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Sixteen kidney transplant recipients received the IgG2a anti-CD3 monoclonal antibody OKT3 and azathioprine as rejection prophylaxis during the first two postoperative weeks. Concomitant immunosuppression consisted of low dose steroids while cyclosporine A therapy was instituted on day 12. Side effects included fever, bronchospasm, hypotension and diarrhoea. OKT3 caused T cell modulation resulting in CD3 dim+, CD4+ or CD8+, CD5+, WT31- and 11F2- cells. Anti-OKT3 antibodies were found in approximately 50% of the patients. The protocol induced a 100% patient and graft survival and a 81% actuarial freedom of rejection at 18 months. It prevented CsA associated nephrotoxicity in the direct postoperative phase. These beneficial effects outweighed the side effects of OKT3.

1. The realization of the two main goals of the Eurotransplant Organization have been enhanced during the period between 1981 and 1985 by two factors: A reliable HLA-A, -B and -DR typing of kidney donors and recipients, reflected in this analysis by the Hardy-Weinberg analysis but also by the results of the regular tissue typing quality controls. The number of patients who received a kidney without HLA-DR mismatches was 53% (N = 2,904). A significant difference with the 390 of 5,535 (7%) patients who received a kidney with two HLA-DR mismatches. 2. Treatment with cyclosporine increases kidney graft survival significantly in recipients of a first cadaveric transplant which is in agreement with the results of many other groups. Also a significant improvement in kidney graft survival with cyclosporine treatment was observed in recipients of a cadaveric retransplant, an observation in contrast with those of UCLA. 3. Although no significant influence of HLA-A and -B matching was observed in patients treated with or without cyclosporine, the best matched patients had the best graft survival. As stated many times before, the beneficial effect of HLA-A and -B matching is best demonstrated four or five years posttransplantation. 4. The effect of HLA-DR matching on kidney graft survival is highly significant, regardless of whether cyclosporine has been used or not. This finding is also in accordance with those of other investigators. 5. Prolonged cold ischemia periods in cyclosporine-treated patients resulted in a significant decrease of kidney graft survival. This is in contrast with the observations in non-cyclosporine-treated recipients.(ABSTRACT TRUNCATED AT 250 WORDS)

The effect of the presence or absence in the donor of HLA-DRw6 on the survival of renal allografts was studied in 759 HLA-DRw6-negative recipients. The definition of HLA-DRw6 was consistent throughout the study period. 578 patients received an allograft with one HLA-DR mismatch and 181 an allograft with two HLA-DR mismatches. Allograft survival at 1 year was significantly better when the donors were HLA-DRw6-positive than when they were HLA-DRw6-negative, for both one-DR-mismatched (86% vs 65%) and two-DR-mismatched (85% vs 59%) allografts.

A retrospective study was initiated to investigate the influence of recipients' Lewis subtype and HLA-matching on cadaveric kidney graft outcome. A total of 1111 patients receiving a first cadaveric kidney graft were analyzed. No difference in one-year graft survival was found between Lewis-negative (73%, n = 133) and Lewis-positive (73%, n = 978) recipients. Further subdivision of the study group into HLA-A,-B well-matched (0 or 1 mismatches [MM]) and poorly matched (2, 3, or 4 MM) revealed a strong deleterious effect of HLA-A,-B mismatching in the Lewis-negative group only. One year graft survival in Lewis-negative HLA-A,-B poorly matched (2, 3, or 4 A,B MM) patients was 60% (n = 67) versus 86% (n = 66) in the Lewis-negative HLA-A,-B well-matched (0 or 1 A,B MM) group (P = 0.004). For the Lewis-positive group the one-year graft survival rates were 72% (2, 3, or 4 A,B MM; n = 498) and 74% (0 or 1 A,B MM; n = 480), respectively (P = n.s.). The additional beneficial effect of HLA-DR matching again turned out to be strongest in the Lewis-negative group. In Lewis-negative, HLA-DR (0 MM) and -A,-B well-matched recipients (n = 36) graft survival was 94% versus only 64% in the Lewis-negative, DR matched, A,-B mismatched (2, 3, or 4 A,B MM) group (n = 25; P = 0.09). In the Lewis-positive, HLA-DR 0 mismatched group the one-year survival rates were 78% (0 or 1 A,B MM; n = 240) and 73% (2, 3, or 4 A,B MM; n = 253), respectively (P = 0.05). Our data suggest that donor recipient selection should not be based on Lewis matching per se. However, since Lewis-negative patients are at high risk of graft failure when receiving HLA mismatched kidneys, they should preferentially receive optimally HLA matched grafts.

The influence of the cytomegalovirus (CMV) serostatus of blood and kidney donors on patient and graft survival was studied prospectively in 73 cadaveric renal graft recipients. Six out of 12 (50%) CMV seronegative recipients receiving a kidney from a CMV seropositive donor developed CMV disease, in contrast to none of 7 CMV seronegative donor/recipient combinations. Transmission of CMV with blood products to seronegative recipients was not observed in this study. A poor graft survival of 41% 3 years after transplantation was found in CMV seronegative recipients with CMV seropositive allograft donors, compared with an actuarial 3 year graft survival of 72% in the 7 CMV seronegative donor/recipient combinations. Six patients with graft failure had a CMV infection. This study, in accordance with other studies, suggests that selection of CMV seronegative renal allograft donors for CMV seronegative recipients will improve graft survival.

The main purpose of Eurotransplant, an international organ exchange organisation, is to maximize the survival time of transplanted organs through tissue typing and matching. Regular proficiency testings are necessary to assess the reproducibility and the reliability of the HLA typings performed by the individual typing centres. Two different protocols have been used: 1) since 1978, 35 samples of blood and donor spleen were used for cell exchanges (CE) and typed by all participating laboratories; 2) since 1977 samples of donor spleen have been shipped to the reference laboratory in Leiden for retyping (RD) resulting in over 2600 comparable HLA typings. The discrepancy rates of the HLA-A, B, C and DR specificities were analysed over the years. A large number of discrepancies was due to false negative assignments which led to assumed homozygosity at one or more HLA-loci. The recognition of HLA-DR has improved dramatically but with much variation per DR specificity. The concordancy rates for HLA-AB + DR have improved from 40% in 1981 to 91% for CE and 80% for RD typings in 1984. The reproducibility of DR typings in individual laboratories also has improved greatly but there is still considerable variation between the different laboratories.

HLA-DRw6-positive patients are "high responders" to certain renal allograft antigens. A study was therefore conducted of the outcome of 247 first renal allografts in 74 DRw6-positive and 173 DRw6-negative recipients. The effectiveness of matching for HLA-DR determinants in both groups was also analysed. The one-year graft survival in DRw6-positive patients was 59% as compared with 75% in DRw6-negative recipients (p = 0.012). A striking difference between the two groups was that HLA-DR matching significantly improved renal allograft survival only in the DRw6-positive patients. In those patients the one-year survival of HLA-DR-identical grafts was 95% as compared with only 38% for 2-DR mismatched grafts (p = 0.009). In DRw6-negative patients only a slight beneficial effect of HLA-DR matching was observed (83% versus 72% at one year for the 0-DR and 2-DR mismatched grafts, respectively) (p greater than 0.05). These findings are clear evidence that DRw6-positive patients (about a quarter of the patients on the waiting list of Eurotransplant) should be given HLA-DR-identical kidney transplants only.

Results in this study demonstrate that HLA matching has a beneficial effect on the survival of renal allograft in pediatric recipients. The introduction of a child-match procedure may have led to a lower degree of HLA well-matched grafts because of the small size of the pediatric waiting list. The poor results obtained in the group of children aged less than 6 years may have been due to a difference in physical condition at the moment of transplantation. This may explain why 4 of 20 (20%) of the failures in that age-group were due to patient death. The best results with the child-match procedure were obtained if the donor and recipient were both aged between 6 and 15 years. The overall graft survival in all children was improved by the use of Cs. An increase of approximately 10% was observed in this group of patients. The numbers in this group are too small, however, to permit any meaningful analysis of the influence of Cs on HLA matching. Finally, the overall results in this report demonstrate that renal transplantation is an effective form of therapy for end-stage renal disease in children.

In a consecutive series of 146 kidney transplant recipients treated with cyclosporin A a strong correlation between matching for the HLA-A, HLA-B, and HLA-DR loci specificities and outcome of the grafts was observed in male recipients with non-O blood groups. Such a beneficial effect of matching was not found in female patients or male patients with blood group O. In these patients survival of the grafts at one year was good irrespective of the number of HLA-A, B, and DR mismatches. Also in 47 male heart transplant recipients immune responsiveness against mismatched HLA antigens was related to blood group. A significantly higher incidence of rejection episodes was observed in male patients with non-O blood groups (n = 32) than in those with blood group O (n = 15). Matching for HLA-DR reduced the number of acute rejection episodes in male patients with non-O blood. These findings may help explain the controversial reports about the importance of HLA matching in organ transplantation. Furthermore, as most candidates for heart transplantation are male and not of blood group O, the higher incidence of graft rejection in these patients underscores the need for an exchange strategy of donor hearts.