CONVERSION FROM AZATHIOPRINE TO MYCOPHENOLATE MOFETIL IN PEDIATRIC RENAL TRANSPLANT RECIPIENTS
Marina Charbit, G. Guest, MF Gagnadoux, Patrick Niaudet, M. Broyer
Abstract
Marina Charbit, G. Guest, MF Gagnadoux, Patrick Niaudet, M. Broyer
Abstract
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.
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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.
Key concepts: Medicine, Prednisone, Azathioprine, Transplantation, Gastroenterology, Creatinine, Nephrotoxicity, Acute tubular necrosis