A prospective, randomized trial of FK‐506 in renal transplantation ‐ A comparison between double and triple‐drug therapy
Authors: Shapiro Ron , Jordan Mark , Scantlebury Velma , Vivas Carlos , Fung John , McCauley Jerry , Tzakis Andreas , Randhawa Parmjeet , Demetris A. J. , Irish William , Mitchell Sandi , Jensen Christopher , Jain Ashok , Hakala Thomas R. , Simmons Richard L. , Starzl Thomas E. 
Published: September 2024

Previous clinical evaluation of FK506 in renal transplantation has demonstrated equivalent patient and graft survival when compared with cyclosporine‐based regimens. However, lower steroid and anti‐hypertensive medication requirements and lower serum cholesterol levels have been seen in patients receiving FK506. In August, 1991, a prospective, randomized trial was begun, comparing FK506/prednisone with FK506/azathioprine/prednisone. Two‐hundred‐and‐four adults were entered into this trial between August 1, 1991, and October 11, 1992. The mean recipient age was 43.8±13.7 years, with a range of 17.6‐78.0 years. Sixty‐one (30%) recipients received a 2nd, 3rd or 4th transplant, while 35 (17%) had a PRA greater than 40% at the time of transplant. Thirty‐three (16%) of the transplants were in recipients over 60 years of age, Thirteen percent of the kidneys were from living donors; 13% of the cadaveric kidneys were from pediatric donors less than 3 years of age and were transplanted en bloc. The mean cold ischemia time was 31.4+8.4 hours, and the mean donor age was 34±2.10 years, with a range from 4 months to 75 years. With a mean follow‐up of 9±4 months, the 1‐year actuarial patient survival is 93%; for the two‐drug group it is 95%, and for the three‐drug group it is 91% (p = NS). One‐year actuarial graft survival is 86%; in the two‐drug group it is 90%, while in the three‐drug group it is 82% (p = NS). The mean serum creatinine and BUN are 1.85±0.76 mg/dl and 30+ 14 mg/dl; the values are not significantly different between the twoand three‐drug groups. Rejection was seen in 45% of patients, 51% in the two‐drug and 39% in the three‐drug group (p=0.09). In cadaveric recipients, more rejection was seen in the two‐drug group (58%) than in the three‐drug group (39%; p<0.02: 24 (12%) of patients required OKT3 or ATGAM® for rejection: 24 (12%) had cytomegalovirus; an equal incidence was seen in both groups. New onset diabetes was seen in 14% of patients; there was a higher incidence in the two‐drug (20%) than in the three‐drug (8%) group (p<0.03). The incidence of PTLD was 1% (2 patients). Crossover between the two limbs was seen commonly: 26 /25%) of the patients in the two‐drug group required the addition of azathioprine, while 46 (45%) of the patients in the three‐drug group required discontinuation of azathioprine (usually because of a falling white blood cell count or hepatic dysfunction). Sixty‐five (32%) patients are off steroids, while 88 (43%) patients are not taking any antihypertensive medications. The mean serum cholesterol is 193 53 mg/dl. These data confirm earlier reports about the efficacy of FK506 in renal transplantation. The benefit of azathioprine is unclear, with no improvement in patient and graft survival and a higher crossover rate, but with less rejection in certain subgroups and less diabetes.