more recently without type 2 diabetes. No studies have investigated the effect of SGLT2 inhibitors in hypervolemic hyponatremia. To evaluate the effect of empagliflozin (Jardiance)® in eu- and hypervolemic hyponatremia, a randomized placebo-controlled study is needed.

The Effect of Daratumumab in Patients With Monoclonal Gammopathy of Renal Significance (MGRS) in Finland

The goal of this clinical trial is to learn if drug daratumumab works to treat kidney diseases other than AL-amyloidosis that fall under the category of monoclonal gammopathy of renal significance (MGRS). The main questions it aims to answer are: Does daratumumab have an effect on the patients' renal function or the amount of proteinuria? Does daratumumab have an effect on the hematological endpoints evaluated by minimal residual disease (MRD) and the difference between involved and uninvolved free light chain (dFLC)? Also changes in quality of life (according to EORTC QLQ-C30) and mechanism of complement system activation are evaluated. The number of patiets with partial or very good partial hematological remission and the number of patients with adverse events related to daratumumab are also recorded.

Tenofovir Exposures in Advanced Kidney Disease Study

Phamacokinetic study to evaluate tenofovir, emtricitabine and tenofovir alafenamide exposures in people with HIV who have chronic kidney disease stage 4 (estimated glomerular filtration rate \[eGFR\] 15-29 mL/min/1.73m2) or stage 3 b (eGFR 30-44 mL/min/1.73m).

Study of the Effect of Haemodialysis on the Pharmacokinetics, Safety, and Tolerability of Balcinrenone/Dapagliflozin

The purpose of this study is to investigate the effect of HD on single oral dose PK, safety, and tolerability of balcinrenone/dapagliflozin to male and female participants with kidney failure on intermittent HD.

Hypothermic Machine Perfusion With Omnisol of Deceased Donor Kidneys Prior to Transplantation

Insufficient availability of organs from brain dead (DBD) and living donors has necessitated increased use of less than optimal organs from donation after cardiac death (DCD) or from extended criteria donors. Preservation of DCD organs using the current clinically applied preservation solutions is associated with up to 73% incidence of delayed graft function, highlighting the need for new preservation solutions designed to improve early graft function. Omnisol is expected to result in equivalent or improved kidney preservation as compared to currently marketed organ preservation solutions used for HMP.

Comparing Hepatitis B Vaccination Schedules in Patients on Hemodialysis

People with kidney failure who are on dialysis have a weaker immune response to the hepatitis B vaccine than healthy people. Even after vaccination, many dialysis patients do not develop enough protection against hepatitis B infection. Doctors do not agree on whether giving 3 doses or 4 doses of the vaccine works better for these patients. This study will compare two vaccination schedules using a stronger (double) dose of the hepatitis B vaccine in people on maintenance hemodialysis: Group 1 will receive 3 doses of the vaccine, given at the start of the study, 1 month later, and 6 months later. Group 2 will receive 4 doses of the vaccine, given at the start of the study, 1 month later, 2 months later, and 6 months later. One month after finishing their vaccine schedule, participants will have a blood test to check their antibody levels against hepatitis B. A blood level of 10 mIU/mL or higher will be considered evidence of protection (called seroprotection). The study will compare how many people in each group reach this protective level. The goal of this study is to find out which vaccination schedule (3 doses or 4 doses) gives better protection against hepatitis B in people on dialysis. The results may help doctors choose more effective vaccination strategies for dialysis patients in the future.

Comprehensive Kidney Function Assessment and Early Warning in Older Adults

This completed observational cohort study evaluates a comprehensive set of clinical and molecular markers of kidney function in two established cohorts of Chinese adults aged 60 years or older. The study assesses markers reflecting glomerular filtration, kidney tubular transport, and kidney endocrine function and evaluates their associations with kidney failure, cardiovascular and cerebrovascular events, and all-cause mortality. It also compares approaches to estimating glomerular filtration rate and develops and internally validates an early-warning model for kidney function decline. Existing baseline and follow-up data and stored serum and urine specimens are used. No intervention or additional study-specific clinical procedure is administered.

Tolerance Through Mixed Chimerism (Sip-Tego)

This is an open-label, single-institution study to assess the safety and the efficacy of the Sip-Tego regimen for the induction of donor-specific immunologic unresponsiveness to a renal allograft. The investigators propose to treat 6 adult subjects in end-stage renal disease (ESRD) who do not demonstrate evidence of prior sensitization.

Does Incremental Initiation of Haemodialysis Preserve Native Kidney Function?

Patients who start haemodialysis usually retain some natural kidney function for months or years after starting dialysis. Even a small amount of this natural kidney function can be helpful in reducing the need for dietary and fluid restriction. There is also good evidence that retaining a small amount of natural kidney function may provide a survival benefit for patients on dialysis. Most patients who commence haemodialysis start three times per week for 3.5-4 hours per session, irrespective of the amount of natural kidney function they may have. An alternative approach used in some kidney units is to take account of the natural kidney function in prescribing the amount of dialysis. This may allow patients to start treatment needing to spend less time on dialysis or even to start just twice weekly. The amount of dialysis can be adjusted over time as natural kidney function declines. This is called "incremental haemodialysis". Both of these approaches are considered to be standard care although it is not known which approach is more beneficial to patients. There are some suggestions that the frequency of dialysis may influence the rate of decline of natural kidney function but this need to be tested in a large randomised study. To inform the design of such a study, a smaller scale feasibility study is required. We intend to randomise fifty new starters on haemodialysis with adequate natural kidney function into two groups - a group who will have dialysis prescribed in the standard fashion - three times weekly for 3.5-4 hours per session or a group who will have an incremental start beginning with twice weekly treatment. We will investigate how many patients have sufficient natural kidney function to be eligible, whether patients are willing to participate and continue in the study, compare the rate of loss of kidney function between groups, and ascertain whether this individualised dialysis approach is less intrusive to patients. The results will be used to design a larger definitive study.

DAPAgliflozin for Renal Protection in Heart Transplant Recipients

Kidney failure is common in heart transplant recipients and is a major cause of morbidity and mortality. Sodium-glucose transporter 2 (SGLT2) inhibitors were developed as antidiabetics but were subsequently shown to reduce the incidence of adverse cardiovascular outcomes and protect renal function in non-diabetics as well as diabetics. However, SGLT2 inhibitors have not been tested in clinical trials in heart transplant recipients. The DAPARHT trial is designed to assess the effect of the SGLT2 inhibitor dapagliflozin to prevent deteriorating renal function in heart transplant recipients. Secondary objectives are to assess the impact of treatment on i) weight, ii) glucose homeostasis, iii) proteinuria, iv) the number of rejections, and (v) safety and tolerability. As exploratory outcomes, the investigators will assess the effect of treatment on renal outcomes, clinical events (death, myocardial infarction, cerebral stroke, cancer, and end-stage renal disease), cardiac function, quality of life, and new-onset diabetes.

Epidemiology of Complications After Solid Organ Transplantation - EpCOT Study

Cancer remains a major cause of morbidity and mortality post solid organ transplantation. While mortality from the other leading causes of death post-transplantation (e.g. cardiovascular disease and infection) is declining, mortality from cancer post-transplantation is increasing (1). This is due to both general and transplant-specific risk factors that combine to increase risk for cancer compared to the general population. However, there is a shortage of research exploring cancer epidemiology post solid organ transplantation in the UK. This is essential to guide clinicians and for counseling patients regarding expectations and outcomes after developing cancer post-transplantation. This is especially important as the aetiology, pathophysiology and outcomes of cancer post-transplantation may differ from the general population. Available data registries in the UK separately contain valuable cancer and transplant-specific data that can be combined to explore cancer epidemiology post-transplantation more comprehensively, which can be directly translated into patient benefit by utilizing transplant-specific data (rather than translating from general population or non-UK patient demographics). The purpose of this project is to combine existing data resources to link up the complete patient journey for solid organ transplant recipients and focus on the entire spectrum of cancer from incidence to mortality. In addition, we can use this linked dataset to explore many non-cancer related complications after solid organ transplantation. This will help us better understand the complete burden of disease after transplantation (which may be competing risks for development of cancer) and help improve delivery of effective post-transplant care for UK solid organ transplant patients.

STarting incrEmental Prescription of Peritoneal Dialysis

Kidney failure is fatal without dialysis. Peritoneal dialysis (PD) completed at home offers greater flexibility and autonomy for patients . However, PD is often prescribed for 24 hours/day, 7 days/week for every patient starting dialysis. This practice is not evidence-informed, may be unnecessary and potentially harmful. The STEP-PD trial aims to determine the optimal approach to commencing patients on PD through starting at low dose PD and incrementing over time.

Genetic Causes of FSGS, Nephrotic Syndrome, or Kidney Failure

The investigators are trying to learn more about the cause of kidney diseases such as Focal Segmental Glomerulosclerosis (FSGS) and Nephrotic syndrome by studying genetics. The investigators are interested in discovering which genes play a role in causing a predisposition to FSGS/NS. The investigators also want to learn why FSGS/NS can run in families. Participation in our study involves a saliva sample and a urine sample that you can give from home. There is no cost to participate. All information is kept private and confidential. The investigators also like to include healthy volunteers (parents, spouses) if interested/available but of course this is completely optional.

VasQ External Support for Arteriovenous Fistula

This is a prospective clinical study of the VasQ external support for arteriovenous fistulas. The device is designed to improve fistula outcomes by optimizing the geometrical configuration of the fistula, influencing hemodynamics, minimizing turbulence and promote laminar flow. All patients will be implanted with the VasQ device and will be followed up for a duration of 24 months.

APOL1 Long-term Kidney Transplantation Outcomes Network (APOLLO)

The APOLLO study is being done in an attempt to improve outcomes after kidney transplantation and to improve the safety of living kidney donation based upon variation in the apolipoprotein L1 gene (APOL1). Genes control what is inherited from a family, such as eye color or blood type. Variation in APOL1 can cause kidney disease. African Americans, Afro-Caribbeans, Hispanic Blacks, and Africans are more likely to have the APOL1 gene variants that cause kidney disease. APOLLO will test DNA from kidney donors and recipients of kidney transplants for APOL1 to determine effects on kidney transplant-related outcomes.

Effects of Different Forms of a Natural Heart Hormone on Blood Pressure and Fluid Balance in Healthy Volunteers

The human heart produces hormones that help regulate blood pressure and fluid balance in the body. One of these hormones is atrial natriuretic peptide (ANP). ANP lowers blood pressure by relaxing blood vessels and increasing urinary excretion by the kidneys. Previous research has demonstrated that ANP naturally carries a small sugar molecule attached. This sugar moiety is produced endogenously and can modify the biological activity of ANP. When this sugar is present, ANP may affect blood vessels and renal function differently compared with the non-glycosylated form. The present study examines how this sugar modification alters the physiological effects of ANP. This is achieved by administering ANP, either with or without the attached sugar molecule, via intravenous infusion. The study aims to determine whether glycosylated ANP differs from the native form in its effects on blood pressure and fluid balance.

CAR-T Cell Therapy for Desensitization in Kidney Transplantation

This research study is for people who have been waiting for a kidney transplant for at least one year, and who have a cPRA of 99.5% or higher. Having a cPRA of 99.5% or higher means that your immune system would reject 99.5% of kidneys available for transplant. The study will test whether new products called Chimeric Antigen Receptor T Cells (CAR T Cells), when given with chemotherapy, is safe and will reduce cPRA. The main study will last up to 2 years: Participants will have up to 30 clinic or hospital visits over a one-year period. If a transplant takes place, there will be 9 more visits after transplant. Long term follow up is required by the Food and Drug Administration (FDA) for 15 years after receiving CAR T cell. The primary objective is to evaluate the safety and feasibility of administering CART BCMA + huCART-19 following lymphodepletion, including determination of optimal tolerated regimen (OTR) and/or recommended phase 2 regimen, according to the incidence of dose limiting toxicity (DLT) in highly sensitized patients awaiting kidney transplant.

The RENAL LIFECYCLE Trial: A RCT to Assess the Effect of Dapagliflozin on Renal and Cardiovascular Outcomes in Patients With Severe CKD

Rationale: Sodium glucose co transporter 2 (SGLT2) inhibitors are a relatively new class of agents, originally developed as oral antihyperglycemic drugs. SGLT2 inhibitors are clinically available since 2012 for the treatment of patients with diabetes mellitus type 2. Later, SGLT2 inhibitors appeared to have also specific reno- and cardioprotective effects. Remarkably, the trials that have been performed thus far excluded patients with an eGFR below 25 mL/min/1.73m2 at inclusion, prevalent dialysis patients, and kidney transplant recipients. This is unfortunate, because especially these patients are at high risk of reaching kidney failure requiring dialysis, cardiovascular complications and mortality, whereas there are only few proven effective therapies. There is emerging evidence from experimental studies and post hoc-analyses of randomized clinical trials that SGLT2 inhibitors may also be effective in preventing cardiovascular and mortality outcomes in these patients with severe CKD, including patients receiving dialysis or living with a kidney transplant. For instance, subgroup analysis of the DAPA-CKD trial comparing 624 patients with an eGFR\<30 to the remainder of the trial population with better kidney function, demonstrated that the efficacy of the SGLT2 inhibitor dapagliflozin in reducing cardiovascular, heart failure and renal outcomes persisted in the population with impaired kidney function. Furthermore, in the DAPA-CKD trial patients continued to use dapagliflozin or placebo when dialysis was initiated. In the subgroup of patients who initiated dialysis, dapagliflozin was associated with a relative risk reduction for mortality of 21%. Finally, in kidney transplant recipients, SGLT2 inhibitors have been shown to be effective in lowering HbA1c, body weight, blood pressure and stabilize kidney function, and these agents were well tolerated and safe. Taken these findings together there is a sound rationale to study the long-term reno- and cardioprotective efficacy and safety of SGLT2 inhibitors in patients with severe CKD. There are two cardiac sub-studies: the cardiac magnetic resonance imaging (MRI) sub-study and the echocardiography sub-study. The echocardiography sub-study is referred to as the "SGLT-2-inhibitors to Target Heart Failure in Peritoneal Dialysis" (STOP-HF-in-PD) study.

INCremental Dialysis to Improve Health Outcomes in People Starting Haemodialysis (INCH-HD)

The INCH-HD trial will test if incremental HD preserves the quality of life of patients and families and is a safe, practical, cost effective treatment option.

Kidney Transplant Improvement Through New Exercise Training to Increase Capacity

The goal of this clinical trial is to learn if a home-based exercise program can be safely and feasibly used to improve physical activity and physical function in adults waiting for a kidney transplant. The study will also learn how acceptable and useful this program is for participants. The main questions it aims to answer are: * Can a remote exercise program be delivered successfully to people on the kidney transplant waiting list? * Do participants follow the exercise program and wear a physical activity tracker as asked? * Is the program safe and well tolerated? Researchers will compare two groups to see if the exercise program leads to higher physical activity and better physical function: * Usual pre-transplant care with a physical activity tracker * Usual pre-transplant care plus an online exercise program Participants will: * Wear a wrist activity tracker to measure daily physical activity * Complete a one-week baseline period before being assigned to a study group * Be randomly assigned (like flipping a coin) to one of two groups * If assigned to the exercise group, take part in online exercise classes at home for 12 weeks with reminders and feedback, and then another 12 weeks without reminders and feedback * Answer questionnaires about their health, activity, and experience in the study This study may help researchers learn how to better support people waiting for kidney transplant through safe, home-based exercise programs.

Effect of Intradialytic Exercise on Left Ventricular Diastolic Function in Hemodialysis Patients

Introduction: Cardiovascular disease is the leading cause of morbidity and mortality in patients undergoing hemodialysis, largely due to structural cardiac changes associated with left ventricular diastolic dysfunction. In addition, this population has a high prevalence of sedentary behavior, which has been associated with increased mortality. Recent studies in patients with chronic kidney disease have shown that structured exercise interventions improve several parameters related to cardiovascular health. Objectives: To evaluate the effect of implementing systematic intradialytic exercise on left ventricular diastolic function. Materials and Methods: This will be a quasi-experimental before-and-after study conducted in two phases. During the first phase (control), prevalent hemodialysis patients will receive standard treatment for 16 weeks. Transthoracic echocardiography will be performed at baseline and repeated at the end of this phase to assess left ventricular diastolic function parameters. During the second phase (intradialytic exercise), participants will undergo a 16-week supervised and prescribed intradialytic aerobic exercise program consisting of intradialytic cycling. Exercise intensity will be individualized according to cardiopulmonary exercise testing (CPET), which will be performed at the beginning and end of this phase. A final echocardiogram will be obtained at the end of the intervention phase. In addition, a 6-minute walk test and a validated physical activity questionnaire will be administered monthly throughout both phases of the study.

Erector Spinae Plane Block vs Quadratus Lumborum Block for Laparoscopic Nephrectomy

Ultrasound (US) guided Quadratus Lumborum Block (QLB) is performed at the level of the 12th rib, in the parasagittal oblique plane, at the L1-L2 level. As there are modifications of the block generally local anesthetic is given between quadratus lumborum (QL) and psoas major (PM) muscles (Anterior QLB). The QLB provides a sensory block between T7 - L1. Therefore, QLBs are used to provide postoperative analgesia for abdominal, obstetric, gynecologic, and urologic surgeries. US-guided erector spinae plane block (ESPB) is performed at the level of the T11 transverse process. After visualization of the erector spinae (ES) muscle and the transverse process, local anesthetic is injected under the ES muscle. ESPB provides a sensory block of the anterior, posterior, and lateral thoracic and abdominal walls accordingly it's used for postoperative analgesia after thoracal wall repairs, thoracotomies, percutaneous nephrolithotomies, nephrectomies, and ventral hernia repairs. This study aims to compare the effectiveness of US-guided ESPB and QLB on postoperative pain control after laparoscopic nephrectomy.

A High Protein Egg White Pudding for People With Kidney Failure (HiPE KF)

The goal of this clinical trial is to compare protein supplements in patients with kidney failure on dialysis. The main questions it aims to answer are: * To determine whether the supplementation of egg white protein pudding in a population of individuals with kidney failure on dialysis is feasible. * To determine whether egg white protein pudding supplementation improves serum albumin similar to other standard nutritional supplements. * To determine the effects of the egg white protein pudding on frailty measures, dietary intakes and analytes in the blood. Participants will receive either the egg white pudding (experimental) or control (Ensure plus) at the end of their dialysis treatments 3-days per week for 12 weeks.

Shingrix in Renal Transplant Recipients

The goal of this clinical trial is to learn how well the shingles vaccine (Shingrix) works and how safe it is in adults with kidney failure who are waiting for a kidney transplant, including those who later receive a transplant. The study also aims to find out whether giving an extra (third) dose of the vaccine after transplant improves protection. The main questions it aims to answer are: How strong is the body's immune response to the vaccine at different time points (about 1 month, 2 years, and 3 years after vaccination) in people waiting for a kidney transplant? Does a third dose of the vaccine after transplant improve the immune response compared to not receiving a third dose? How long does protection from the vaccine last before and after transplant? How safe is the vaccine in this group, including whether it affects transplant-related immune markers? Researchers will compare people who receive a third dose of the vaccine after transplant to those who do not receive a third dose, as well as to results from similar groups studied in the past, to see if the extra dose improves immune protection. Participants will: Be screened to see if they can take part in the study Attend about 3 to 6 study visits over approximately 30 to 37 months Receive two doses of the shingles vaccine if they have not already been vaccinated, or complete study assessments if they were vaccinated before joining If they receive a kidney transplant during the study, be randomly assigned (by chance) to receive either a third dose of the vaccine or no additional dose Complete questionnaires, have physical exams if needed, and provide blood (and urine, if applicable) samples at study visits Take part in follow-up visits to check immune response and safety, with the option to allow samples to be stored for future research Shingrix is approved for adults aged 50 and older and for younger adults with weakened immune systems. However, giving a third dose after a kidney transplant is not standard practice and is being studied in this trial.