MEDICAL RESEARCH COUNCIL TRIAL OF ANTILYMPHOCYTE GLOBULIN IN RENAL TRANSPLANTATION

Abstract

Patients (173) who received live donor or cadaveric primary or secondary renal transplants at 5 British [UK] hospitals were entered into a randomized double-blind controlled clinical trial of equine antilymphocyte globulin (ALG), administered prophylactically to prevent rejection. The ALG was prepared in the early 1970s and used cultured human lymphoblasts as antigen. Following transplantation all patients were treated with a standard immunosuppressant regimen of steroids and azathioprine, and were given either 30 mg/kg ALG or placebo daily for 10 days by i.v. infusion. In comparison with more recently produced materials, the ALG used in this study was of moderate potency in prolonging skin graft survival in monkeys. Primary graft failure occurred in 27 patients (15/86 ALG and 12/87 placebo). At 3 to 5 yr after transplantation 50 of the remaining patients had died, almost all from diseases relating to their renal condition, and 25 more had suffered complete graft failure. No significant differences were found between patients treated with ALG and placebo in the numbers with functioning grafts during the 3 yr following transplantation, in the time between transplantation and the 1st rejection episode, or in the number of episodes during the first 6 mo. after transplantation. This applied whether live or cadaveric grafts were employed. Within the first 6 mo. of operation, infection was given as a major contributory cause of death in 12 patients treated with ALG and in 5 who received placebo (P > 0.1). Infections were also slightly more common during the 2 wk following transplantation in those receiving ALG (13/86 ALG, 10/87 placebo). Graft survival was significantly better in patients who received live donor grafts (P = 0.001) and in patients with the lest donor-recipient histocompatibility mismatches (P = 0.008). No therapeutic benefit to renal graft recipients from the administration of ALG was observed. The risks of fatal infection may have been aggravated. Use of such equine ALG in similar dose regimens is not justified in renal transplantation, especially if some part of the apparent effects on fatal infections is real. These findings are relevant only to the equine ALG used in this study, which was raised with cultured human lymphoblasts as the antigen, and to ALG prepared in a similar way and of similar potency. It should not be inferred that these results are applicable to ALG prepared in other ways.