Acute steroid-resistant rejection episodes in kidney allograft recipients require treatment with antilymphocyte antibodies. Monoclonal anti-CD3 and polyclonal antilymphocyte antibodies have been widely used but seldom compared. Recent data have suggested that these antibodies could be used at reduced doses without jeopardizing their efficacy. In this study, we randomized renal transplant recipients who encountered a first acute steroid-resistant rejection episode to low-dose ATG or low-dose OKT3 treatment. Sixty patients were enrolled in the study. They received prophylactic immunosuppression with cyclosporin, azathioprine, and prednisolone. Treatment of biopsy-proven rejection consisted of a 10-day course of either ATG (n = 31) or OKT3 (n = 29). The total ATG dose was 484 +/- 110 mg, i.e., 0.75 mg/kg per day. The total OKT3 dose was 32 +/- 4 mg, i.e., 0.05 mg/kg per day. We compared reversion of rejection, side effects, immunodepression, and graft function. Reversion of rejection was similar in the two groups, although we noted a trend in favor of ATG. Results were 3% vs 10% early graft failures, 13% vs 23% overall graft failures, 28% vs 38% 3-month actuarial incidence of rebound rejection, and 89% vs 81% 1-year graft survival rate in the ATG and OKT3 groups, respectively. Tolerance was worse in the OKT3 group due to the first-dose syndrome. Infections and cancers occurred with the same frequency. ATG resulted in a deeper and longer decrease in peripheral lymphocyte subsets. Graft function was similar in the two groups. We conclude that low-dose ATG and low-dose OKT3 are equally effective in reversing steroid-resistant acute rejection. Tolerance was better with ATG, which also gave a more potent and longlasting immunodepression. The use of reduced doses of ATG and OKT3 did not appear to lessen their efficacy.

In general nephrology, HCV infection has been associated with type I membranoproliferative glomerulonephritis (MPGN type I) associated with cryoglobulinaemia. In a cohort of 399 renal transplantation (RT) recipients, 117 of whom (29%) were HCV-positive, we selected all patients diagnosed as having membranous GN or type I MPGN by graft biopsy. The prevalence of MGN was 16/399 (4%) with three recurrences, and 13 de novo cases. Only 5/16 (31%) were HCV+, not different from the general RT population. Five patients had an outcome of graft failure after 43 months. Conversely, there were 15 cases of type I MPGN (two recurrences, 13 de novo) but with eight HCV+ recipients (53%, P = 0.02). Considering only the French patients, prevalence was 44% vs 12% in the French RT population (P = 0.006). Eight patients had graft rejection after 59 months (five HCV+). In this type I MPGN subgroup, there were two positive cryoglobulins, two rheumatoid factors and four hypocomplementaemias. In conclusion, there is a clear association between HCV infection and the occurrence of type I MPGN in the allograft in renal transplantation, with terminal renal failure as an outcome.

We conclude that ATG induction is beneficial for all sensitized patients, regardless of their level of sensitization, with regard to acute rejection episodes, graft survival and graft function. Low-dose ATG is sufficient and prevents additional complications.

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