Analysis of a single-center experience with mycophenolate mofetil based immunosuppression in renal transplantation

Purpose. Acute rejection continues to be a major clinical issue in renal tr ansplantation. Three large multicenter trials have demonstrated a 50% decli ne in biopsy-proven rejection when mycophenolate mofetil (MMF) was given to renal transplant recipients with corticosteroids and cyclosporine. The pur pose of this study was to compare the 6-month outcome of renal transplant r ecipients using MMF and non-MMF based immunosuppression protocols over a 4- year period at a single center. Methods. This retrospective study analyzed three patient groups defined by their immunosuppression protocol. The first group included patients who rec eived a quadruple immunosuppression regimen of antilymphocyte induction (AT G), cyclosporine (CYA), azathioprine (AZA), and corticosteroids (CCS), and were transplanted between October 1993 and May 1995 (AZA group). The second group included patients who received a triple immunosuppression regimen of CYA, MMF, and CCS, and were transplanted between June 1995 and May 1996 (M MF group). The third group included patients who were transplanted between January 1997 and December 1997, and received an immunosuppression regimen o f CYA and MMF with a reduced CCS dosing schema (reduced steroid group (RST) ). Data were collected from a retrospective review of inpatient and outpati ent clinical records. Results. A total of 325 patients were included in the study (106 AZA, 106 M MF, 113 RST). The demographic characteristics of the three groups were simi lar; however, the mean donor age for the AZA group was 40 +/- 15.1 years ve rsus 33 +/- 14.1 years and 34 +/- 13.1 years for the MMF and RST groups, re spectively (p < 0.043). The incidence of acute, biopsy-proven rejection at 6 months was significantly less in the MMF group when compared with the AZA group [16 (15.1%) versus 35 (33%) patients, p = 0.002]. However, the incid ence of acute, biopsy-proven rejection in the RST group (35 patients, 31%) was similar to that of the AZA. group. Kaplan-Meier estimates for the cumul ative incidence of acute rejection demonstrated a significant difference be tween the MMF group and the other two groups (p = 0.0059). The AZA group ha d more severe rejection as demonstrated by the more frequent use of antilym phocyte therapy for rejection treatment (68.4% episodes) compared with the MMF (38.9%) and RST (47.6%) groups. After 6 months of follow-up, 11 patient s had lost their grafts (8, AZA; 1, MMF; 2, RST). One patient died in each of the AZA and RST groups due to hemorrhage and a pulmonary embolus, respec tively. Four AZA patients were diagnosed with a malignancy (three post-tran splant lymphoproliferative disorder, one squamous skin cell carcinoma) comp ared with 2 MMF patients (prostate cancer, basal skin cell carcinoma) and n o RST patients. Herpes tester was the only infection that occurred more fre quently in the MMF group (p = 0.03). No other differences in infection rate s were noted among the three groups. The initial length of hospital stay de clined significantly over the 4-year study period [11 +/- 4.3 d (AZA), 7.0 +/- 4.0 d (MMF), 6.2 +/- 3.3 d (RST), p < 0.001]. Total number of hospital days for the first 6 months also followed a similar declining pattern. Desp ite using intravenous cyclosporine immediately post-transplant in the MMF a nd RST groups, the incidence of delayed graft function was similar among th e three groups. Average serum creatinine at 1 month was significantly lower in the MMF group (p = 0.008), but no difference was noted at 3 and 6 month s when compared with the AZA and RST groups. Conclusion. This retrospective analysis indicates that MMF is an effective immunosuppressant. Decreased length of stay and less steroid resistant reje ctions with MMF is favorable for decreased hospital costs. However, the reb ound in rejection rate with the RST group suggests that further study is ne eded to define the optimal use of this agent in combination with others to maximize effectiveness and minimize negative side effects.