CONVERSION FROM AZATHIOPRINE TO MYCOPHENOLATE MOFETIL IN PEDIATRIC RENAL TRANSPLANT RECIPIENTS:

710 Thirty-six renal transplant recipients, 22 boys and 14 girls, (grafted from 1980 to 1998) were converted from azathioprine (AZA) to Mycophenolate Mofetil (MMF). There were 7 living-related donor grafts and 1 combined kidney-liver transplantation. Mean age at transplantation was 8,8 years (range=1-18.5 yrs). Immunosuppressive tratment was AZA and prednisone (n=4); AZA, prednisone, cyclosporine (n=28); AZA, prednisone, FK506 (n=6). Initial doses of MMF were 600 mg/m2 b.i.d or 300 mg/m2 b.i.d for patients (pts) on FK506. Mean follow-up was 12.6 months (range=1-30). The pts were retrospectively divided into 3 groups according to the time of conversion to MMF related to the age of transplantation. Group 1 (n=8): Conversion to MMF was made during the first year post transplant (mean=4.1 mths). Two pts had cyclosporine nephrotoxicity, 1 had FK506 nephrotoxicity, 4 pts acute rejection (3 with FK506). All were biopsy proven. One pt had psychological intolerance to prednisone. Mean creatinine at the initiation of MMF was 128 μmol/l and decreased to 87 μmol/l after a mean follow-up of 14.3 mths. One pt had acute rejection 18 mths after MMF initiation. Group 2 (n=21): Conversion to MMF was made 1 to 10 yrs post transplant (mean=4.5 yrs). Seventeen pts had chronic transplant nephropathy (CTN) grade I to II, 2 had recurrent nephropathy, 1 had cyclosporine nephrotoxicity, and 1 had an anemia with AZA. Mean creatinine at initiation of MMF was 137 μmol/l. Six pts had a 10% to 25% decrease in creatinine level (follow-up 2.5 to 14 mths), creatinine level was unchanged in 12 pts, and 2 pts resumed dialysis. Anemia was corrected after MMF conversion. Group 3 (n=7): Conversion to MMF was made ≥10 years post transplant (mean=12.6 yrs). All pts had severe CTN. Mean creatinine at initiation of MMF was 255 μmol/l. One pt had a decrease in creatinine level (190 to 160 μmol/l), in 4 pts creatinine level remained unchanged, renal function deteriorated in 1, and 1 resumed dialysis due to non compliance. Of the 36 pts, 21 had 1 or more adverse events: diarrhea (16), nausea and vomiting (4), anemia (6), herpes zoster (2), pneumonia (1), urinary tract infection (1), HBV replication with cytolysis (1). These events led to discontinuation of MMF in 4 pts, interruption in 2, and dose reduction in 17. We conclude that conversion from AZA to MMF in pts with cyclosporine nephrotoxicity, acute rejection, or CTN grade I or II, results in stabilization or improvement in renal function in short term follow-up. However, conversion in pts with severe CTN offers no benefit. High incidence of MMF-related gastrointestinal adverse events necessitates reduced dosages in 50% of pts.