Concomitant Renal and Urinary Bladder Allograft Transplantation

Inclusion Criteria:

• Male or female patients between 1 yr. and 60 years of age.

• Subject is willing and able to give signed informed consent, or have a legallyauthorized representative who is willing and able to give consent. Informed assentwill be required for children 6-17 years of age as appropriate or warranted.

• Patients with CKD secondary to neurogenic bladder, lower urinary tract obstructionor other disorders of the urinary bladder.

• Medical need for a bladder transplant, as defined by the presence of exhibiting "hostile bladders" defined as end filling pressure or detrusor leak point pressure (DLPP) of or greater than 40 cm H20 or at below estimated bladder capacity for age,or detrusor overactivity with detrusor sphincter dyssynergia, or new onset of upperurinary tract changes (hydronephrosis, vesicoureteral reflux) in the last 12 months

• If a concomitant kidney transplant is being considered, additionally, estimated GFRless than or equal to 20 mL/min or dialysis. If GFR 20-25 mL/min would also qualifyif expected progression is rapid (>10 mL/min/year)

• Vetting and approval by the Mayo Clinic multidisciplinary transplant team (MDC) forrenal transplantation.

• Ability of subject and/or care provider to be successfully trained in cleanintermittent catheterization and bladder cycling. Or current use of CIC.

• Utilization of maximally-tolerated dose and regimen of medical therapy (e.g.anticholinergics) or failure to tolerate/contraindications to such agents.

• Psychosocial clearance: Demonstrated commitment to psychological evaluationperioperatively, in which the psychologist must confirm that the subject has thematurity and stable psychosocial environment necessary for this research study.

• Agree to avoid pregnancy for 1 year after surgery through abstinence or approvedcontraception as noted in Appendix A (female subjects only)

• If patient has a history of malignancy (with the exception of localized non-melanomaskin cancer) the patient must be at least 5 years from termination of treatmentwithout evidence of recurrent disease.

Exclusion Criteria:

• They are pregnant or breastfeeding, or planning a pregnancy during the course of thestudy, or who are of child bearing potential and not willing to continue using aneffective method of birth control (i.e. with a low failure rate of less than 1percent per year including injectables, combined oral contraceptives, someintrauterine devices, sexual abstinence, or a vasectomized partner), or

• Any contraindication to general anesthesia or evaluation reveals that the subjectcannot safely undergo general anesthesia and post-operative recovery due to severecardiovascular, pulmonary, neurological, metabolic, or rheumatologic disease (requires special consultation)

• Any contraindication or known anaphylactic or severe systemic reaction to eitherhuman blood products or materials of bovine origin

• Subjects with a current positive (>=5 mm induration for high-risk subjects;otherwise >=10 mm of induration) purified protein derivative (PPD) test are excludedunless they have completed a full course of treatment for latent TB and have anegative chest x-ray film at enrollment.

• Known history of hypersensitivity to aminoglycosides or fluoroquinolones

• Use of any investigational product within 3 months

• Prior participation in the study

• Currently smoking

• Current incarceration for any reason

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

• Any circumstance in which the investigator deems participation in the study is notin the subject's best interest

• Subjects with an ALT or AST value >3 times the upper limit of normal

• Subjects with acute or chronic abdominal skin infections and/or acute or chronicabdominal inflammatory conditions such as inflammatory bowel disease

• Subjects with uncontrolled diabetes defined as HgA1c>10, unstable cardiac and/orpulmonary disorders, or bleeding disorders

• Active malignant neoplasm (with the exception of localized non-melanoma skin cancer)that is untreated, unresponsive to available treatment, or too recently treated todetermine relapse risk.

• Surgical procedure for transplantation cannot be successfully performed foranatomical reasons

• Life expectancy with successful transplantation is estimated to be <5 years for anyreason.

• There is any other disease, physical examination finding, or clinical laboratoryresult that provides a reasonable suspicion of a disease or condition thatcontraindicates the procedure or the interpretation of results or render the subjectat high risk for treatment complications, or

• Serious or uncontrolled psychiatric illness or disorder that could compromise theirunderstanding of, or compliance with, follow-up visits/care after transplant, or

• Taking medications on specified hourly intervals that may be affected by changes torenal clearance, or

• Hypertension stage II > 99th percentile, unless they had a complete workup toexclude secondary etiologies other than being overweight, or

• Presence of severe coagulopathy, (hyper or hypo)

• Patient is not up to date on current CDC recommended vaccines