HLA Points Assigned in Cadaveric Kidney Allocation Should Be Revisited: An Analysis of HLA Class II Molecularly Typed Patients and Donors

The points now assigned for the quality of HLA match have received significant scrutiny to be modified in an effort to help reduce disparity in access to kidneys of minority groups, and since differences in graft survival between groups of patients in each of the HLA matched groups is less now than in the past. We analyzed long-term (5-year) graft survival in 746 DR DNA typed recipients of cadaveric kidneys transplanted from 1994-2001 whose donors were also DR DNA typed, with allocation based on those DNA-based typings. Five-year graft survival was not significantly different for recipient groups irrespective of if they had zero (84%), one (92%), two (89%), or three to four B, DR mismatches (79%) (log-rank = 0.15; died with a functioning graft [DWFG] censored). Mismatching of three and four DR and DQ antigens in black but not white patients was associated with significantly worse survival (Relative Risk = 2.9) (p = 0.002). The incidence of minority transplants in the well-matched group (zero and one B, DR mismatch), 12.8% (20/156) was over half that of the less well-matched group, 27.1% (160/590) (p < 0.001). Our data indicate that the current HLA-B, DR-based point system used to allocate kidneys warrants re-evaluation. Our data, taken in the context of the UNOS data, which has recently been re-evaluated, suggest that the only HLA-DR remain as a component of the national kidney allocation algorithm so as to increase access of kidneys to minorities and minimize graft loss.     

The impact of HLA frequency differences in races on the access to optimally HLA-matched cadaver renal transplants. The Medical Advisory Committee.

We examined the donor/recipient HLA match of 448 consecutive cadaver renal transplants to determine if donor race had an impact on the quality of HLA match that was achieved. Eighty (17.9%) kidneys from black donors and 368 (82.1%) from nonblack donors (87.8% caucasians) were distributed to the blood type compatible and crossmatch negative recipients on the basis of a local variance of the United Network for Organ Sharing (UNOS) point system. There were 278 (62%) nonblack and 170 (38%) black recipients, numbers close to those of nonblacks and blacks on the waiting list (59% and 41%, respectively). Kidneys from nonblack donors represented 86% (240/278) of transplants for nonblack and 75% (128/170) of transplants for black recipients. The best matches, i.e., zero-A,B,DR, zero-A,B, zero-B,DR, and 1-A,B,DR mismatches, for nonblack recipients were solely derived from the nonblack donors, and the few well-matched kidneys from black donors were distributed to black recipients. Black recipients with zero mismatches were few (3, 2%) compared with nonblacks (21, 8%). Kidneys received by black recipients were more likely to be poorly matched (5-6 mismatches) if coming from nonblack donors (57/128, 44%) than black donors (11/42, 26%), P = 0.035. It was also observed from HLA frequency comparisons that well-matched kidneys from nonblack donors were rarely distributed to black patients with HLA phenotypes unique to or more common in blacks who represented a sizeable portion of blacks on the waiting list. We conclude that better donor/recipient HLA matches are achieved when both donors and recipients are of the same race. Thus a larger number of black donors are needed to improve the quality of HLA matching for potential black kidney transplant recipients.     

Multivariate analysis of the effectiveness of using antibody induction therapy according to the degree of HLA mismatches

OBJECTIVE: HLA mismatches have a strong impact on acute rejection and renal allograft survival. The objective of this study was to evaluate the effectiveness of antibody induction according to the degree of HLA mismatches. METHODS: Of 20,429 deceased donor (DD) transplantations and 12,859 living donor (LD) transplantations reported to the United Network for Organ Sharing (UNOS) between 1999 and 2001, 51% of DD and 45% of LD transplant recipients received induction therapy. Propensity scores (PS) were calculated to indicate independent factors associated with the use of induction. Levels of HLA match examined for DD transplant recipients were 0 ABDR (n = 3239), 0 DR (n = 4210), and DR mismatched transplants (n = 12,980), and 0 (n = 1133), 1 (n = 3836), and 2 (n = 7890) haplotype mismatches for LD transplant recipients. Outcome parameters were reported as hazard ratios (HR) for graft loss and odds ratios (OR) for first-year acute rejection. RESULTS: Recipients with HLA mismatches were more likely to receive induction antibody for DR mismatch in DDs (PS = 1.11, 95% confidence interval [CI] 1.04-1.19) and for haplotype mismatch in LDs (PS = 1.36, 95% CI 1.22-1.52). Induction reduced the likelihood of acute rejection for DD transplant recipients regardless of the level of HLA mismatch (OR = 0.70; 95% CI 0.57-0.85 in 0 ABDR MM; OR = 0.76, 95% CI 0.64-0.89 in 0 DR MM; and OR = 0.69, 95% CI 0.62-0.77 in DR MM), and for 2 haplotype mismatched LD transplant recipients (OR = 0.82, 95% CI 0.70-0.96); in other LD transplant recipients, reductions in acute rejection rates were observed but not statistically significant. Induction reduced the risk of graft loss for DR mismatched DD transplant recipients by about 12% (HR = 0.88; 95% CI 0.80-0.97). CONCLUSIONS: Antibody induction resulted in a significant reduction of acute rejection and graft loss for patients with HLA mismatch.     

Evidence that matching for HLA antigens significantly increases transplant survival in 1001 renal transplants performed in the northwest region of England

In the 20-year period from March 1968 to March 1988, 860 patients received 1001 renal transplants in the Northwestern Regional Renal Transplant Unit at Manchester Royal Infirmary. Through a continuing policy of avoiding mismatches for HLA antigens and lymphocytotoxic antibody crossmatching, transplant survival rates were found to correlate with the degree of HLA-A and B antigen mismatching from 1968 to 1978 and with HLA-B and DR antigen mismatching from 1979 to 1988. Mismatching for HLA-B and DR antigens was also found to correlate with transplant survival in highly sensitized patients and in patients transplanted since 1981, the "cyclosporine era." Recipients who were HLA-DR1 positive were found to have the highest graft survival compared to recipients negative for this antigen. In contrast, HLA-DR3 positive recipients had the poorest outcome. Transplants from HLA-DRw6 positive donors showed higher transplant survival rates than donor kidneys positive for any other HLA-DR antigen. A correlation of transplant survival with HLA-B and DR mismatching was seen whether kidneys were collected within our region or received through the UK Transplant Service. We conclude that avoidance of mismatching for HLA-B and DR antigens confers high transplant survival rates (91.1% at 5 years for 0 HLA-B and DR mismatches), and in order to achieve this rate for most recipients exchange of donor kidneys between transplant centers will be essential.     

Should Pediatric Patients Wait for HLA‐DR‐Matched Renal Transplants?

Graft survival rates from deceased donors aged 35 years or less among all primary pediatric kidney transplant recipients in the United States between 1996 and 2004 were retrospectively examined to determine the effect of HLA‐DR mismatches on graft survival. Zero HLA‐DR‐mismatched kidneys had statistically comparable 5‐year graft survival (71%), to 1‐DR‐mismatched kidneys (69%) and 2‐DR‐mismatched kidneys (71%). When compared to donors less than 35 years of age, the relative rate of allograft failure was 1.32 (p = 0.0326) for donor age greater than or equal to age 35. There was no statistical increase in the odds of developing a panel‐reactive antibody (PRA) greater than 30% at the time of second waitlisting, based upon the degree of HLA‐A, ‐B or ‐DR mismatch of the first transplant, nor was there a ‘dose effect’ when more HLA antigens were mismatched between the donor and recipient. Therefore, pediatric transplant programs should utilize the recently implemented Organ Procurement and Transplantation Network's (OPTN) allocation policy, which prioritizes pediatric recipients to receive kidneys from deceased donors less than 35 years of age, and should not turn down such kidney offers to wait for a better HLA‐DR‐matched kidney.     

Improved definition of human leukocyte antigen frequencies among minorities and applicability to estimates of transplant compatibility

BACKGROUND: HLA population data can be applied to estimates of waiting time and probabilities of donor compatibility. Registry data were used for derivation of HLA antigen and haplotype frequencies in a 1996 report. At that time there were several instances of significant deviation from Hardy Weinberg Equilibrium (HWE). Because molecular typing has been increasingly used since 1996, analysis of recent donor phenotypes should provide more accurate HLA frequencies. METHODS: HLA frequencies were derived from the phenotypes of 12,061 donors entered into the Organ Procurement and Transplantation Network registry from January 1, 2003 to December 31, 2004. Frequencies for HLA-A;B;DR and HLA-A;B, DR, DQ haplotypes were derived from 11,509 and 10,590 donors, respectively. Frequencies of the allele groups encoding serologic antigens were obtained by gene counting and haplotype frequencies were estimated using the expectation maximization algorithm. Fit to HWE was evaluated by an exact test using Markov Chain Monte Carlo methods. RESULTS: There was clear evidence of improved definition of rarer HLA antigens and haplotypes, particularly among minorities. The reported frequencies of broad antigens decreased overall for HLA-A, B, and DR, with concomitant increases in split antigens. Allele group genotypes among the major ethnic groups were in HWE with the single exception of HLA-A locus alleles among Asians. Improved HLA definition also permitted the first report of DR;DQ and A;B;DR;DQ haplotypes among U.S. donors. CONCLUSIONS: The noted improvements in HLA definition and the overall lack of significant deviation from HWE indicate the accuracy of these HLA frequencies. These frequencies can therefore be applied for representative estimates of the U.S. donor population.     

Critical evaluation of the amino acid triplet-epitope matching concept in cadaver kidney transplantation

BACKGROUND: A computer-based approach for determining human leukocyte antigen (HLA) compatibility between kidney donors and recipients on the basis of differences of amino acid sequences as motifs for immunogenic epitopes was proposed by Duquesnoy et al. The HLAMatchmaker algorithm focuses on HLA class I polymorphisms of serologically defined antigens encoded by the HLA-A and -B loci. HLA phenotypic mismatches that represent only a few mismatches at the amino acid triplet level are held to be not or only mildly immunogenic. This approach was proposed as being especially suitable for the allocation of donor kidneys to highly sensitized patients. METHODS: We reexamined this attractive concept using the data of the Collaborative Transplant Study. Intra- and interlocus comparisons for HLA-A and -B were performed according to the original HLAMatchmaker algorithm. To exclude the influence of HLA-DR, only transplants with no HLA-DR mismatch were considered. Patients who had one HLA-A and one HLA-B antigen mismatch were separated into subgroups, depending on the number of triplet mismatches as calculated by the HLAMatchmaker software. Separate analyses were performed for first transplants, retransplants, and patients with a panel-reactive antibody activity of 50% or more. A total of 16,997 white patients matched for HLA-DR who received a cadaver kidney transplant between 1991 and 2001 formed the basis of this analysis. RESULTS: Application of the HLAMatchmaker method could not be shown to result in any statistically significant effect on graft survival. CONCLUSIONS: The HLAMatchmaker concept is theoretically attractive; however, it could not be shown to yield useful results in this analysis. Serologic HLA typing appears to provide an insufficient basis for applying epitope matching in clinical kidney transplantation.     

A new allocation plan for renal transplantation

BACKGROUND: A novel plan of renal allograft allocation has been conducted by United Network for Organ Sharing Region 1 transplant centers since September 3, 1996, based upon HLA matching, time waiting, and population distance points. The objectives of this plan were to achieve a balance between increasing the opportunity of renal transplantation for those patients listed with long waiting times and promoting local organ donor availability. METHODS: A single list of candidates was formulated for each cadaver donor, assigning a maximum of 8 points for time waiting, a maximum of 8 points for population distance from the donor hospital, and HLA points based upon the degree of B/DR mismatch. Additional points were awarded to a cross-match-negative patient with a panel-reactive antibody of >80%, and to pediatric patients. RESULTS: The total number of kidneys transplanted to patients who had waited >3 years was 100 (46%), and to patients who had waited >2.5-3 years was 29 (13%). However, the total number of kidneys transplanted to patients with the maximum population distance points was only 72 (33%). Thus, although the plan achieved a favorable distribution of kidneys to patients with longer waiting times (nearly 60%), the other, equally important objective of promoting local donor availability was not initially accomplished. Moreover, minor HLA B/DR differences between the donor and the recipient (i.e., not phenotypically matched) were unexpectedly consequential in determining allocation. As a result of these observations, the following adjustments were made in the plan (as of December 3, 1997): a maximum of 10 points for population distance, a maximum of 8 points for time waiting (both by a linear correlation), and the retention of HLA points for 0 B/DR mismatch only. After these interval changes, the percentage of patients receiving a kidney with some population distance points increased from 85% to 96%. Conclusions. We have shown that a heterogeneous region of multiple transplant centers can devise (and modify) an innovative and balanced plan that provides an equitable system of allocation for an ever-increasing number of patients.     

Racial disparities in access to pediatric kidney transplantation since share 35

Share 35 was enacted in 2005 to shorten transplant wait times and provide high-quality donors to children with ESRD. To investigate the possible effect of this policy on racial disparities in access to pediatric transplantation, we analyzed data from the US Renal Data System before and after Share 35. Among 4766 pediatric patients with incident ESRD, the probability of receiving a deceased-donor kidney transplant increased 46% after Share 35, with Hispanics experiencing the greatest improvements (increases of 81% for Hispanics, 45% for blacks, and 37% for whites). On average, patients received a deceased-donor kidney transplant earlier after Share 35, but this finding varied by race: 63 days earlier for whites, 90 days earlier for blacks, and 201 days earlier for Hispanics. Furthermore, a shift from living- to deceased-donor sources occurred with Share 35 for all races, with a 25% reduction in living donors for whites compared with 48% and 46% reductions for Hispanics and blacks, respectively. In summary, Share 35 seems to have attenuated racial disparities in the time to and probability of children receiving a deceased-donor kidney transplant. These changes coincided with changes in the rates of living-donor sources, which vary by race. Future studies should explore how these changes may impact racial differences in long-term graft outcomes.     

Human leukocyte antigens DR and AB and kidney retransplantation

BACKGROUND: Although class II human leukocyte antigen (HLA) DR mismatching has been shown to demonstrate a significant effect on kidney regraft survival, it has not generally been clinically emphasized. METHODS: We examined 2,574 kidney retransplants performed in Southeastern Organ Procurement Foundation centers between January 1988 and December 1997 in which there was ABDR typing on both donor and recipient and pretransplant panel reactive antibody (PRA) data. RESULTS: Cox regression of multiple variables demonstrated that the most important risk factors in descending order were DR mismatching, non-white recipient, female donor, PRA as a continuous variable, and cold ischemia time. Although DR mismatching demonstrated a significant effect in white recipients, the impact was much greater in non-white recipients. In both groups, zero to four AB mismatches demonstrated no significant effect on regraft survival if DR was matched and only a minimal effect when DR was mismatched. The discrepancy of these findings with reports that demonstrate a stepwise decrease in regraft survival on the basis of the total zero to six ABDR mismatches was explained by the fact that the zero to six ABDR mismatches are a combination of AB mismatches with little effect and DR mismatches with a major effect. Regraft survival decreased progressively in association with increasing PRA. CONCLUSIONS: DR matching is critically important in kidney retransplantation. There was no significant difference in survival of zero ABDR mismatched retransplants compared with one to four AB and zero DR mismatched retransplants. On the other hand, kidney graft survival of all one to four AB and zero DR mismatches exceeded that of one or two DR mismatched retransplants. We propose that the association of decreasing regraft survival with increasing PRA reflects undetected sensitization to class II, and possibly class I, antigens.     

HLAmatchmaker: a molecularly based algorithm for histocompatibility determination. IV. An alternative strategy to increase the number of compatible donors for highly sensitized patients

BACKGROUND: HLAMatchmaker is a computer algorithm that determines human leukocyte antigen (HLA) compatibility at the level of polymorphic amino acid triplets in antibody-accessible sequence positions. Recent studies have shown that HLA-DR-matched kidney transplant recipients with zero to two triplet mismatches had almost identical graft survival rates as those with zero HLA-A,B,DR antigen mismatches. This report describes how HLAMatchmaker can be used to identify more compatible donors for highly sensitized patients. METHODS: The HLAMatchmaker program was used to calculate the probability of finding a donor (PFD) with zero, one, or two triplet mismatches for 54 highly sensitized patients waiting for a kidney transplant and having panel reactive antibody (PRA) values greater than 85% and 50 randomly selected nonsensitized patients with PRA values less than 3%. RESULTS: There was a wide variability for PFD values for the two patient cohorts. If only donors with zero HLA-A,B mismatches were deemed acceptable for recipients, the median PFD of a zero-antigen mismatch was 0.046% for nonsensitized patients and 0.009% for highly sensitized patients (P=0.007). Half of the highly sensitized patients had a PFD below 0.01%, or fewer than 1 in 10,000 donors would have zero antigen mismatches. Application of HLAMatchmaker identified additional HLA antigens with zero-triplet mismatches for 27 patients, resulting in a 1.8-fold increase in PFD. Considering additional antigens with one-triplet or two-triplet mismatches increased the PFD by an additional 3.8-fold and 13.7-fold, respectively. Acceptable antigen mismatches for 37 of the 54 highly sensitized patients were identified by consistently negative reactions in serum screens, and their addition resulted in a 12.7-fold increase of the PFD to a median of 0.141%. Applying these acceptable antigens to the HLAMatchmaker algorithm identified additional antigens with zero or acceptable triplet mismatches and their inclusion increased the PFD by 3.3-fold to 0.347%. CONCLUSIONS: HLAMatchmaker offers a valuable strategy for identifying more suitably HLA-matched donors and has the potential for alleviating the problem of accumulation of highly sensitized patients on the transplant waiting list.     

An evaluation of HLA cross-reactive group matching on graft survival in deceased donor kidney recipients

Since September 20, 1999, our organ procurement organization (OPO) serving an ethnically diverse local distribution area has allocated kidneys using a cross-reactive group (CREG)-based variance. This variance awards 7 points for 0-CREG,0-DR mismatches and 6 points for 0-A,B mismatches in addition to points given for waiting time (3) and panel-reactive antibodies (PRA) > or = 80% (3). Previously, we have shown that awarding points for 0-CREG,0-DR mismatches in kidney allocation improves the access to HLA-matched transplants for racial groups, especially for the black race. In this study, we evaluated if there are outcome benefits as well. One- and 3-year uncensored graft survival data and analyses for the influence of HLA mismatching on graft outcome in black and nonblack recipients were provided by Scientific Registry of Transplant Recipients (SRTR). Overall, 1-year graft survival was 87.4% and not significantly different for blacks (86.1%, n = 467) vs nonblacks (88.8%, n = 730); 3-year graft survival was 74.6% and significantly lower P = .0001 for blacks (68.5%, n = 480) vs nonblacks (78.4%, n = 765). No significant advantage was observed for either the black or nonblack recipients in any of the HLA-mismatched categories, including the 0-CREG,0-DR mismatch group. An HLA matching effect also was not seen when data were stratified for patients nonsensitized (PRA < or = 10%) and sensitized (PRA > 10%) at the time of transplantation, except for the improved graft survival in sensitized nonblack recipients of 0- A,B,DR-mismatched grafts. Of the patients who lost their grafts and returned to the waiting list for retransplantation, the 0-A,B,DR mismatched were the least sensitized group (6%, n = 16), and there was a trend for less sensitization in the 0-CREG,0-DR-mismatched group (33%, n = 9), compared to those with other HLA mismatches (68%, n = 137). Thus, based on 1-year and 3-year follow-up data, there are no apparent graft outcome benefits for either CREG matching or conventional HLA matching in our service area, except for sensitized nonblack recipients receiving 0-A,B,DR-mismatched grafts. Such benefits may become more apparent with longer follow-up.     

HLAmatchmaker: a molecularly based algorithm for histocompatibility determination. III. Effect of matching at the HLA-A,B amino acid triplet level on kidney transplant survival

BACKGROUND: HLAMatchmaker is a recently developed computer-based algorithm to determine donor-recipient HLA compatibility at the molecular level. Originally designed for highly alloimmunized patients, this algorithm is based on the concept that immunogenic epitopes are represented by amino acid triplets on exposed parts of protein sequences of HLA-A, -B, and -C chains accessible to alloantibodies. Donor HLA compatibility is determined by intralocus and interlocus comparisons of triplets in polymorphic sequence positions. For most patients, HLAMatchmaker can identify certain mismatched HLA antigens that are zero-triplet mismatches to the patient's HLA phenotype and should, therefore, be considered fully histocompatible. The present study was designed to determine how class I HLA matching at the triplet level affects kidney transplant outcome. METHODS: We analyzed two multicenter databases of zero-HLA-DR-mismatched kidneys transplanted from 1987 to 1999. One database consisted of 31,879 primary allografts registered by U.S. transplant centers in the United Network for Organ Sharing database and the other consisted of 15,872 transplants in the Eurotransplant program. RESULTS: HLA-A,B mismatched kidneys that were compatible at the triplet level exhibited almost identical graft survival rates as the zero-HLA-A,B antigen mismatches defined by conventional criteria. This beneficial effect of triplet matching was seen for both nonsensitized and sensitized patients and also for white and nonwhite patients. CONCLUSIONS: These findings suggest that the application of HLAMatchmaker will increase the number of successful transplants, at least in the HLA-DR match combinations.     

HLA mismatch is important for 20-year graft survival in kidney transplant patients

BackgroundHuman leukocyte antigens (HLA) matching is gradually being omitted from clinical practice in evaluation for renal allograft transplant. While such practices may yield shorter wait times and adequate short-term outcomes, graft longevity in HLA mismatched patients remains unclear. This study aims to demonstrate that HLA matching may still play an important role in long-term graft survival.MethodsWe identified patients undergoing an index kidney transplant in the United Network for Organ Sharing (UNOS) data from 1990 to 1999, with one-year graft survival. The primary outcome of the analysis was graft survival beyond 10 years. We explored the long-lasting impact of HLA mismatches by landmarking the analysis at established time points.ResultsWe identified 76,530 patients receiving renal transplants in the time frame, 23,914 from living donors and 52,616 from deceased donors. On multivariate analysis, more HLA mismatches were associated with worse graft survival beyond 10 years for both living and deceased donor allografts. HLA mismatch continued to remain an essential factor in the long term.ConclusionsA greater number of HLA mismatches was associated with progressively worse long-term graft survival for patients. Our analysis reinforces the importance of HLA matching in the preoperative evaluation of renal allografts.     

Prolonged cold ischemia time obviates the benefits of 0 HLA mismatches in renal transplantation

HYPOTHESIS: Recipients of 0 HLA mismatch kidneys with prolonged cold ischemia times of longer than 36 hours do not have superior outcomes compared with recipients of kidneys with 1 or more mismatches. DESIGN: Retrospective review. SETTING: Transplanation centers. PATIENTS AND METHODS: A total of 63,688 recipients who underwent transplantation between January 1, 1990, and July 31, 1998. MAIN OUTCOME MEASURES: Delayed graft function, serum creatinine level, and patient and renal graft survival. RESULTS: Recipients of 0 HLA mismatch kidneys with fewer than 36 hours of cold ischemia time had better 5-year graft survival (75%) when compared with recipients with 1 or more mismatches (67%) (P<.001). However, recipients of 0 HLA mismatch kidneys with longer than 36 hours of cold ischemia time did not have any graft survival advantage (71% in 0 HLA mismatch kidneys vs 72% in 1 or more mismatches, P =.24). CONCLUSIONS: Cold ischemia times of longer than 36 hours obviate the benefits of better graft survival conferred by better matching.     

Unintended Consequences of the New National Kidney Allocation Policy in the United States

The new national Kidney Allocation System of the Organ Procurement and Transplantation Network (OPTN), effective as of December 4, 2014, was designed to improve the chances of transplanting the most highly sensitized patients on the waitlist, those with calculated panel reactive antibody values of 98%, 99% and 100%. Recently, it was suggested that these highly sensitized patients will experience inequitable access, given the reported high prevalence of antibodies to HLA‐DP, and the fact that only about 1/3 of deceased donors are typed for HLA‐DP antigens. Here we report that 320/2948 flow cytometric crossmatches performed for the Northwestern transplant program over the past 28 months were positive solely due to HLA‐DP donor‐specific antibodies (11%; 16.5% of patients with HLA antibodies—sensitized patients). We further show that 58/207 (12%) HLA‐DR serologically matched donor‐recipient pairs had a positive B cell flow crossmatch due to donor‐specific HLA class II antibodies, and 2/34 (6%) serologic zero‐HLA‐A‐B‐DR mismatch had a positive flow crossmatch due to HLA‐DSA. We therefore provide information regarding the necessity and importance of complete donor HLA typing including both chains of the HLA‐DP antigen (encoded by HLA‐DPA1 and HLA‐DPB1) at the time of organ offer.     

Success rate and impact of HLA matching on kidney graft survival in highly immunized recipients

From 1985 to 1990, 225 highly immunized recipients were transplanted based on a program of serum exchange and priority allocation of kidneys to crossmatch negative recipients. The 1-year graft survival rate in first transplant recipients was 73% and in second transplant recipients, 71 %. Recipients of third or fourth transplants had a 25 % lower success rate. HLA matching exerted a significant influence on graft outcome. Twenty-five first or second grafts with zero mismatches for HLA-B,-DR had a 91 % 1-year survival rate, in contrast to a 58% survival rate of 38 grafts with of three or four HLA-B,-DR mismatches (log rank P < 0.001).     

Assessment of optimal size and composition of the U.S. National Registry of hematopoietic stem cell donors

BACKGROUND: The National Marrow Donor Program (NMDP) receives federal funding to operate a registry of over 4 million volunteer donors for patients in need of a hematopoietic stem cell transplant. Because minority patients are less likely to find a suitably matched donor than whites, special efforts have been aimed toward recruitment of minorities. Significant financial resources are required to recruit and tissue type additional volunteer donors. METHODS: Population genetics models have been constructed to project likelihoods of finding a human leukocyte antigen (HLA)-matched donor for patients of various racial/ethnic groups. These projections have been made under a variety of strategies for expansion of the NMDP Registry. Cost-effectiveness calculations incorporated donor unavailability and other barriers to transplantation. RESULTS: At current recruitment rates, the probability of an available HLA-A,B,DRB1 matched donor is projected to increase from 27% to 34%; 45% to 54%; 75% to 79%; and 48% to 55%, for blacks, Asians/Pacific Islanders, whites and Hispanics, respectively, by the year 2007. Substantial increases in minority recruitment would have only modest impacts on these projections. These projections are heavily affected by donor availability rates, which are less than 50% for minority volunteers. CONCLUSIONS: Continued recruitment of additional volunteers can improve the likelihood of finding an HLA-matched donor, but will still leave significant numbers of patients of all racial/ethnic groups without a match. Efforts to improve donor availability (especially among minorities) and to increase the number of patients with access to the NMDP Registry may prove to be more cost-effective means of increasing transplants.     

The effect of HLA-C matching on acute renal transplant rejection.

BACKGROUND: The acute immunological rejection and long time survival of kidney allografts are correlated with the human leukocyte antigen (HLA) match status between donor and recipient. HLA-A, -B and -DR have all turned out to be relevant HLA loci in several studies. The role of HLA-C has not been studied before now. METHODS: In 104 consecutive patient/donor pairs from our transplantation unit, we retrospectively analysed whether acute graft rejection is influenced by HLA-C match status between donor and recipient. For typing HLA-C alleles, we used an allele-specific PCR protocol in combination with serology. RESULTS: By analysing groups of donor/recipient pairs with a homogeneous distribution of HLA-B mismatches in order to exclude an effect of the linkage disequilibrium between HLA-B/C, HLA-C mismatch turned out to be significantly correlated with acute transplant rejection in pairs with one additional mismatch on the B locus (P=0.004). Additional parameters that may hypothetically influence acute rejection episodes (HLA-A or DR mismatch, time of cold and warm ischaemia, previous transplantations, pre-existing HLA antibodies) were also analysed but cannot explain this finding. CONCLUSION: HLA-C matching of all kidney donors and recipients seems to be an option to reduce the probability of acute rejection episodes. Further studies of greater patient cohorts analysing organ rejection and organ survival are warranted.     

The impact of the UNOS mandatory sharing policy on recipients of the black and white races--experience at a single renal transplant center.

The impact of the United Network for Organ Sharing mandatory sharing policy on a large transplant center procuring kidneys primarily from caucasians while serving a pool of prospective recipients composed mainly of blacks is described. This policy requires that all 6-antigen-matched and phenotypically identical donor kidneys be shipped to the appropriately matched recipients. The study consisted of 49 kidneys from 25 cadaveric donors; one kidney was unusable. In general, the 33 recipients of the mandatorily shared kidneys were caucasian (94%), unsensitized (70%), and first-time transplants (73%). Allograft survival for the 24 first-time recipients was 100% (mean graft survival = 11.3 months). Of the 9 regraft kidneys, 2 have failed (mean graft survival = 11.9 months) due to chronic rejection. In comparison, the 16 paired kidneys transplanted into non-6-antigen-matched recipients exhibited a 1-year graft survival of 80% versus 92% for the 33 recipients of mandatorily shared kidneys (P = 0.01). These 16 recipients were composed of more blacks (38%), fewer regrafts (6%), and most were unsensitized (75%). All 25 cadaveric donors were caucasians with very common HLA types. Thus, kidneys provided by the UNOS mandatory sharing policy had excellent allograft survival, and the recipients were largely unsensitized caucasians receiving their first kidney. The low number of blacks receiving allografts under this policy may be due to two factors. First, the histocompatibility differences between black recipients and the primarily caucasian cadaveric donor pool limit the number of kidneys available to blacks. Secondly, blacks do not have access to the best-matched kidneys, in part due to few black donors, their best source for well-matched kidneys. Thus, the mandatory sharing program is of clear benefit to the recipients of these well-matched kidneys; however, for a local program servicing a waiting list composed of 64% blacks the policy has been of limited value. In contrast, over 50% of local cadaveric transplants are into black recipients in a waiting time of 197 days, one third the national average for blacks. In conclusion, this study supports efforts to improve graft survival through matching but emphasizes the need to broaden our efforts in all areas of research and organ procurement to serve the entire recipient population, regardless of race.