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In cyclosporine (CsA)-treated renal transplant recipients complete corticosteroid withdrawal followed by CsA monotherapy has been associated with severe rejection episodes in a significant proportion of patients. We report the results of replacement of steroids by azathioprine (AZA) in 25 primary cadaveric renal transplant recipients initially treated with CsA and methylprednisolone (MP). MP taper was started 8.8 +/- 5.6 months posttransplant when the MP dose was either 10 mg/day or 20 mg every other day. MP was tapered off over a 5-month period. At the initiation of MP taper, AZA was added at 1 mg/kg/day and increased to 1.5 mg/kg/day after two months. The CsA dose was adjusted to maintain trough serum levels as measured by radioimmunoassay (RIA) of 50-75 ng/ml, during and after MP withdrawal. Seventeen patients have remained continuously off MP for 14.6 +/- 5.0 months with stable renal function. Reinstitution of MP at 10 mg/day was required in 8 patients, 6 for rejection (1.8 +/- 0.7 months after MP withdrawal), 1 for AZA-induced leukopenia, and 1 for de novo glomerulopathy. Renal function returned to baseline in all 6 patients with rejection after reinstitution of MP. Two of these patients have again been successfully retapered off MP. In the patients withdrawn from MP, body weight and mean arterial blood pressure had decreased by 2.1 +/- 1.3 kg (P less than .05) and 11 +/- 7 mmHg (P less than .05), respectively, at the time of the most recent follow-up compared with values at the initiation of steroid withdrawal. The number of blood pressure medications per patient decreased by 38% (P less than .05) and 6 patients were able to discontinue all antihypertensive drugs after cessation of steroids. Discontinuation of MP also resulted in a decrease in serum cholesterol concentration from 248 +/- 50 to 217 +/- 55 mg/dl (P less than .05). We conclude that steroids can be replaced by AZA in the majority of CsA-treated primary cadaveric renal transplant recipients by the end of the first posttransplant year without an adverse effect on graft survival. This protocol resulted in significant reductions in serum cholesterol, mean arterial blood pressure, and body weight, and may avoid the long-term side effects of steroid therapy.

The use of Cyclosporine (CsA) immediately after renal transplantation may be associated with an increased incidence and duration of acute tubular necrosis (ATN) and permanent primary graft nonfunction. To avoid this potential interaction we treated recipients of primary cadaveric grafts initially with azathioprine (AZA), methylprednisolone (MP), and 5 daily doses of Minnesota antilymphoblast globulin (MAG) (postoperative days 3-7). AZA was discontinued and CsA started on day 6 if the graft was functioning by then. If ATN persisted beyond day 6, AZA and MAG (maximum 12 doses) were continued and CsA withheld until graft function was established (group 1-33 patients). This protocol is compared to our previous regimen of MAG (14 doses over the first 3 weeks), AZA and MP (group 2-68 primary cadaveric graft recipients). Improved one-year graft survival (81% vs. 60%, P less than 0.05) and patient survival (93% vs. 81%, P less than 0.05) were seen in group 1. The incidence and duration of ATN did not differ in the two groups. During the first year after transplantation more patients in group 1 were completely free of rejection episodes (40% vs. 20%, P less than 0.05) and the number of rejection episodes per patient was also lower in this group (1.0 +/- 15 vs. 1.6 +/- 49, P less than 0.05). The incidence of infections was not different in the two groups. No tumors have developed in either group. We conclude that in primary cadaveric renal transplantation the initial administration of a short course of MAG followed by CsA therapy results in excellent graft and patient survival while avoiding the potential adverse effect of CsA on an allograft already subjected to preservation injury.