CYCLOSPORINE LEVEL CHANGES IN PEDIATRIC RENAL TRANSPLANT (TX) PATIENTS DURING GROWTH HORMONE THERAPY.

Abstract

57 Pediatric renal Tx patients with persistent growth failure may be treated with Growth hormone (GH). However, GH therapy has been associated with increases in serum creatinine levels and possible rejection. Recent studies in humans have revealed an increase in cytochrome P450 activity (CYP3A4 hepatic enzyme) with GH treatment. However, there have been no studies to examine the effect of GH treatment on Cyclosporine (CSA) metabolism. Therefore, 15 patients (12 boys and 3 girls) with 11 cadaveric and 4 living-related well-functioning grafts (ages from 5-14 yrs), who received GH therapy at least 1 year after renal Tx, were studied retrospectively. Measurements of whole blood 12 hour trough CSA levels by the TDx monoclonal assay were examined at the time of GH therapy initiation and at 3, 6, 9, and 12 months pre and post-GH therapy. The initial average CSA dose was 6.1±3.1 mg/kg/day; the average prednisone dose was 0.12±0.04 mg/kg/day. Other immunosuppressive therapy included lmuran (Azathioprine) at 1.2±0.2 mg/kg/day or Cellcept (Mycophenolate mofetil) at 35.3±12.1 mg/kg/day. GH therapy was discontinued in one patient after 4 months of treatment because of creatinine elevation and acute rejection, confirmed by renal biopsy. In another patient, GH treatment was discontinued after 11 months for acute rejection, also confirmed by renal biopsy. Of the remaining 13 patients, 9 patients completed 12 months of GH treatment, 3 patients completed 9 months and 1 patient completed 6 months of treatment. CSA dose adjustment to maintain appropriate immunosuppression was done when indicated. A significant decrease in CSA level (p< 0.05) was noticed at 3 and 12 months post-GH treatment compared with baseline, in the absence of a significant change in the weight-adjusted CSA dose in mg/kg/day. Paired Two-tailed Student t test was used (Table).Using ANOVA (single factor), CSA levels at 3, 6, 9 and 12 months during GH therapy were significantly lower than baseline, 3, 6, 9 and 12 months prior to GH therapy (p=0.0145), at a time when no difference in CSA dose was detected. These results suggest that GH treatment decreases CSA levels. Increasing CSA dosage may be needed during GH treatment to prevent acute or subclinical rejection.