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We attempted cessation of prednisone therapy in 16 pediatric renal allograft recipients who were between the ages of 3 1/2 and 16 years at the time of transplantation. Fourteen had primary grafts and 2 had second grafts. Nine had cadaver and 7 had living-related donor grafts. At the time of cessation of prednisone, cyclosporine was the only other immunosuppressive therapy for 15 of the patients and 1 patient was receiving CsA and azathioprine. All the patients had stable serum creatinines at the time prednisone was stopped, between 7 months and 5 years posttransplantation. Seven patients have had no episodes of rejection, continuing to receive CsA as their only immunosuppressive therapy and have stable renal function between 16 months and 3 1/2 years (mean: 2 years) after stopping prednisone. Stopping the small maintenance dose of prednisone resulted in improved growth in patients whose epiphyses were not fused. They improved their weight:height ratios and lost their cushingoid appearance. Serum cholesterol levels declined significantly. Patients who required antihypertensive drugs to control their blood pressure while receiving prednisone required fewer or no drugs when off prednisone. Nine patients had acute rejection episodes and were put back on maintenance prednisone following a 3-day steroid pulse. All these patients had a prompt improvement in renal function following the steroid pulse. However, only 3 stabilized function at preprotocol baseline Scr. Four currently have functioning grafts with Scr greater than the preprotocol Scr. Two patients have returned to dialysis. Although stopping steroids is a worthy goal in pediatric renal allograft recipients, we cannot recommend this strategy as routine management because of the 56% rate of acute rejection episodes in the patients who had prednisone withdrawn.

Eleven renal transplant patients between the ages of 4 and 19 years, on a single daily oral dose of cyclosporine (CsA) and either a low oral dose or no dose of prednisone, had venous blood drawn at periodic intervals throughout a 24-hour period. CsA levels were measured by whole blood radioimmunoassay. All the patients had similar patterns of CsA pharmacokinetics with a single peak blood level at two to eight hours after the drug was given. Plasmas separated from the bloods at 37 degrees C were added to third party mixed lymphocyte reactions (MLR). The kinetics of suppression of the MLR by serial plasmas did not follow the CsA levels. Instead, we observed patterns of suppression similar to those that have been described in adults. Five patients had pattern I with two peaks of plasma-mediated MLR suppression, and had no rejection episodes. Two of the patients had pattern II with only one peak of MLR suppression, and both had episodes of acute rejection. One patient showed pattern III with a pleateau of MLR suppression, and has had no rejection episodes and no obvious CsA toxicity. Three patients showed pattern IV with a continuously low level of plasma-mediated MLR suppression throughout the day, and two of them have had severe rejection episodes. Immunopharmacodynamic profiling (IP) may prove to be useful in individualizing therapeutic regimens for patients with renal allografts treated with CsA.