ABSTRACT
BACKGROUND: Despite evidence of favorable long-term effects of mycophenolate mofetil (MMF) in renal transplantation, its introduction at different times posttransplant has not been studied in large cohorts. METHODS: Single-organ renal allograft recipients (n=2217) who had MMF introduced 6 months to more than 20 years posttransplantation for various reasons were included in TranCept Switch, a multicenter, noninterventional, observational 4-year study. Changes in renal function before and after the introduction of MMF were analyzed. RESULTS: MMF was introduced because of renal function decline in 43% of patients and poor tolerability with previous treatment in 23% of patients. The change in slope of the calculated glomerular filtration rate (modification of diet in renal diseases formula) regression line before and after MMF initiation was +2.01 mL/min per year (P<0.001) on average. The greatest benefit was noted in patients who received MMF because of renal function decline and in whom calcineurin inhibitor treatment was subsequently reduced or withdrawn (+3.09 mL/min per year). Time from transplantation to MMF introduction influenced the glomerular filtration rate at MMF initiation (slow progressive deterioration) but not the direction of the slope change, which was positive even for late introduction. CONCLUSION: MMF introduction may be associated with improvement or stabilization of renal function even several years after transplantation.
Subject(s)
Immunosuppressive Agents/administration & dosage , Kidney Transplantation/methods , Mycophenolic Acid/analogs & derivatives , Adult , Cohort Studies , Drug Administration Schedule , Female , Glomerular Filtration Rate/drug effects , Graft Rejection/etiology , Graft Survival/drug effects , Humans , Kaplan-Meier Estimate , Kidney Transplantation/adverse effects , Kidney Transplantation/physiology , Male , Middle Aged , Mycophenolic Acid/administration & dosage , Proportional Hazards Models , Prospective Studies , Time Factors , Young AdultABSTRACT
Maintenance immunosuppression with cyclosporine (CsA) is associated with nephrotoxicity, hyperlipidemia, and hypertension. This long-term study (core study + 4 yr of follow-up) investigated the long-term efficacy and safety of CsA withdrawal from a mycophenolate mofetil (MMF)-based regimen. Seventy-seven patients were maintained on CsA, MMF, and steroids (CsA-MMF group), and 74 were given a CsA-free regimen of MMF and steroids (MMF group). Serum creatinine and creatinine clearance were measured at 6-month intervals. Patient and graft survival, acute rejection episodes, malignancies, BP, and lipid profile were also recorded. At 5 yr, patient and graft survival was 93 and 88%, respectively, for the MMF group and 95 and 92%, respectively, for the CsA-MMF group. During follow-up, seven MMF patients experienced acute rejection episodes compared with one CsA-MMF patient (P = 0.0283). Nine grafts were lost to chronic rejection in the MMF group versus three in the CsA-MMF group. No demographic or immunologic characteristics were associated with acute or chronic rejection in the MMF group, but the doses of both MMF and steroids decreased significantly between 1 and 5 yr. The MMF group showed a trend toward improved creatinine clearance (67.4 versus 61.7 ml/min; P = 0.0500). Withdrawal of CsA from an MMF-containing immunosuppressive regimen resulted in an increased risk for acute rejection episodes and graft loss as a result of rejection throughout the 5-yr study period. The creatinine clearance-confirmed improvement in renal function observed at year 1 was maintained at 5 yr BP and cholesterol levels were well controlled in both groups.
