Kidney + Bladder Transplant for Organ Failure

Recruiting at 1 trial location

Overseen By Patricio Gargollo, MD

Age: < 65

Sex: Any

Trial Phase: Phase < 1

Sponsor: Mayo Clinic

Must be taking: Anticholinergics

Must not be taking: Aminoglycosides, Fluoroquinolones

Disqualifiers: Pregnancy, Uncontrolled diabetes, Smoking, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

Duration: Surgical procedure with immediate post-operative care

30 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if a combined kidney and bladder transplant can effectively treat individuals with severe kidney and bladder issues. It targets those with chronic kidney disease (CKD) caused by bladder problems, experiencing complications like frequent urinary issues and the need for bladder reconstruction. Suitable candidates are those facing bladder problems requiring medical attention and considering a kidney transplant. As an Early Phase 1 trial, this research seeks to understand how the treatment functions in people, offering participants the opportunity to be among the first to receive this innovative treatment.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications. However, if you are taking medications that are affected by changes in kidney function, this might be a concern. It's best to discuss your specific medications with the trial team.

What prior data suggests that this transplantation method is safe?

Research has shown that the safety of performing kidney and bladder transplants together in one surgery is still under exploration. As a new method, limited information exists on patient outcomes. Since this study is in an early stage, researchers are beginning to test this treatment in humans to assess its safety. Early studies primarily focus on safety and aim to identify any potential side effects.

Successful bladder transplants in other cases suggest some level of safety. However, because this combination of treatments is new, specific risks and side effects remain under investigation. Prospective participants should discuss potential risks with the study team, as they continue to gather information on the treatment's safety. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about the concomitant renal and urinary bladder allograft transplantation because it offers a new approach to managing kidney and bladder failure together. Unlike the standard practice of reconstructing the bladder with intestinal segments after a kidney transplant, this treatment uses a donor bladder. This could potentially lead to better long-term outcomes by preserving natural bladder function and reducing complications associated with using intestinal tissue. By addressing both organ failures simultaneously, this innovative method might improve the quality of life for patients with severe kidney and bladder conditions.

What evidence suggests that concomitant renal and urinary bladder allograft transplantation could be effective for organ failure?

Research has shown that the first bladder transplant yielded promising results. The kidney transplant quickly began producing a significant amount of urine, and the patient's kidney function improved immediately. This trial will evaluate the effectiveness of performing both kidney and bladder transplants together for individuals with serious kidney and bladder issues. This procedure might offer new hope for restoring normal function without using intestinal parts to rebuild the bladder. Although this method is still under study, early results are encouraging for those requiring both kidney and bladder transplants. ^{1 2 3 5 6}

Who Is on the Research Team?

Patricio C. Gargollo, M.D.

Principal Investigator

Mayo Clinic

Are You a Good Fit for This Trial?

This trial is for individuals aged 1-60 with severe kidney disease or bladder conditions needing both a kidney and bladder transplant. They must be able to perform self-catheterization, have stable mental health, and not be pregnant. Excluded are those with certain allergies, active infections, recent cancer treatments (except skin cancer), uncontrolled diabetes or hypertension, psychiatric issues affecting compliance, or any condition making surgery too risky.

Inclusion Criteria

I can sign the consent form myself, or have someone legally allowed to do it for me.

My kidney function is very low, possibly needing a transplant.

I am between 1 and 60 years old.

Exclusion Criteria

I do not have a current positive TB skin test or have completed treatment for latent TB with a negative chest x-ray.

Unwillingness, inability, or unlikely compliance of individual and/or primary caregiver with study related schedules procedures, management, or follow -up in the opinion of the PI and/or co-investigators

Current incarceration for any reason

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo concomitant renal and vascularized urinary bladder allograft transplantation

Surgical procedure with immediate post-operative care

Follow-up

Participants are monitored for bladder compliance and end fill pressure at bladder capacity, as well as other health outcomes

48 months

Multiple visits for urodynamic measures and biopsies at 2, 4, 6, 9, 12, 24, and 48 months

Long-term monitoring

Participants are monitored for long-term function of vascularized bladder allotransplantation and overall health impact

Annually until year 4

What Are the Treatments Tested in This Trial?

Interventions

• Concomitant Renal and Urinary Bladder Allograft Transplantation

Trial Overview The study tests the feasibility of performing simultaneous kidney and vascularized urinary bladder transplants in patients who need them due to severe organ dysfunction. It aims to determine if this combined procedure can be done safely and effectively.

How Is the Trial Designed?

Group I: Intervention group Experimental Treatment 1 Intervention

Patients will undergo a cadaveric donor bladder transplant in addition to or after their kidney transplant rather than using intestinal segments for bladder reconstruction or construction.

Concomitant Renal and Urinary Bladder Allograft Transplantation is already approved in United States for the following indications:

Approved in United States as Concomitant Renal and Urinary Bladder Allograft Transplantation for:

• End-stage renal disease requiring kidney transplantation and bladder reconstruction

Who Is Running the Clinical Trial?

Mayo Clinic

Lead Sponsor

Trials

3,427

Recruited

3,221,000+

Published Research Related to This Trial

In a study of 58 pediatric patients, three with severe bladder dysfunction who underwent augmentation cystoplasty prior to renal transplantation showed normal kidney function and no complications at follow-up periods of 13 to 49 months.

Augmentation cystoplasty appears to be a safe and effective treatment for these patients, with all subjects remaining continent and experiencing manageable urinary tract infections without affecting kidney graft function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Renal transplantation in children with augmentation enterocystoplasty. Aki, FT., Besbas, N., Ozcan, O., et al.[2006]

In a study of 7 patients with severe bladder dysfunction who underwent intestinal bladder augmentation before renal transplantation, the graft survival rate was 100% with good function observed over an average follow-up of 48 months.

Most patients (6 out of 7) achieved urinary continence and were able to void spontaneously, indicating that bladder augmentation can be a safe and effective procedure for those needing renal transplants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enterocystoplasty and renal transplantation. Martín, MG., Castro, SN., Castelo, LA., et al.[2019]

Renal transplantation in patients with reconstructed bladders has higher urologic complications, but overall graft and patient survival rates are similar to those with non-reconstructed bladders, based on a review of 25 articles.

It is recommended that bladder reconstruction be done prior to kidney transplantation when necessary, as this may help manage complications more effectively.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Renal transplantation in children with reconstructed bladders. Franc-Guimond, J., González, R.[2022]

In a 10-year review of 10 renal transplant recipients with augmented bladders, the procedure was found to be safe, with no patient deaths and 9 out of 10 grafts functioning well after an average follow-up of 27 months.

Despite some complications, including 10 episodes of urosepsis in four patients, only one graft was lost, indicating that renal transplantation in this patient group can be successfully managed with careful monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Renal transplantation in patients with an augmentation cystoplasty. Power, RE., O'Malley, KJ., Khan, MS., et al.[2019]

Kidney transplant recipients with prior bladder surgery face a significantly higher risk of graft failure and increased urinary complications, with a hazard ratio of 3.57 for graft survival, indicating a need for careful recipient selection.

Post-operative complications were notably higher in recipients with bladder dysfunction (35%) and those with bladder substitutes (52.3%), compared to only 12.8% in those with normal bladder function, highlighting the importance of monitoring these patients closely after transplantation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-Term Outcomes of Kidney Transplant Recipients with Bladder Dysfunction: A Single-Center Study. Srinivasan, D., Stoffel, JT., Mathur, AK., et al.[2019]

In a study of 25 patients with bladder dysfunction who underwent renal transplantation after augmentation cystoplasty, 80% of the transplanted kidneys were functioning well at an average follow-up of 53.2 months, indicating good long-term efficacy of the procedure.

The study found that augmentation cystoplasty is a safe and effective way to improve bladder function, allowing for successful renal transplantation, with a 5-year graft survival rate of 78% despite some complications like urinary infections and ureteral stenosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Augmentation cystoplasty in renal transplantation: a good and safe option--experience with 25 cases. Nahas, WC., Mazzucchi, E., Arap, MA., et al.[2019]

In a study comparing 9 kidney transplant recipients who underwent simultaneous bladder augmentation (BA-KT) with 22 who had kidney transplants only, the BA-KT group showed better early graft function, with a higher estimated glomerular filtration rate (96.5 mL/min vs. 79.4 mL/min) within the first 6 months.

However, the BA-KT group experienced significantly higher rates of urinary tract infections (100% vs. 23% in the KT only group) and complications related to posttransplant care, leading to a notable decline in graft function by the fifth year, with only 66% of grafts functioning compared to 100% in the KT only group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term Outcome of 1-step Kidney Transplantation and Bladder Augmentation Procedure in Pediatric Patients. Cleper, R., Ben Meir, D., Krause, I., et al.[2022]

Kidney transplantation in patients with a reconstructed urinary tract has a higher rate of complications, including urinary tract infections and the need for surgical interventions, but does not lead to graft loss due to surgical issues.

Despite the increased complication rate, the long-term outcomes are promising, with a 100% one-year patient and graft survival rate, and 77.8% of grafts functioning after five years, comparable to those with normal urinary bladders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term outcome of kidney transplantation in patients with a urinary conduit: a case-control study. Slagt, IK., Ijzermans, JN., Alamyar, M., et al.[2021]

In a study of 24 kidney transplant recipients with urinary tract reconstructions, graft survival was 83%, which is comparable to the 97% survival rate in matched control recipients, indicating that reconstruction does not significantly compromise kidney survival.

However, patients with urinary tract reconstructions experienced a much higher rate of urinary tract infections (91.7% vs. 45.6% in controls), which often required in-hospital treatment, highlighting the need for careful management and potential prophylactic measures in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Factors predisposing to urinary tract infections in adult kidney allograft recipients with lower urinary tract reconstruction. Pazik, J., Wazna, E., Lewandowski, Z., et al.[2022]

The study demonstrated that vascularized total bladder transplantation alongside kidney transplantation is feasible, as all grafts showed good blood supply and normal oxygen saturation during the observation period.

While one recipient experienced thrombosis leading to reduced urinary output, the other two recipients maintained normal bladder function, suggesting that with careful monitoring, this procedure could serve as a viable option for bladder augmentation or replacement.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combined kidney and vascularized total bladder transplantation: experience in an animal model. Torino, G., Capozza, N., Diomedi Camassei, F., et al.[2015]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04626167?cond=Bladder%20exstrophy&aggFilters=status:not%20rec%20ava&viewType=Table&rank=4

Concomitant Renal and Urinary Bladder Allograft ... The purpose of this study is to establish if concomitant renal and vascularized urinary bladder allograft transplantation is feasible. Detailed Description.

2. withpower.com withpower.com/trial/kidney-bladder-transplant-for-organ-failure-97449

Kidney + Bladder Transplant for Organ Failure This trial is for individuals aged 1-60 with severe kidney disease or bladder conditions needing both a kidney and bladder transplant.

3. centerwatch.com centerwatch.com/clinical-trials/listings/NCT04626167/concomitant-renal-and-urinary-bladder-allograft-transplantation

Concomitant Renal and Urinary Bladder Allograft ... The purpose of this study is to establish if concomitant renal and vascularized urinary bladder allograft transplantation is feasible.

4. clinicaltrials.gov clinicaltrials.gov/study/NCT04626167

Concomitant Renal and Urinary Bladder Allograft ... The purpose of this study is to establish if concomitant renal and vascularized urinary bladder allograft transplantation is feasible. Detailed Description.

5. renalandurologynews.com renalandurologynews.com/features/first-bladder-transplant/

First Bladder Transplant Offers New Hope for Patients ... “The kidney [transplant] immediately made a large volume of urine, and the patient's kidney function improved immediately,” Nima Nassiri, MD, a ...

6. centerwatch.com centerwatch.com/clinical-trials/listings/NCT04626167/concomitant-renal-and-urinary-bladder-allograft-transplantation?page=83&id=226&slug=kidney-disease

Concomitant Renal and Urinary Bladder Allograft ... The purpose of this study is to establish if concomitant renal and vascularized urinary bladder allograft transplantation is feasible.