2010 - TTS International Congress


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Use of mTOR inhibitors and MPA I

113.9 - Immunosuppressive regimen for first kidney or kidney/pancreas transplant significantly impacts sensitization at the time of second transplantation.

Presenter: Kyle, Dawson, Houston, United States
Authors: Dawson K., Patel S., Knight R., Gaber A.

IMMUNOSUPPRESSIVE REGIMEN FOR FIRST KIDNEY OR KIDNEY/PANCREAS TRANSPLANT SIGNIFICANTLY IMPACTS SENSITIZATION AT THE TIME OF SECOND TRANSPLANTATION.

USE OF MTOR INHIBITORS AND MPA I

K.L. Dawson1, S.J. Patel2, R.J. Knight3, A.O. Gaber3
1Department Of Pharmacy, The Methodist Hospital, Houston/UNITED STATES OF AMERICA, 2Department Of Pharmacy, The Methodist Hospital, Houston/TX/UNITED STATES OF AMERICA, 3Department Of Surgery, The Methodist Hospital, Houston/TX/UNITED STATES OF AMERICA

Body: Introduction: A leading indication for kidney transplantation is failure of a previous renal allograft. Increased sensitization, measured by Panel Reactive Antibodies (PRA), results in prolonged waiting times for transplantation and makes it difficult, or in some cases, virtually impossible to place an organ without a positive crossmatch. This study aims to identify factors at the time of first transplant leading to increased sensitization in patients undergoing retransplantation. Methods: A review of UNOS kidney/pancreas transplant dataset #072309-2 (created 5/26/09) was performed. Retransplanted patients were identified and linked with the primary transplant event. Discharge immunosuppressive regimens from the first transplant event were also linked according to transplant ID. All retransplanted patients with a primary transplant date of 1999 or later, receiving either Thymoglobulin®, daclizumab or basiliximab (IL2-RA), or no induction at first transplant, and with a peak PRA at the time of first transplant of <20% were included. Subjects with missing or discrepant age, gender, transplant date, PRA values, or immunosuppression information were excluded. The final dataset was analyzed to identify factors that significantly impacted change in PRA (delta PRA) from the time of first to second transplant. Peak PRA values at the time of each transplant were used. Independent variables significantly associated with a delta PRA of 20% or lower were identified using logistic regression. Results: The final patient population (n=4218) had a mean (SD) age of 39±14 years at first transplant, and was 61% male, 73% Caucasian and 16% African American (AA). Initial transplant type was kidney (88.9%), simultaneous kidney-pancreas (8.7%), and pancreas alone (1.3%). Mean time between transplants was 3.2±2.5 years. Mean PRA at the time of first transplant was 1.9±3.6% and the mean delta PRA was 26±37% from first to second transplant. Induction immunosuppression for the primary transplant event was no induction (43%), Thymoglobulin® (24%), and IL2-RA (33%). Discharge maintenance immunosuppressive therapy consisted of cyclosporine (30%) or tacrolimus (57%) combined with mycophenolate mofetil/sodium (MMF) (73%), rapamycin (13%), or azathioprine (3%) and steroids (80%). On univariate analysis, variables at the time of first transplant found to be significantly associated with a lesser delta PRA were Thymoglobulin® induction (23.9% vs. 26.9%, p=.004), tacrolimus maintenance (22.6% vs. 30.4%, p<.0001) and MMF maintenance (25.1 vs. 28.3, p=0.01). Variables significantly associated with a greater delta PRA were IL2-RA induction (28.0% vs. 25.0%, p=0.02), cyclosporine maintenance (30.5% vs. 24.0%, p<0.001), and AA ethnicity (39.3% vs. 23.4%, p<0.001). Non-significant variables were age, gender, PRA at first transplant, rapamycin maintenance and steroid maintenance. Factors favoring a delta PRA < 20% in the multivariate analysis included Thymoglobulin® vs. IL2-RA induction (OR 0.766, p=0.007), tacrolimus vs. cyclosporine maintenance (OR 0.588, p<0.0001), and non-AA vs. AA ethnicity (OR 0.479, p<0.0001). Conclusion: Thymoglobulin® induction and tacrolimus maintenance therapy for primary kidney or pancreas transplant results in significantly reduced sensitization at the time of retransplantation, while AA race is associated with a greater change in PRA. This data suggests a possible long-term benefit to using Thymoglobulin® induction and tacrolimus maintenance therapy in primary renal or pancreas transplants with a low PRA.

Disclosure: All authors have declared no conflicts of interest.


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