CLINICAL IMMUNOSUPPRESSION - KIDNEY LATE

W.J. Burlingham¹, E. Jankowska-gan¹, L. Haynes¹, M. Armbrust¹, A. Djamali², J. Pirsch³, R.M. Hofmann⁴, H. Sollinger^1
1Surgery, University of Wisconsin, Madison/WI/UNITED STATES OF AMERICA, ²Medicine And Surgery, University of Wisconsin, Madison/WI/UNITED STATES OF AMERICA, ³Medicine And Surgery, University of Wisconsin, Madison/UNITED STATES OF AMERICA, ⁴Medicine, University of Wisconsin School of Medicine and Public Health, Madison/WI/UNITED STATES OF AMERICA

Body: Introduction Immunosuppressive drug minimization trials in transplant recipients have often failed due to increased incidence of acute and chronic rejection. However, if one could predict in advance which patient-donor combinations are most likely to develop stable tolerance, the management of these patients could be geared toward drug minimization for improved renal function without substantial risk of rejection during withdrawal trials. Because of our recent finding of pre-transplant regulation between donors and recipients of HLA-identical sibling kidney transplants, and their lack of risk of problems from anti-HLA antibodies, this population was selected for a trial of mycophenolate monotherapy. Methods Patients with an HLA-identical kidney transplant for greater than one year who were currently on dual immunosuppression with mycophenolate and a calcineurin inhibitor were eligible for the trial. After enrollment, patients were randomized to a control group for monitoring donor-specific regulation using the trans-vivo DTH assay, but no change was made in medications. Alternatively, in the withdrawal arm, calcineurin inhibitor was tapered over a period of 6 months, leaving the patient on monotherapy with mycophenolate (Myfortic or Cellcept) only. Results Thirteen patients have been enrolled in the trial since 2006 out of a total projected enrollment of 30. One patient withdrew after randomization to the control arm. All 13 patients have well-functioning transplants with 1 to 4 years follow up. Serum creatinine levels have remained at pre-enrollment levels in all control patients maintained on dual immunotherapy. In the CNI withdrawal group (n=8), 3 patients have had an improvement in creatinine level over the first 12 months of the study (from 1.5 to 1.3, 1.8 to 1.3, and 1.5 to 1.1). No adverse side effects of MMF monotherapy have been noted. Conclusion While these results are still preliminary, so far they have been very encouraging. While other centers have attempted low-dose steroid monotherapy in HLA-identical sibling transplants, to our knowledge this is the first controlled clinical trial of mycophenolate as a sole immunosuppressive agent in a population of HLA-identical kidney transplant recipients. Further follow-up is needed to ensure that long-term outcomes remain in the excellent range without the use of calcineurin inhibitors or steroids.

Disclosure: All authors have declared no conflicts of interest.