CLINICAL IMMUNOSUPPRESSION - KIDNEY LATE

H. Kishikawa, T. Souda, S. Yonemoto, K. Yamanaka, A. Okuno, T. Hirai, N. Fujii, K. Nishimura, Y. Ichikawa
Department Of Renal Transplantation Center, hyogo pref. nishinomiya hospital, nishinomiya, hyogo/JAPAN

Body: INTRODUCTION: Corticosteroids are considered to be essential for treatment of renal transplant recipients in the initial period after transplantation. However, since steroid treatment is known to be associated with a number of harmful side effects, such as diabetes, hypertension, hyperlipidemia, and osteoporosis, steroid withdrawal has been attempted in many centers. However, steroid withdrawal regimens are reported to be associated with increased risks of acute and chronic allograft rejection. To reduce the likelihood of acute rejection, a major problem in kidney transplantation, we investigated the efficacy and safety of immunosuppressive regimens that included tacrolimus (Tac) or cyclosporine (CsA), with basiliximab, mycophenolate mofetil (MMF) or mizoribine (MZR), and low-dose steroid administration (prednisone at 2.5 mg/day). METHODS: Between August 2005 and December 2009, 76 patients with end-stage renal disease received kidney transplants at the Hyogo Prefectural Nishinomiya Hospital, of whom 68 agreed to participate in this study with written consent. In all patients, basiliximab was administered as induction therapy as well as a calcineurin inhibitor (Tac or CsA), MMF or MZR, and steroid administration was conducted as maintenance therapy. Corticosteroid therapy consisted of perioperative intravenous methylprednisolone (250 mg intraoperatively, 50 mg on days 1-5), followed by oral doses of prednisone gradually tapered to less than 2.5 mg/day within 2 months. Patients with stable graft function (serum creatinine level <2.0 mg/dl) without proteinuria were eligible to participate in this study. In seventeen patients with impaired graft function or proteinuria, prednisone was not tapered to 2.5 mg, but rather maintained at 5 mg/day. A total of 51 patients with stable graft function were maintained with prednisone at 2.5 mg/day, and their trough levels of Tac and CsA were 4-5 ng/ml and 100 ng/ml, respectively. We assessed graft survival, episodes of rejection, graft function, and side effects in those 51 patients. RESULTS: For the 51 subjects, the mean age at time of transplantation was 46.4 years (19-70) and mean observation period was 24.9 months (2-54). The mean maintenance dose of prednisone at 1, 2, and 3 years post-transplantation was 2.2, 2.5, and 2.4 mg/day, respectively. Patient survival after 1, 2, and 3 years was 98.0%, 95.2%, and 95.2% respectively. Two patients died of cerebral bleeding and pneumocystis pneumonia with a functioning graft. Death-censored graft survival was 100% and the mean serum creatinine level remained stable. The cumulative incidence of acute rejection post-transplantation was 11.2%, 17.0%, and 17.0% at 1, 2, and 3 years, respectively. In 3 patients, the daily dose of prednisone was increased to 5 mg after rejection episodes. Among the recipients with adverse events, 6 had CMV infections. Values for mean blood pressure, total cholesterol level, and triglyceride level remained stable, and only 3 patients had new onset diabetes after transplantation. CONCLUSIONS: Our low-dose steroid immunosuppressive regimen demonstrated favorable results, by reducing the number of acute rejection incidences without causing severe adverse events.

Disclosure: All authors have declared no conflicts of interest.