Allocation of cadaver donor kidneys in Australia

The national allocation of kidneys in Australia is based on a combination of human leukocyte antigen (HLA) matching and equity factors designed to make transplantation accessible to as many patients as possible. A points system has been designed that deducts points for HLA mismatches but adds points for factors such as levels of HLA sensitization, waiting time on dialysis, and a loading for pediatric patients. Kidneys that do not reach the level of matching required for national allocation are transplanted in the donor state using both matching and waiting time criteria, which caters to minority groups with rare HLA types.     

Human leukocyte antigen in the allocation of kidneys from cadaveric donors in the United States

Minorities wait longer for a cadaveric donor kidney transplant than whites. For example, the median waiting time to transplant for candidates listed from 1997 to 1998 was 874 days for whites, 1,493 days for blacks, 1,281 days for Hispanics, 1,491 days for Asians, and 1,466 days for others. The current allocation algorithm has been criticized as contributing to decreased access to transplants for racial minorities. There are two levels in the current algorithm: The first is mandatory national sharing between donors and patients with zero human leukocyte antigen (HLA)-A, B, and DR mismatches. The second occurs if there are no candidates and local placement is accomplished based on an algorithm with an HLA component that assigns seven, five, and two points to zero, one, and two HLA-B and DR mismatches, respectively. An analysis of the data shows that a higher percentage of white recipients (21%) received zero antigen mismatched kidneys compared with other races: blacks (7%), Hispanics (14%), and Asians (7%). Whites also received the highest percentage of kidneys with zero B and DR mismatches and one B and DR mismatch compared with the other races. These data indicate that the current algorithm favors whites over minorities, and it is most likely that giving points for HLA-B matching is a strong contributory factor. To address this inequity, the Organ Procurement and Transplantation Network and United Network for Organ Sharing Board of Directors approved a recommendation in November 2002 to change the HLA points to award two points for zero DR mismatches and one point for one DR mismatch. Obviously it will take some time to gather sufficient data to allow meaningful analysis of the effect of the policy change.     

It takes six to boogie: allocating cadaver kidneys in Eurotransplant

In March 1996, a new allocation point system for cadaver kidneys, the Eurotransplant (ET) Kidney Allocation System (KAS), was introduced in ET, the first multinational organ exchange organization. The aims of ETKAS were to reduce average and maximum waiting time, to allow patients with rare human leukocyte antigen (HLA) phenotypes or combinations to receive an "optimal" offer, to keep the exchange rates between the participating countries balanced, and finally to keep optimal graft survival, by means of HLA matching. Elderly patients and highly sensitized patients profit in addition from special programs, the ET Senior Program and the Acceptable Mismatch Program, respectively. All kidneys are offered to the pool and are allocated according to the degree of HLA matching, mismatch probability, waiting time, distance from the donor center, and balance between the countries participating in ET. A summary of 6 years' experience with the ETKAS is presented in this article.     

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.     

A novel united network for organ sharing region kidney allocation plan improves transplant access for minority candidates

BACKGROUND: We report the consequences of a novel kidney allocation system on access of non-Caucasians (NC) to kidney transplantation. This new plan has provided a balance of allocation determinants between time waiting, HLA match, and geography (population density between donor and recipient center). METHODS: Three sequential systems of regional allocation were analyzed: period I (September 1994 to September 1996), period II (September 1996 to November 1997), and period III (December 1997 to March 1 1999). Periods II and III are reflective of the new allocation plan. RESULTS: During periods II and III, the NC rate of kidney transplantation increased closer to the NC proportion on the wait list, comparatively exceeding the national UNOS data. There was no statistical difference in regional mean wait time between Caucasian and NC. Improvements in access to transplantation for NCs between period I and periods II and III appear to be related to changes in geographic allocation weight from local unit to population density points, to the inclusion of the entire region in the plan, and to the deletion of intermediate degrees of B/DR mismatching in the revised plan. Despite the increased proportion of NCs on the wait list from period I to period III, the percentage difference between the proportion of NCs waiting on the list and the proportion NCs receiving a transplant fell from 7.8% to 4.9%. CONCLUSIONS: These data demonstrate that this new allocation plan was associated with improved access of minority candidates to transplantation. The broadening of geographic allocation and the alteration of HLA points appear to permit a more favorable opportunity for renal transplantation to NC candidates. selection, compared to the UNOS formula. In this report, we analyze the consequences of the Region 1 allocation system on the access of non-Caucasian (NC) candidates to cadaver donor kidney transplantation.     

Comparison of blood group versus HLA-dependent transplantation and its influence on donor kidney survival.

BACKGROUND: The advantages of organ allocation based on human leukocyte antigen (HLA) typing are controversial. This evaluation compares the results of HLA-dependent and non-HLA-dependent allocation in the transplantation of donor kidneys. METHODS: Seventy-seven donor kidney pairs explanted locally between 1984 and 1994 were examined. One half of each pair was transplanted locally in Bonn on the basis of criteria including blood group, waiting time and currently negative cross-match. The other half of these pairs was allocated in accordance with the Eurotransplant (ET) criteria. RESULTS: Cold ischaemia time was an average of 14.02 h in Bonn vs. 24.18 h in the ET group (P<0.0001). The number of HLA mismatches was calculated and, for example, for locus A it was 1.13 in Bonn vs. 0.73 in the ET group (P=0.0003). One-year graft survival for the locally transplanted kidneys was 92.2% and, for the ET kidneys, 90.9%. Five-year survival was 79.5% vs. 81.7%, respectively. Patient survival after 1 year was 100% vs. 97.4%, and after 5 years, 93.4% vs. 93.1%. CONCLUSION: The results show that it is possible to provide patients with a locally allocated kidney graft that enables good function after a short waiting period. This procedure avoids long cold ischaemia time and long waiting periods.     

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.     

An algorithm for cadaver kidney allocation based on a multivariate analysis of factors impacting on cadaver kidney graft survival and function

Abstract The large imbalance between cadaver kidney supply and demand makes the implementation of equitable and effective organ allocation systems an urgent need. This has triggered a revision of the criteria used so far for cadaver kidney allocation within the North Italy Transplant program, not least in the light of the many changes that have occurred recently with respect to broader criteria for admission of patients to the waiting list, donor selection, tissue‐typing methods, organ preservation and immunosuppressive protocols. We based the critical revision of our cadaver kidney allocation algorithm on univariate and multivariate analysis of a number of immunological, clinical, social and administrative factors that impacted on the transplant outcome in 2,917 patients transplanted in the 12 transplant centers operating within our organization from 1 January 1990 to 30 September 1997. This analysis indicated that younger donor age, absence of pretransplant transfusions, patient dialysis center and level of HLA match showed statistically significant positive associations with graft survival. Younger donor age and male donor gender showed a statistically significant association with excellent graft function at 4 years. The results of this analysis were used to develop a new computer‐assisted version of our adult kidney allocation algorithm. It works in two steps (local pool first, then the entire waiting list) and four levels (0‐1 HLA MM, PRA +; 2 HLA MM, PRA +; 0‐1 MM, PRA‐; 2‐4 HLA MM, PRA‐); within each level, selection takes into account waiting time and age difference from donor age. The evaluation of 731 transplants allocated in 19 months with the new algorithm, as against 698 transplants allocated in the preceding 19 months according to the previous algorithm, showed a significantly higher proportion of recipients who had been on the waiting list for more than 3 years (33.2% versus 22.6%). The use of the new algorithm was also associated with a significantly increased number of transplanted alloimmunized patients (18.8% versus 9.2% with the previous algorithm) and recipients with 0‐1 HLA mismatches (22% versus 14.3%). Furthermore, the number of kidneys used locally has steadily increased. Differences in 6‐month graft survival and percentage of patients with excellent function at 6 months were not statistically significant in recipients transplanted with the new versus the previous algorithm. Survivals were 93.7% versus 91.8%. Percentages of patients with excellent renal function were 69.9% and 71.8%, respectively. These preliminary data suggest that the new algorithm improves HLA match and reduces the number of patients on the waiting list for 3 or more years without determining significant modifications of 6‐month graft survival and function. Moreover, it facilitates the achievement of a fair local balance between organs retrieved and transplanted, the compliance of operators with objective allocation rules and the documentation of the whole allocation process.     

Allocation of Deceased Donor Kidneys in São Paulo, Brazil: Effect of Human Leukocyte Antigen Compatibility on Graft Survival

In Brazil, organ transplantation has been regulated by a federal law since 1997. This law was created to guarantee equal access to treatment on a national scale. Deceased donor organ procurement and sharing are centralized and controlled by the Health Department of each state of the nation, following a regional allocation policy. In São Paulo, time on the waiting list was the main criterion adopted to allocate deceased donor kidneys up to January 1, 2002. After that, HLA mismatches (MM) were the main criterion. The aim of this study was to investigate the impact of HLA compatibility on graft survival among 3312 consecutive kidney recipients. The 2-year kidney graft survival rates were compared among recipients transplanted based on the waiting time policy and based on HLA MM. Better results were observed in the HLA MM group (78.1% vs 64.9%; P < .0001). Regarding kidney allocation based on HLA MM, recipients transplanted with 0 HLA-A, -B, or -DR MM showed significantly better 5-year survival rates than those with 1-2 or 3-4 or 5-6 HLA-A, -B, or -DR MM (70.36% vs 64.71% vs 58.07% vs 55.64%; P < .050). We concluded that HLA compatibility is a feasible criterion to allocate deceased donor kidneys in Brazil.     

A Europe wide acceptable mismatch program will enable transplantation of long waiting highly sensitised patients with a compatible donor

Immunisation against Human Leucocyte Antigens (HLA) can be caused by pregnancy, blood transfusion, or organ transplants. The HLA antibody status of a given patient significantly influences their access and waiting time to transplant. For some highly sensitised patients (HSP) there is hardly any suitable donor available in the deceased donor pool of their allocation organisation and therefore they wait a very long time before being offered a kidney for transplant. Especially patients with rare HLA phenotypes in relation to the actual donor pool are waiting extremely long. As HLA phenotypes are different in the various European populations, we hypothesized that extension of the donor pool outside the respective allocation system will increase the chance of receiving a compatible transplant for this subgroup of highly sensitised patients. One of the objectives of the EUROSTAM project, (a Europe-wide Strategy to enhance Transplantation of highly sensitised patients on the basis of Acceptable HLA Mismatches) was to develop a tool to compare the chance of transplanting HSP in different European populations with donor organs from within and outside their own donor pool.Information on the HLA type and ABO blood group of the actual donor population, as well as the acceptable mismatches of long waiting HSP were obtained from the EUROSTAM partner organizations i.e. Eurotransplant (ET), UK National Health Service Blood and Transplant (NHSBT), Barcelona, Prague and Athens.Results from simulations using the newly developed tool shows that 195 (27%) of the 724 long waiting highly sensitised patients registered at each partner organisation have increased chances of transplant in a different European donor pool. This makes a strong case for sharing kidneys between European countries for selected difficult to transplant patients.     

The PROCARE consortium: Toward an improved allocation strategy for kidney allografts

Kidney transplantation is the best treatment option for patients with end-stage renal failure. At present, approximately 800 Dutch patients are registered on the active waiting list of Eurotransplant. The waiting time in the Netherlands for a kidney from a deceased donor is on average between 3 and 4 years. During this period, patients are fully dependent on dialysis, which replaces only partly the renal function, whereas the quality of life is limited. Mortality among patients on the waiting list is high. In order to increase the number of kidney donors, several initiatives have been undertaken by the Dutch Kidney Foundation including national calls for donor registration and providing information on organ donation and kidney transplantation. The aim of the national PROCARE consortium is to develop improved matching algorithms that will lead to a prolonged survival of transplanted donor kidneys and a reduced HLA immunization. The latter will positively affect the waiting time for a retransplantation.The present algorithm for allocation is among others based on matching for HLA antigens, which were originally defined by antibodies using serological typing techniques. However, several studies suggest that this algorithm needs adaptation and that other immune parameters which are currently not included may assist in improving graft survival rates. We will employ a multicenter-based evaluation on 5429 patients transplanted between 1995 and 2005 in the Netherlands. The association between key clinical endpoints and selected laboratory defined parameters will be examined, including Luminex-defined HLA antibody specificities, T and B cell epitopes recognized on the mismatched HLA antigens, non-HLA antibodies, and also polymorphisms in complement and Fc receptors functionally associated with effector functions of anti-graft antibodies. From these data, key parameters determining the success of kidney transplantation will be identified which will lead to the identification of additional parameters to be included in future matching algorithms aiming to extend survival of transplanted kidneys and to diminish HLA immunization. Computer simulation studies will reveal the number of patients having a direct benefit from improved matching, the effect on shortening of the waiting list, and the decrease in waiting time.     

Prospective Age-Matching in Elderly Kidney Transplant Recipients—A 5-Year Analysis of the Eurotransplant Senior Program

Renal transplantation faces challenges: the organ shortage resulting in extended waiting times and an aging population resulting in death with a functioning graft. The Eurotransplant Senior Program (ESP) allocates kidneys within a narrow geographic area from donors aged ≥65 years to recipients ≥65 years regardless of HLA. This analysis investigates the impact of the ESP on waiting time, graft and patient survival. The ESP group (n = 1406, old to old) was compared to two groups allocated via the Eurotransplant Kidney Allocation System (ETKAS) with either similar donor age (old to any [O/A], donor age ≥65, n = 446) or recipient age (any to old, [A/O], recipient age 60–64, n = 1687). All patients were transplanted between 1999 and 2004. Since initiation of the ESP (1999), availability of elderly donors doubled and waiting time for ESP patients decreased. Local allocation led to shorter cold ischemia time (11.9 vs. >17.0 h, p < 0.001) and less delayed graft function (DGF, ESP 29.7% vs. O/A 36.2%, p = 0.047) but 5–10% higher rejection rates. Graft and patient survival were not negatively affected by the ESP allocation when compared to the standard allocation. The ESP age matching of elderly donors and recipients is an effective allocation system for organs from elderly donors.     

Evolution in allocation rules for renal, hepatic, pancreatic and intestinal grafts

Organ transplantation is the victim of his own success. The results of transplantation are excellent and more patients are activated on the waiting list. The need for organs exceeds the supply. Which criteria are used to allocate available grafts to patients on the waiting list ? Organ allocation and finding the "best match" between donor and recipients, is the goal of Eurotransplant, the organ sharing organization for seven European countries (Austria, Croatia, Germany, Luxemburg, Slovenia, The Netherlands and Belgium). Last decade, the allocation system has switched from a "center-driven" (organ allocated to a center) to a "patient-driven" system (organ allocated to a particular patient). For the allocation of abdominal organs some general allocation rules are followed: blood group compatibility, priority for high urgencies. The allocation of kidneys is based on a point score system based on waiting time, HLA and donor location (to reduce the cold ischemia time). In addition to this standard allocation procedure, there are still specific procedures for pediatric recipients and for candidates > or = 65 year old. There is also an "acceptable" mismatch program for recipients at high immunological risk. The liver allocation system recently changed and is now based on the MELD score, a formula that calculates the probability of death within 3 months on the waiting list. For pancreas and intestine, the system is based on blood group, medical urgency, waiting time, donor region and weight (for intestine).     

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.     

Alloantibody Responses After Renal Transplant Failure Can Be Better Predicted by Donor–Recipient HLA Amino Acid Sequence and Physicochemical Disparities Than Conventional HLA Matching

We have assessed whether HLA immunogenicity as defined by differences in donor–recipient HLA amino‐acid sequence (amino‐acid mismatch score, AMS; and eplet mismatch score, EpMS) and physicochemical properties (electrostatic mismatch score, EMS) enables prediction of allosensitization to HLA, and also prediction of the risk of an individual donor–recipient HLA mismatch to induce donor‐specific antibody (DSA). HLA antibody screening was undertaken using single‐antigen beads in 131 kidney transplant recipients returning to the transplant waiting list following first graft failure. The effect of AMS, EpMS, and EMS on the development of allosensitization (calculated reaction frequency [cRF]) and DSA was determined. Multivariate analyses, adjusting for time on the waiting list, maintenance on immunosuppression after transplant failure, and graft nephrectomy, showed that AMS (odds ratio [OR]: 1.44 per 10 units, 95% CI: 1.02–2.10, p = 0.04) and EMS (OR: 1.27 per 10 units, 95% CI: 1.02–1.62, p = 0.04) were independently associated with the risk of developing sensitization to HLA (cRF > 15%). AMS, EpMS, and EMS were independently associated with the development of HLA‐DR and HLA‐DQ DSA, but only EMS correlated with the risk of HLA‐A and ‐B DSA development. Differences in donor–recipient HLA amino‐acid sequence and physicochemical properties enable better assessment of the risk of HLA‐specific sensitization than conventional HLA matching.     

Improved Scoring System to Assess Adult Donors For Cadaver Renal Transplantation

We previously proposed a quantitative approach to assess donor organs for cadaver renal transplantation. To improve on our original scoring system, we studied 34 324 patients who received cadaver renal transplants from adult donors between 1994 and 1999 and were reported to the UNOS Scientific Renal Transplant Registry. A scoring system was developed from five donor variables (age, 0-25 points; history of hypertension, 0-4; creatinine clearance before procurement, 0-4; cause of death, 0-3; HLA mismatch, 0-3) that showed a significant correlation with renal function and long-term graft survival. Cadaver kidneys were stratified by cumulative donor score: grade A, 0-9 points; grade B, 10-19; grade C, 20-29; and grade D, 30-39. The influence of donor score on renal function and graft survival was most severe above 20 points, designated 'marginal' kidneys. In summary, a donor scoring system developed from a large population database was useful in predicting outcome after cadaver renal transplantation. The improved system provides a quantitative approach to evaluation of marginal kidneys and may improve allocation of these organs in cadaver renal transplantation.     

Kidney transplant candidate evaluation

The practicing nephrologist is an indispensable component in the evaluation of the candidate for kidney transplantation, from referral to the transplant center to eventual transplantation, which now may be years later. Early referral may lead to preemptive transplantation, the ideal that has been achieved in 25% of living donor transplant cases. Annually approximately 30% of U.S. deceased donor kidneys are now transplanted under the allocation policies for zero human leukocyte antigen (HLA) mismatch kidneys and expanded criteria donor kidneys. Under either of these programs, candidates may receive a kidney offer soon after entering the wait-list, so prompt and complete evaluation and preparation by the practicing nephrologist is necessary for successful early transplantation. The remaining candidates require periodic review while ascending the wait-list and thorough repeat evaluation when nearing the top, as years may have passed since initial evaluation. Wait-list management is a major challenge faced by transplant centers, aggravated by the inexorable growth of the list. Active communication between the practicing nephrologist and the transplant center is essential to maintain the candidate's preparation for transplantation.     

Increased Access to Transplantation for Blood Group B Cadaveric Waiting List Candidates by Using A2 Kidneys: Time for a New National System?

Since blood group B end-stage renal disease (ESRD) patients have less access to donor kidneys and a higher minority composition than any other blood group, the United Network for Organ Sharing (UNOS) approved a voluntary national kidney allocation variance to allow organ procurement organizations (OPOs) to preferentially allocate A2 and A2B kidneys to B candidates. The Midwest Transplant Network OPO has preferentially allocated and transplanted kidneys from blood group A2 and A2B donors to our blood group B waiting list candidates for more than 7 years to increase access to kidneys for the B candidates on our OPO-wide waiting list. Between 1994 and 2000, a total of 121 blood group B ESRD patients from our OPO-wide cadaveric kidney waiting list were transplanted. Thirty-four per cent (41/121) of those B candidates received either an A2 or an A2B kidney. One- and 5-year graft survival rates for the group of B recipients of A2 or A2B kidneys were 91 and 85% (died with functioning graft [DWFG] censored), respectively, which were not significantly different from those of 91 and 80% for the 80 B recipients of B or O kidneys (Wilcoxon = 0.48; log-rank = 0.55). These data support the national trial for additional OPOs to voluntarily allocate A2 and A2B kidneys preferentially to B waiting list candidates, thus increasing access of blood group B patients to renal transplantation.     

Prospective trial of a predictive algorithm to transplant cadaver kidneys into highly sensitized patients

BACKGROUND: The difficulty of transplanting sensitized patients increases proportionally to the panel reactive antibody (PRA) titer. Because of the high likelihood of a positive final crossmatch, these patients are often excluded from a prospective transplant unless there is a 0 HLA-A, -B, -DR mismatch. To address this problem, we developed a computerized algorithm, termed the Kentucky Antibody Testing System (KATS), that predicts class I HLA antigens that would be both "unacceptable" and "acceptable" to the recipient. This report describes the results of a prospective trial among voluntarily participating centers that agreed to share kidneys based on the KATS predictions for patients whose PRA exceeded 40%. METHODS: The results of three antibody screens on each patient were compared with the HLA phenotypes of the cells in the panel in 2x2 tables with calculation of chi-square and correlation coefficient statistics. Private, broad, and public antigens were identified and a list of acceptable and unacceptable antigens were entered into the UNOS computer for each patient listed in the KATS sharing algorithm. RESULTS: Of the total 418 patients meeting the inclusion/exclusion criteria, the largest single group submitted was Black-not-of-Hispanic-origin females. The mean PRA of the patients was 72%. The first transplant via KATS allocation was performed on March 8, 1997. Between that time and the last transplant on July 31, 2000, 145 kidneys were offered to the participating centers and 48 transplants were performed. Of the many reasons listed for not accepting an offer or not transplanting the shared kidney into its intended recipient, only two occurred because of a positive T cell crossmatch and six because of a positive B cell crossmatch. As compared to all other high PRA patients within Southeastern Organ Procurement Foundation who were transplanted during the study period, they were more likely to be non-Caucasian, to be less well matched for private HLA-A, B, and DR antigens, and to have waited for a longer time than the other groups. Although there was a higher incidence of delayed graft function, there was no significant difference in cold ischemia, rejection episodes, or patient or graft survival. CONCLUSIONS: We conclude that KATS, or some other system to prospectively identify a list of acceptable and unacceptable HLA antigens, could improve the access of highly sensitized patients to a successful kidney transplant.     

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.