Unintended Consequences of the New National Kidney Allocation Policy in the United States (original) (raw)
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American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons, 2014
Multi-center kidney paired donation (KPD) is an exciting new transplant option that has not yet approached its full potential. One barrier to progress is accurate virtual crossmatching for KPD waitlists with many highly sensitized patients. Virtual crossmatch results from a large multi-center consortium, the National Kidney Registry (NKR), were analyzed to determine the effectiveness of flexible center-specific criteria for virtual crossmatching. Approximately two-thirds of the patients on the NKR waitlist are highly sensitized (>80% CPRA). These patients have antibodies against HLA-A (63%), HLA-B (66%), HLA-C (41%), HLA-DRB1 (60%), HLA-DRB3/4/5 (18-22%), HLA-DQB1 (54%) and HLA-DPB1 (26%). With donors typed for these loci before activation, 91% of virtual crossmatches accurately predicted an acceptable cell-based donor crossmatch. Failed virtual crossmatches were attributed to equivocal virtual crossmatches (46%), changes in HLA antibodies (21%), antibodies against HLA-DQA (6%), ...
A critical appraisal of HLA matching in today’s renal transplantation
Transplantation Reviews, 2004
The increased graft survival obtained with poorly matched kidney grafts is for many clinicians a reason to reconsider the value of HLA matching in today's renal transplantation. Although many other parameters are important, there are still arguments to continue selection of donors on the basis of HLA compatibility with the recipient. Even with the current, very efficient immunosuppression, fully HLA matched combinations have a significantly better graft survival. Furthermore, antibody formation during graft rejection is directly related to the number of mismatched HLA epitopes on the donor organ. HLA matching will prevent that retransplant candidates become highly sensitized, and the incidence of skin cancer after transplantation is significantly lower in HLA matched combinations. Finally, it is to be expected that the threshold to taper or stop the immunosuppression will be lower in HLA matched combinations. As long as the induction of clinical transplantation tolerance is not a routine procedure, a significant proportion of the patients will benefit from a fully HLA matched kidney donor.
American Journal of Transplantation, 2017
De novo donor-specific HLA antibodies (dnDSA) are recognized as a risk factor for premature allograft failure. Determinants of DSA specificity are generated via the indirect allorecognition pathway. Here, we present supportive data for the relevance of predicted indirectly recognizable HLA epitopes (PIRCHE) to predict dnDSA following kidney transplantation. A total of 2787 consecutive kidney transplants performed between 1995 and 2015 without preformed DSA have been analyzed. De novo DSA were detected by single antigen bead assay. HLA epitope mismatches were determined by the HLAMatchmaker and PIRCHE approach and correlated in uniand multivariate analyses with 10-year allograft survival and incidence of dnDSA. The PIRCHE-II score moderately predicted allograft survival. However, the predictive value of elevated PIRCHE-II scores >9 for the incidence of dnDSA was statistically significant (p < 0.001). In a multivariate Cox regression analysis adjusted for antigen mismatch and HLAMatchmaker epitopes, the PIRCHE-II score could be identified as an independent risk factor for dnDSA. The PIRCHE-II score independently from the antigen mismatch and HLAMatchmaker epitopes could be revealed as being a strong predictor for dnDSA. PIRCHE may help to identify acceptable mismatches with decreased risk of dnDSA and thus improve long-term renal allograft survival.
Central Asian Journal of Medical Sciences
Objectives: A successful outcome of renal transplantation depends on various components, with one primary factor being donor and recipient ABO and human leukocyte antigen (HLA) compatibility. The primary aim of our investigation was to determine the impact of HLA-A-B-DR matching on overall and five-year graft and patient survival and to evaluate and improve kidney transplant outcomes. Methods: A total of 70 adult, immunologically low-risk, first-transplant recipients were enrolled in our retrospective study. HLA-A-B-DR typing was performed by the polymerase chain reaction sequence specific primer (PCR-SSP) method. Results: HLA compatibility was carefully matched before transplantation resulting in 81.4% renal transplants with 0-3 HLA mismatches (MM). Overall graft and patient survivals were 52 (74.3%) and 60 (85.7%), respectively, in 70 cases. Five-year graft and patient survivals were 23 (67.6%) and 29 (85.3%), respectively, in 34 cases. A significantly higher rate of graft and pat...
Preexisting Donor-Specific HLA Antibodies Predict Outcome in Kidney Transplantation
Journal of the American Society of Nephrology, 2010
The clinical importance of preexisting HLA antibodies at the time of transplantation, identified by contemporary techniques, is not well understood. We conducted an observational study analyzing the association between preexisting donor-specific HLA antibodies (HLA-DSA) and incidence of acute antibody-mediated rejection (AMR) and survival of patients and grafts among 402 consecutive deceaseddonor kidney transplant recipients. We detected HLA-DSA using Luminex single-antigen assays on the peak reactive and current sera. All patients had a negative lymphocytotoxic cross-match test on the day of transplantation. We found that 8-year graft survival was significantly worse (61%) among patients with preexisting HLA-DSA compared with both sensitized patients without HLA-DSA (93%) and nonsensitized patients (84%). Peak HLA-DSA Luminex mean fluorescence intensity (MFI) predicted AMR better than current HLA-DSA MFI (P ϭ 0.028). As MFI of the highest ranked HLA-DSA detected on peak serum increased, graft survival decreased and the relative risk for AMR increased: Patients with MFI Ͼ6000 had Ͼ100-fold higher risk for AMR than patients with MFI Ͻ465 (relative risk 113; 95% confidence interval 31 to 414). The presence of HLA-DSA did not associate with patient survival. In conclusion, the risk for both AMR and graft loss directly correlates with peak HLA-DSA strength. Quantification of HLA antibodies allows stratification of immunologic risk, which should help guide selection of acceptable grafts for sensitized patients.
Transplant International, 2004
HLAMatchmaker-based strategy to identify acceptable HLA class I mismatches for highly sensitized kidney transplant candidates Abstract HLAMatchmaker determines HLA compatibility at the level of polymorphic amino acid triplets in antibody-accessible sequence positions. Recent studies have shown that among HLA-DR-matched kidney transplants, the HLA-A,B antigen mismatches which are compatible at the triplet level have almost identical graft survival rates as the zero-HLA-A,B antigen mismatches. This finding provides the basis of a new strategy to identify HLA-mismatched organs that have similar success rates as the zero-HLA-antigen mismatches. This report describes how in conjunction with the Acceptable Mismatch program in Eurotransplant, HLA-Matchmaker can expand the pool of potential donors for highly sensitized patients, for whom it is very difficult to find a compatible transplant. Sera from 35 highly sensitized kidney transplant candidates with an average PRA of 96% were screened by lymphocytotoxicity with HLAtyped panels that included cells that were selectively mismatched for one or two HLA antigens for each patient. Acceptable and unacceptable HLA-A,B antigen mismatches were determined from the serum reactivity with the cell panel. HLAMatchmaker analysis was applied to identify additional HLA class I antigens that were matched at the triplet level. For each patient, we donors with acceptable HLA mismatches and could alleviate the problem of accumulation of highly sensitized patients on the transplant waiting list. Keywords HLAMatchmaker. HLA antigen. Triplet. Kidney transplantation. Compatible organ donor