Low-dose cyclosporine for cadaveric renal transplantation

Low-dose cyclosporine (CsA) plus prednisone for induction and maintenance immunosuppression were used in 106 consecutive cadaveric renal transplants. Previous reports of lower initial CsA have described its use in combination with other forms of immunosuppression. An oral CsA dose of 3 mg/kg was given 2-4 hr before operation, and maintenance CsA was started 12 hr post-operatively at 1 or 1.5 mg/kg i.v. every 12 hr for non-functioning and functioning kidneys, respectively. Oral CsA was given at 3 times the i.v. dose and started 2-3 days postoperatively. The CsA dose was adjusted to maintain plasma trough levels, as measured by radio-immunoassay, of 150-200 ng/ml for the first two weeks, 125-175 ng/ml 2-4 weeks posttransplant, and 100-150 ng/ml for the second month after transplant. Between two and six months, the CsA dose was gradually reduced by 33%. Maintenance prednisone was rapidly reduced 5 mg/month to a maintenance dose of 10 mg/day. Graft survivals for low and high-risk patients at one year were 91% and 81%, respectively. Patient survivals for low-and high-risk patients at one year were 97% and 90%, respectively. Patient death was caused by: aspiration (1), suicide (1), cardiac failure (1), Mediterranean fever with colon perforation (1), and traumatic renal artery disruption (1). Except for death, grafts were lost to primary nonfunction (2), accelerated rejection at +/- 12 hr (3), medical noncompliance (1), renal artery thrombosis (1), and vascular rejection (1). Of 106 patients, 26 (25% were treated for rejection with 3.5 g of i.v. methylprednisolone over 10 days; 25/26 (96%) rejections were reversed with methylprednisolone alone. OKT-3 failed to reverse the remaining vascular rejection. All 9 conversions from CsA to azathioprine for toxicity were successful. Our definition of toxicity was rising serum creatinine, normal CsA level, and no response to 7-10 days of i.v. methylprednisolone and no change in biopsy. We were not able to distinguish CsA toxicity and rejection in most biopsies. Average serum creatinines at 1, 6, and 12 months were 1.6 mg/dl, 1.55 mg/dl and 1.65 mg/dl, respectively. We conclude that low-dose CsA plus prednisone can be successfully used for all cadaveric renal transplants without other forms of immunosuppression. Steroid-resistant rejection is extremely rare if adequate time is given for i.v. methylprednisolone treatment. Almost all "steroid-resistant rejections" were found to be CsA toxicity, and they were reversed after conversion to azathioprine.