The purpose of this study is to establish if concomitant renal and vascularized urinary bladder allograft transplantation is feasible.
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 legally authorized representative who is willing and able to give consent. Informed assent will be required for children 6-17 years of age as appropriate or warranted.
Patients with CKD secondary to neurogenic bladder, lower urinary tract obstruction or 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 upper urinary tract changes (hydronephrosis, vesicoureteral reflux) in the last 12 months
They are pregnant or breastfeeding, or planning a pregnancy during the course of the study, or who are of child bearing potential and not willing to continue using an effective method of birth control (i.e. with a low failure rate of less than 1 percent per year including injectables, combined oral contraceptives, some intrauterine devices, sexual abstinence, or a vasectomized partner), or
Any contraindication to general anesthesia or evaluation reveals that the subject cannot safely undergo general anesthesia and post-operative recovery due to severe cardiovascular, pulmonary, neurological, metabolic, or rheumatologic disease (requires special consultation)
Any contraindication or known anaphylactic or severe systemic reaction to either human 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 excluded unless they have completed a full course of treatment for latent TB and have a negative chest x-ray film at enrollment.
Single group
Concomitant Renal and Urinary Bladder Allograft Transplantation
Procedure/SurgeryThis is a single-center, prospective, single-group unblinded phase I study that will enroll subjects with chronic kidney disease secondary to bladder dysfunction or bladder absence that is refractory to medical treatment and requires surgical intervention to prevent long-term sequelae. 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 contruction.
Establish if concomitant renal and vascularized urinary bladder allograft transplantation is feasible.
The primary endpoint will be bladder compliance and/or the end fill pressure at bladder capacity as assessed by standardized urodynamic measures at 12 months and yearly until year 4 Urodynamic measures assessed multiple times in each subject over the follow up period will be modeled with linear mixed effects models. A discrete time relationship will estimate the mean bladder compliance or end fill pressure at 12 months and yearly until year 4. Models will adjust for baseline value, and random intercepts and slopes will be considered using model fit criteria. From this linear mixed effects model, we estimate the expected change from baseline to 12 months (and yearly until year 4), adjusting for baseline value. Results will be reported as estimated 12 month mean with confidence interval.
Study the long term function of vascularized bladder allotransplantation in patients receiving a concomitant renal and bladder graft
End-filling pressure at age-related nomogram derived bladder capacity at baseline, 6 months, 12 months, and 24 months. a. Ratio of measured bladder volume to age-related nomogram derived bladder capacity at baseline, 2,4, 6, 9, 12, and 48 months Filling pressure at 25, 33, 50, 66, and 75 percent of the age-related nomogram-derived bladder capacities Neurogenic detrusor overactivity Frequency of incontinence episodes . 3. Individual subject data including resolution of vesicoureteral reflux, hydronephrosis or recovery of renal function . 4\. Evaluating the effect of improved genitourinary function on overall health and mental health using QoL questionaires 5. Rejection and other histological changes will be monitored with protocol biopsies at month 2, 4, 12, 24, 48 and annually until year 4. For cause biopsies for clinical changes such as decreased compliance or hematuria will also be performed.
Incidence of all serious adverse events including unanticipated adverse events
All adverse events will be captured and graded for severity using Common Terminology Criteria for Adverse Events (CTCAE) scale.
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