Selective (Tacrolimus) FK506 Rescue Therapy Provides Stability for At-Risk Pediatric Renal Transplant Patients

There has been marked improvement in the past decade of graft and patient survival in the pediatric renal transplant population. A major contributor to this success has been improved

immunosuppressive drugs. Approximately one-third of patients continue to have difficulty with recurrent rejections/chronic rejection, allograft nephropathy, or drug toxicity. Thirty-five

pediatric patients have had renal transplantation at the IWK∼Grace Health Centre over the past 5 years. We developed criteria for switching patients from baseline Cyclosporin A (CyA) to

FK506: (1) 2 or more biopsy-proven rejections in less than 3 years, (2) biopsy-proven CyA toxicity, and (3) patient concerns regarding CyA ± non-compliance, (4) significant facial morphology

changes on CyA, and (5) primary diseases aggravated by CyA.

Nine patients have been switched to FK506 during the past 5 years (7 with > 2 rejections on CyA, 2 with CyA toxicity). All patients received induction therapy with monoclonal antibody and

started CyA 5 - 7 mg/kg/day, Azathioprine 1 ½ - 2 mg/kg/day and Prednisone with initial transplantation. All patients remained on a minimum of Prednisone 10 mg/m2 q alternate day as

maintenance. Nine patients fulfilled the criteria for switching. The majority had creatinine clearance (CrCl) data pre and post switch. All patients had renal biopsy at conversion. Baseline

creatinine (Creat) levels one month and one week prior to conversion and Creat levels one month, three months, and twelve months post conversion were assessed.

Three patients had mild deterioration of renal function over the following year with 6 patients showing stable or improved function in this high-risk group. CrCl (ml/sec/1.73 m2) prior to

conversion (mean ± standard deviation) was 0.80 ± 0.25 which was not different from post conversion CrCl of 0.91 ± 0.33 (n=8). Creat (µmol/L) assessments revealed one month pre: 131 ± 31

(n=9); one week pre: 138 ± 41(n=9); one month post: 127 ± 41(n=9); three month post: 133 ± 47 (n=7); and one year post: 134 ± 44 (n=6) for this patient population which demonstrates

stability.

Pediatric renal transplant graft survival has improved in many centres with one year survival rates of > 90%. There has been disappointing long-term survival data. We targeted patients with

evidence of renal allograft deterioration with biopsies to document CyA toxicity and/or CyA failure (> 2 rejections in less than 3 years). Converting this subgroup of patients to FK506

allowed graft stability for the first year. Improved understanding of toxicity and limitation of individual immunosuppression agents should allow better choices for the pediatric renal

transplant population.

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