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Background: BK polyomavirus infection (BKVi) is an important cause of kidney transplant (KT) loss, but there is scarce evidence on the impact of BK plasma viral load on graft function and long-term KT survival., Methods: A retrospective cohort study including all KT recipients with BKVi (BK viremia identified in ≥3 consecutive samples by polymerase chain reaction) in our center from January 2010 to December 2020 was performed. A case-control study (1:2) was performed. We grouped the cases according to their highest peak viral load: low-level viremia (<10,000 copies/mL) and high-level viremia (≥10,000 copies/mL). To identify risk factors for BKVi, a logistic regression analysis was achieved, and a multivariable Cox regression was used to describe risk factors for graft loss., Results: A total of 849 KTs were performed, and 67 presented BKVi (low-level viremia, n = 35 and high-level viremia, n = 26). In logistic regression analysis male sex (odds ratio [OR], 4.226; 95% CI, 1.660-10.758, P = .002), age (OR, 1.047; 95% CI, 1.008-1.088; P = .018), and retransplant (OR, 4.162; 95% CI, 1.018-17.015; P = .047) were predictors of BKVi. Acute rejection was more frequent in the BKVi group (18% vs 4.9%, P = .004), and graft survival was lower in patients with BKVi and high-level viremia (P = .027). In Cox regression analysis, BKVi (hazard ratio, 3.657; 95% CI, 1.146-11.670; P = .029) and specific BKV (BK polyomavirus) high-level viremia (hazard ratio, 1.988; 95% CI, 1.012-3.907; P = .046) were predictors of shorter graft survival., Conclusions: BKV high-level viremia was associated with BKV nephropathy and poorer graft survival. Additionally, acute rejection is more frequent after BKVi. It is necessary to develop strategies safe and effective for these patients., (Copyright © 2022. Published by Elsevier Inc.)

An important contribution of HLA-A antigen matching in renal transplantation was reported initially, hut later publications showed a minor or absent role. We analyzed the contribution of HLA-A locus matching to graft survival in 17,672 first renal transplants from unrelated, nonliving donors. We show that an independent HLA-A matching effect still exists. Due to its relative weakness and late appearance, large numbers and longer follow-up periods are required. The HLA-A matching effect is a significant factor in first renal allograft survival up to 6 years after transplantation, with an increasing effect over time. This is in contrast to the strong, short-lived, effects of HLA-DR and -B matching, which can only be detected up to 6 months and 2 years after transplantation, respectively. A clear additive beneficial effect of HLA-A matching is shown in the group without B and DR mismatches. Therefore, prospective matching for the HLA-A antigens remains important for renal allograft survival.

The observation of elevated levels of HLA class I molecules in sera of HLA-A9-positive individuals, and their potential role in the regulation of the immune response, motivated us to study the effect of the presence of HLA-A9 in either kidney donor or recipient on graft survival. Analysis of data from unrelated first transplants performed within the Eurotransplant area revealed that in the group of patients who were not treated with cyclosporine (n = 2051), transplants with no HLA-DR mismatches in which donors (D) and recipients (R) shared the HLA-A9 antigen (D+R+), had significantly poorer graft survival (P = 0.0001) than all other combinations, reaching a 20% difference at 5 years posttransplantation. This effect, which was not found in the CsA-treated patient group (n = 7297), was specific for HLA-A9. The implications of this findings are discussed in relation to the mechanisms of the alloimmune response.

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.

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.

The histories and present roles of four European Registries are described. Three are transplant sharing organizations, Eurotransplant (ET), Scandiatransplant (ST), and the United Kingdom Transplant Service (UKTS). The Registry of the European Dialysis and Transplant Association is a patient Registry that tracks patients on dialysis as well as after transplantation and follows them from center to center. The transplant organizations collaborate by linking patient records on the EDTA Register. These large central Registries have evolved specialized computer methodologies for recording the follow-up of patients, researching the patient file, and improving the service to centers. The log-rank test is useful for the evaluation of pooled results. Reliability of donor typings can be verified by testing results for the Hardy-Weinberg equilibrium. A method for the prediction of pool size required to find matched recipients is described. Collaborative studies have been carried out in an attempt to discover the factor(s) responsible for the "center effect." New trends in analysis of transplant results will include detailed documentation of rejection episodes. Compliance by centers contributing to the transplant organizations is ensured by the need for organ interchange, whereas the EDTA Registry depends on the directors of centers being motivated by the publication of pooled statistics and results and by the provision of feedback information to the individual units.

Cell-mediated lympholysis (CML) reactivity against the splenocytes of the kidney donor might be a good in vitro correlate of the homograft reaction. The present study was performed in an attempt to determine whether CML nonreactivity between unrelated donor-recipient combinations occur and, if so, under what conditions. We were able to show that CML nonreactivity occurs between unrelated donor-recipient combinations in 70% of the nonrejecting patients, whereas all of the rejecting patients were CML reactive. Patients with CML nonreactivity did clinically well more frequently than those that were CML reactive. The question as to whether or not such variables as HLA-A, B, and DR match and sex, the number of pretransplant blood transfusions, and the degree of presensitization, etc. predispose to the development of donor-specific CML nonreactivity was studied as well. Sex and compatibility for HLA-B antigens between donor and recipient might be such factors.

Since 1981, more and more transplant centres collaborating within the Eurotransplant Organization started to use Cyclosporin-A (CsA) as part of their immunosuppressive protocols. Although these protocols differ from centre to centre it was felt important to study the clinical significance of CsA on renal allograft survival, especially with regard to other relevant but more constant factors such as HLA-A, -B and -DR matching, pretransplant blood transfusions, ischemia times, etc. This study encompasses 3150 transfused kidney transplant recipients of whom 765 have received CsA. Analysis shows that the group of CsA treated patients had a significantly better graft survival as compared to the non-CsA treated patients i.e., 71% versus 62% at 2 years respectively. The best kidney graft survival was obtained in the HLA-DR well matched donor-recipients combinations even when CsA was used (79% at 2 years). A significant adverse effect of prolonged cold ischemia times was observed when CsA was administered.

1. Cyclosporine significantly improved kidney graft survival by 10-15%. 2. Matching for HLA-DR, HLA-B + DR and HLA-A + B + DR improved kidney graft survival significantly in non-CsA-treated patients. 3. Matching for the HLA-A, -B, and -DR loci, apart and in combination, significantly improved kidney graft survival in CsA-treated patients. 4. The best kidney graft survival was observed in HLA-A + B + DR identical combinations treated with CsA (76% at 5 yrs).

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.

Data on the effect of HLA-A and HLA-B matching between unrelated donors and recipients focus mainly on graft survival. After linking the follow-up data of the European Dialysis and Transplant Association and those of the Eurotransplant Foundation, the effect of HLA-A and HLA-B matching on recipient survival could be studied. Recipients of well-matched kidneys--i.e., without mismatches for the HLA-A and B antigens--had 51 per cent graft survival at five years, whereas recipients of grafts mismatched for four antigens had 32 per cent graft survival at five years. The overall P value between the five different mismatch classes was 0.0005. Patient survival at five years was 72 per cent in recipients of a kidney without HLA-A and B mismatches and 54 per cent in recipients of a completely mismatched donor kidney (overall, P = 0.001). These results suggest that matching for the HLA antigens has a beneficial long-term effect not only on renal-allograft survival but also on patient survival.

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.

We think that the determination of acceptable mismatches is an efficient approach to increase the chance of finding a crossmatch-negative donor for highly sensitized patients. This approach has several advantages (4,5) namely: 1. There is no need for distribution of patient sera to other tissue typing centers. 2. Rather than performing crossmatches with all donors, most of which will be positive, selection is based on a predictable negative crossmatch. 3. Selection of potential donors is based on data obtained by the recipient centers, which has all the information concerning the patient's immunological background (transfusion, specific alloantibodies, autoantibodies) rather than on a negative crossmatch at another tissue typing center. 4. Selection is based on HLA-DR compatibility between donor and recipient, which is, both in our and other analyses (6), important for an optimal prognosis of graft survival in highly immunized patients. Of course, there are still patients for whom this protocol is not very helpful (rare HLA-types, hardly any or no acceptable mismatches). For these patients it might be that other approaches, including removal of circulating antibodies (7), may be the only solution.

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.