The use of cyclosporin A and prednisone in cadaver kidney transplantation

Abstract

Eighteen patients were treated with primary cadaveric renal transplantation using cyclosporin A therapy, and four more patients undersent cadaveric retransplantation. Eleven of the 22 recipients were conditioned with lymphoid depletion before transplantation, using thoracic duct drainage or lymphapheresis for two to eight and one-half weeks. Cyclosporin A was begun a few hours before grafting. The other 11 patients were pretreated with cyclosporin A for from one day to 18 days. After transplantation, the majority of patients in both subgroups of 11 had rejection develop, but in most, the immunologic process was readily controlled with relatively small dosages of prednisone. After follow-up periods of two to four and one-half months, one patient has died of the complications of a coronary artery reconstruction that was not related to the transplantation. Another graft was lost from rejection, and a third organ was removed because of ureteral necrosis. Nineteen of the original 22 cadaveric kidneys are functioning, including 17 of the 18 kidneys given to patients who were undergoing transplantation for the first time. The only loss in the latter group of 18 patients was in the patient who died after an open heart operation. Results of these studies have shown that cyclosporin A is a superior and safe immunosuppressive drug but that, for optimal use in cadaveric transplantation, it usually should not be given alone. Steroid therapy greatly amplified the value of cyclosporin A. Unless major delayed morbidity develops which is not obvious so far, this drug combination should permit revolutionary advances in the transplantation of all organs. Other adjuncts to the cyclosporin A-steroid combination, including lymphoid depletion techniques, will require further investigation.

Fig. 1

A typical example of post-transplantation oliguria which became most severe on day 4 in Patient 7. Cyclosporin A in daily doses of 17.5 milligrams per kilogram was begun one day before transplantation. With the apparent rejection, there was progressive graft swelling, pain and tenderness. These findings as well as low grade fever and oliguria were relieved promptly by a single bolus of methylprednisolone given intravenously. Nine days later, maintenance dosages of prednisone were started orally.

Fig. 2

The course of Patient 5 whose first cadaveric transplant in 1977 was rejected after 21 days. A second transplant was also rejected with azathioprine and prednisone therapy despite 30 days pretreatment with thoracic duct drainage. A third transplant was performed 50 days after the unsuccessful second transplantation. The patient was switched from azathioprine to cyc1osporin A at that time, prednisone was stopped and thoracic duct drainage was discontinued two days later after a total of 82 days. See text for discussion. D, Dialysis; MP, methylprednisolone, 1 gram intravenously.

Fig. 3

Use of a short course of orally administered prednisone leading within five to seven days to maintenance therapy with 10 to 20 milligrams per day. This use of prednisone has been referred to as minicycle therapy. The daily dose of cyclosporin A was always 17.5 milligrams per kilogram.

Fig. 4

Courses of Patient 3, top, and Patient 2, bottom, show acute rejection 38 and 45 days, respectively, after transplantation. No significant changes in urine output, body weight or temperature were recorded. Doses of cyclosporin A were 17.5 milligrams per kilogram per day throughout. Renal scans always revealed good flow, but there was decreased Hippuran, sodium o-iodohippurate, clearance before, during and after the aforementioned episodes. Note the declines in creatinine level after institution of low dosages of prednisone.

Fig. 5

An example of cyclosporin A nephrotoxicity is shown in the course of Patient 4. The cyclosporin A dosage was al first increased with resulting rises in the creatinine and blood urea nitrogen levels. Note that both measures returned toward normal within a few days after reducing cyclosporin A dose to 9 milligrams per kilogram per day. The prednisone dose was kept at 15 milligrams per day throughout the time shown.