Experience of FK506 immune suppression in pediatric heart transplantation: a study of long-term adverse effects.

BACKGROUND

Immunosuppression with FK506 for pediatric heart transplantation has been used in this institution since 1989. This study reports the unique toxicity of this macrolide agent in these heart transplant recipients.

METHODS

Between October 1989 and August 1994, 49 patients were managed with FK506, which was the initial primary agent in 38 patients. The remaining 11 were switched from cyclosporine A because of persistent rejection or side effects from the cyclosporine A or prednisone. Data were obtained retrospectively from medical records.

RESULTS

Mean duration of follow-up was 29 months (median 37 months, range 3 to 96 months). Twenty-nine patients (59%) were receiving FK506 alone; 20 patients (41%) were receiving additional treatment with azathioprine, prednisone, or methotrexate. There were seven deaths. Twenty patients (41%) had elevated creatinine levels between 1 to 2 mg/dl. Five patients (11%) had levels greater than 2 mg/dl. Two patients with preexisting renal dysfunction while receiving cyclosporine A had chronic renal failure 32 and 36 months after switching to FK506 and required kidney transplantation. Hyperkalemia was a persistent finding in 26 patients. Of eight patients with hypertension, four had preexisting disease while receiving cyclosporine A; two had impaired renal function, and two were receiving prednisone. Severe anemia developed in eight patients (16%), two of whom had parvovirus. Moderate anemia developed in 21 patients (43%). Eosinophilia occurred in 19 patients; 11 of 19 patients (58%) had allergic symptoms. There was one case of diabetes mellitus. There were 12 significant infections with four infection-related deaths. Lymphoproliferative disease was noted in three patients, two of whom survived. Gastrointestinal symptoms, including chronic diarrhea, recurrent abdominal pain, and reflux esophagitis were present in 10 patients.

CONCLUSIONS

In our experience, anemia, renal toxicity, hyperkalemia, chronic diarrhea, and allergies were the most common adverse effects of FK506. Unlike cyclosporine A, hypertension, gingival hyperplasia, coarsening of facial features, and hirsutism were not seen.