INITIAL EXPERIENCE WITH FK506 (TACROLIMUS) IN PEDIATRIC RENAL-TRANSPLANT RECIPIENTS

Purpose: The efficacy and safety of the new immunosuppressant agent, F K506 (tacrolimus), was assessed in pediatric renal transplant recipien ts over a mean 12-month follow-up period. Methods: Twenty pediatric re nal transplant recipients received oral FK506 therapy (0.3 mg/kg/d) in combination with azathioprine (1 to 2 mg/kg/d) and low-dose prednison e as primary therapy (n = 11) or were converted from cyclosporine-base d therapy (n = 9) for complications including cyclosporine toxicity in = 2), acute refractory rejection (n = 4), and chronic rejection (n = 3). Patients were then followed-up prospectively to evaluate effective ness of therapy and complications. Results: In the primary treatment g roup, 45% of patients had one or more rejection episodes. Two required OKT3 therapy (18%) for persistent rejection, with one (9%) graft loss at 3 months. All other episodes were treated effectively with FK506 d ose adjustment and steroid pulses. Patient and graft survival was 100% and 91%, respectively, at 12 months mean follow-up. In the FK506 conv ersion group, two teenage girls with intractable acne and hirsutism we re converted with complete resolution and no change in renal function. Four patients were converted for acute rejection: two who did not res pond to steroid pulse and two who did not respond to both steroids and OKT3. All four grafts were salvaged (mean follow-up, 12 months; mean Creatinine [Cr], 1.1). Three patients were converted for biopsy-proven chronic rejection at 3, 10, and 12 years after transplant (mean Cr, 2 .4) with two of three of patients stable with functioning grafts at 1 year after-conversion. Complications of FK506 therapy included tempora ry insulin-dependent diabetes mellitus (10%), neurological complicatio ns (25%), renal toxicity (15%), and hypertension (85%). There were no cases of gastrointestinal toxicity, hepatic dysfunction, lymphoprolife rative disorders, or life threatening viral infection. All symptoms of toxicity responded to dose adjustment. No patient required conversion from FK506 to other agents. Conclusion: This early experience indicat es that FK506 in combination with low-dose steroids and azathioprine a ppears to provide safe and effective immunosuppression in the pediatri c age group as a primary agent and may salvage grafts in patients with refractory steroid and OKT3 resistant rejection. Graft and patient su rvival is comparable to that seen with conventional cyclosporine-based immunosuppression. Copyright (C) 1997 by W.B. Saunders Company.