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We examined the graft survival of 12,883 first unrelated kidney grafts from nonliving donors, transplanted between 1 January 1971 and 31 December 1987 within 52 renal transplantation centers participating in the Eurotransplant organization. The 5-year graft survival increased from 38.8% for the period 1971-1975 to 66.0% for the period 1981-1987 for patients treated with cyclosporine, whereas the half-life increased by only 2 years, from 9.7 years to 11.6 years over the same period, based on grafts functioning at 1 year posttransplantation. Results per HLA locus showed considerable improvements within mismatch groups over the entire period. Large differences between mismatch groups for the early years were observed, but within the cyclosporine era only HLA-B showed a statistically significant difference in half-lives (13.2 versus 9.0 years, for 0 and 2 mismatches respectively, P = 0.013). When other prognostic factors were taken into account, it was revealed by means of an exponential model that number of HLA-B mismatches, donor and recipient age and sex, and recipient diagnosis of diabetes had significant effects on the long-term outcome of the grafts. Depending on the combination of these parameters, estimates of half-life varied from 4.9 to 14.5 years. These results show that matching for HLA-B is still of benefit in the longer term and that other prognostic factors play an important role in predicting the late outcome of renal allografts.

The effect of matching for the HLA antigens has been well established as important in the prognosis of kidney grafts. By analyzing the effect of matching on first transplants from unrelated donors in specific intervals up to 3 years posttransplantation, we show that the effect of HLA-DR matching is strongest in the first 5 months following transplantation (relative risks of graft failure 1.31 and 1.77 for 1 and 2 HLA-DR mismatches, respectively, compared with no mismatches). For patients whose grafts remained functioning after 5 months, there was no significant further improvement in graft survival to 3 years (relative risks 1.16 and 0.98 for 1 and 2 HLA-DR mismatches, respectively, compared with no mismatches)--i.e., the gain in graft survival by matching for HLA-DR appears to be due to its influence in the first 5 months following transplantation. For HLA-B, the matching effect was evident both before and after 5 months (relative risks 1.11 and 1.27 for 1 and 2 HLA-B mismatches, respectively, compared with no mismatches and modelled as constant over the 3-year period), whereas no effect of HLA-A matching was evident in the period up to 3 years.

Data from 7436 cases of first-cadaver transplants between 1981 and 1986 from 50 transplant follow-up centers within Eurotransplant, were analyzed with respect to the effect of HLA-DR matching on graft prognosis within the first year posttransplant. The use of cyclosporine was allowed for as well as the variation in graft survival rate between transplant follow-up centers. After adjustment for these variables, HLA-DR matching was still very significant. The effect of CsA on graft survival varied between centers--i.e., interaction was observed--but the effect of HLA-DR mismatching did not vary significantly between centers. Over all the centers there was a 1.4-fold increase in relative risk for each increase in HLA-DR mismatch, corresponding to predicted one-year graft survivals of 86.5%, 81.9%, and 75.4% for 0, 1, and 2 HLA-DR mismatches respectively, in patients receiving CsA, and 72.5%, 64.2%, and 53.6% in patients not receiving CsA.

First cadaver, unrelated kidney graft survival at one year from 50 Eurotransplant centers was analyzed and found to show marked changes in survival rates over the 20-year period from 1967 to 1986 inclusive. Full information on HLA-A, -B, and -DR matching and use of cyclosporine therapy was only available for the period 1981 to 1986. When these factors were allowed for, the number (and type) of HLA mismatches was shown to have a significant and independent effect on differences in survival rates whereas the effect of cyclosporine differed over the different years.