Concomitant Renal and Urinary Bladder Allograft Transplantation
Abstract
The urinary bladder is designed to store urine under low pressures and to expel urine during voiding. There are many clinical conditions where the urinary bladder either does not function as it should, is absent, or has been surgically removed. Dysfunctional bladders can happen in patients with spinal cord injuries, spina bifida, diabetes, interstitial cystitis, stroke, brain tumors, mithochondrial diseases, rheumatoid arthritis, radiation injury, treatment for cancer, and hundreds of other diagnoses. Patients may be born without bladders or with nonfunctioning bladders and patients may have their bladders removed surgically because that bladder does not function, because of bladder or prostate cancers, or because of traumatic injury (such as may be suffered during active military service). In some of the above patients, the absence of a urinary bladder or of an adequately functioning urinary bladder could lead to secondary kidney injury either from increased pressures, backflow of urine, or recurrent urinary tract infections. Furthermore, in some diagnoses, such as rheumatoid arthritis and diabetes, there could be injury to both the kidneys and the bladder at the same time. If this kidney injury progresses, patients can go into kidney failure and would require a kidney transplant. If the urinary bladder is not repaired or reconstructed either before or at the time of kidney transplant, the kidney transplant can be damaged and lost. Presently the only tissue that surgeons have available to either create or reconstruct urinary bladders are segments of intestine from the patient. Intestinal segments are physiologically absorptive tissues and placing them in contact with urine has significant short- and long-term problems. Specifically, patients with intestine in the urinary tract can have repeat urinary infections, urinary stones, long-term nutritional deficiencies (vitamin B12), severe electrolyte problems, worsening of kidney injury, and aggressive types of cancer. Previous attempts over the last 20 plus years at generating bladder tissue substitutes through bioengineering have failed and have had catastrophic consequences and complications. Therefore, there is a significant need for better options for these patients. We propose a completely novel and innovative surgical technique for urinary bladder replacement, which could positively impact thousands of pediatric and adult patients requiring bladder substitution or reconstruction. What is different about our study is that we propose to use a transplanted urinary bladder with its own blood supply and this has never been done in a human trial. Our objective in this Phase 1 clinical study is to establish the feasibility and safety of a kidney and urinary bladder transplant in patients requiring both a renal transplant and bladder reconstruction (or neo-construction). In Specific Aim 1, we will determine if a concomitant renal and vascularized urinary bladder allograft is well-tolerated in patients in the acute setting. In Specific Aim 2, we aim to determine rejection rates in vascularized urinary bladder and whether it will impact rejection rate for the concomitant renal transplant. In Specific Aim 3, we will study the function of vascularized bladder allotransplants in patients and complications in comparison to current existing methods of treating such bladder dysfunction. We hypothesize that a concomitant renal and vascularized urinary bladder allograft transplant will be a safe, well-tolerated, and effective intervention in patients facing genitourinary dysfunction due to congenital or acquired anomalies. This project addresses the following topic areas: Diabetes, interstitial cystitis, mitochondrial diseases, tissue regeneration, polycystic kidney disease, and nutritional optimization. It could have significant improvement both to the quality of life and long-term risks to patients needing bladder reconstruction and kidney transplant as intestin
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Mar 10, 2021
- Source ID
- W81XWH2010662
Entities
People
- Patricio Gargollo
Organizations
- Mayo Clinic
- United States Army