Model for End-Stage Liver Disease: Impact of the New Deceased Donor Liver Allocation Policy in São Paulo, Brazil

Since 1997, organ transplantation in Brazil has been regulated by a federal law, which was created to guarantee equal access to treatment on a national scale. Centralized deceased donor organ procurement and sharing are 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 livers up to July 15, 2006. After that, model for end-stage liver disease/pediatric end-stage liver disease (MELD/PELD) scores were the main criteria. The aim of this study was to investigate the impact of the new criteria on patient survival rates using 895 consecutive liver recipients. The 1-year patient survival rates were compared between recipients transplanted based on the waiting time policy and based on MELD/PELD scores showing similar results (69.79% vs 66.69%; P = NS). Regarding liver allocation based on MELD/PELD scores, worse survival outcomes were observed among recipients transplanted with higher MELD scores. Also, under the new criteria, a high frequency of hepatocellular carcinoma and pediatric recipients underwent transplantation.     

Cross-reactive group matching does not lead to a better allocation and survival of donor kidneys

BACKGROUND: In cadaveric renal transplantation HLA-A, -B, -DR matching of donor and recipient is beneficial for graft survival. However, allocation based on HLA matching seems to favor recipients with more frequently occurring HLA antigens. In this study we investigated whether matching on the basis of cross-reactive groups (CREGs), defined according to the United Network for Organ Sharing (UNOS), would be a good alternative for the allocation of kidneys without negatively influencing graft survival. Theoretically, this approach would provide more recipients with an immunologically well-matched donor organ. METHODS: The influence of CREG matching on graft survival was studied in univariate analyses using the Eurotransplant database. RESULTS: No beneficial effect of CREG matching was observed, whereas a significant HLA matching effect was observed in the 0 CREG mismatched donor/ recipient combinations. Only in the small subgroup with 1 MM for HLA-A, -B and 0 MM for HLA-DR, a significantly better survival was observed, when this mismatch belonged to the 0 or 1 MM CREG group versus two or more MM CREG group. However, this subgroup concerns only 8% of the transplants performed. CONCLUSIONS: In contrast to other reports, our study showed that HLA matching is by far more beneficial than CREG matching. In the homogenous Eurotransplant population, adjusting the matching criteria toward CREG matching would not lead to an improved graft survival.     

Assessment of differences in HLA-A, -B, and -DRB1 allele mismatches among African-American and non-African-American recipients of deceased kidney transplants

Among recipients of deceased donor kidney transplants, African-Americans experience a more rapid rate of kidney allograft loss than non-African-Americans. The purpose of this study was to characterize and quantify the HLA-A, -B, and -DRB1 allele mismatches and amino acid substitutions at antigen recognition sites among African-American and non-African-American recipients of deceased donor kidney transplants matched at the antigen level. In recipients with zero HLA antigen mismatches, the degree of one or two HLA allele mismatches for both racial groups combined was 47%, 29%, and 11% at HLA-DRB1, HLA-B, and HLA-A, respectively. There was a greater number of allele mismatches in African-Americans than non-African-Americans at HLA-A (P < .0001), -B (P = .096), and -DRB1 loci (P < .0001). For both racial groups, the HLA allele mismatches were predominantly at A2 for HLA-A; B35 and B44 for HLA-B; but multiple specificities for HLA-DRB1. The observed amino acid mismatches were concentrated at a few functional positions in the antigen binding site of HLA-A and -B and -DRB1 molecules. Future studies are ongoing to assess the impact of these HLA mismatches on kidney allograft loss.     

Improving access to kidney transplantation without decreasing graft survival: long-term outcomes of blood group A2/A2B deceased donor kidneys in B recipients

BACKGROUND: The transplantation of blood group A2/A2B deceased donor kidneys into B recipients could improve access to transplantation for blood group B recipients. However, this practice is controversial, and long-term data are lacking. This study analyzed the long-term outcomes of A2/A2B deceased donor kidneys transplanted into selected B recipients. METHODS: We retrospectively assessed the outcomes (graft survival, transplant rates, and acute rejection) of deceased-donor kidneys using an allocation system that transplanted A2/A2B donors into B recipients with low anti-A blood group antibody titers between 1994 and 2003. Patients received conventional immunosuppression without any specific antibody reduction procedures. We further assessed the impact this system had on access to transplantation by blood group. RESULTS: Of 1,400 kidney transplants, 56 (4.0%) were A2/A2B to B recipients. The system reduced waiting time for all B recipients, even shorter than for blood group A recipients (median waiting times of A2/A2B to B transplants=182 days vs. B to B transplants=297 days; and A to A=307 days). Although there was a trend toward increased acute rejection in A2/A2B to B transplants, the actuarial 7-year death censored graft survival was 72% for B recipients regardless of donor type. CONCLUSIONS: Transplanting A2/A2B deceased donor kidneys into B recipients leads to an equalization of waiting time between blood groups with similar patient and graft survival using conventional immunosuppression. This protocol could lead to more equal access to kidney transplantation in blood group B recipients.     

The interaction between the Lewis blood group system and HLA-matching in renal transplantation

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

Blood transfusions and HLA matching--an either/or situation in cadaveric renal transplantation

Cyclosporine-treated recipients of primary cadaver donor renal transplants had a one-year graft survival rate of 79% if they received pretransplant blood transfusions (n = 5308). The one-year survival rate for nontransfused recipients (n = 709) was significantly lower at 69% (P less than 0.001). The transfusion effect was larger in black recipients (a 17% difference) than in white recipients (5%). The effect was also larger in recipients of grafts poorly matched for HLA-A, B, -B, DR, or -DR antigens than in recipients of well-matched grafts. Transfusions did not significantly improve graft survival in recipients with zero or one HLA-A, B or -B, DR, or zero -DR-mismatched grafts. However, transfusions accounted for increases of 10%, 14%, and 17% in patients receiving grafts mismatched at 2, 3, or 4 HLA-B, DR antigens, respectively. Several factors including cyclosporine and HLA matching have contributed to improving graft survival rates in nontransfused recipients. Sensitization was noted in 20% of transfused patients awaiting primary renal transplants in Southern California, as compared with 10% in transplanted patients, suggesting a tendency to transplant nonsensitized patients. Of the sensitized patients, 75% were female. Based on these data, we suggest that high survival of primary kidney allografts in the cyclosporine era can best be maintained by the continued use of pretransplant transfusions for the majority of recipients--or, alternatively, by HLA matching for patients who are at higher risk of becoming sensitized.     

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.     

Dual kidney transplants from very old or very young donors: long-term outcomes and complications

The disparity between donors and the demand for organ transplants grows steadily. Annually, 4700 patients die on the kidney transplant waiting list in the United States. To increase utilization of deceased donor organs, we expanded our acceptable criteria to include very old (VO) or very young (VY) donors. We transplanted both such kidneys (dual transplant) into a single recipient and evaluated the long-term outcomes and complications. From July 2001 to December 2005, 16 patients (mean age 68, range 60-78) received dual kidneys from VO (mean age 72, range 60-79) donors and 6 patients (mean age 47, range 27-72) were transplanted from VY (mean age 17 months, range 2-36) donors. Seventy-four percent of these kidneys were imported after rejection by their local center due to low glomerular filtration rate (GFR) and extreme age. One- and 5-year patient survival rates were 100% and 88%, respectively. Death-censored 1- and 5-year graft survival rates for recipient of VO kidneys were 95% and 93%, and 66% and 50% for recipients of VY kidneys, respectively. Five-year graft survival rate for recipients of VO donor kidneys was 93% and was equal to the survival of standard deceased donor (SCD) kidney transplants (87%). The 5-year survival of dual transplants from VO donors was higher than expanded criteria deceased donor (ECD; P = .05). Over a mean follow-up of 66 ± 28 months, rejection rates were 10%, not statistically different than other groups. Of 22 dual transplants, four patients experienced urinary tract infections; three developed incisional subcutaneous seromas, and there were more urinary leaks compared to SCD (13.6% vs 2%, P = .002). The average 1- and 5-year estimated GFR (Cockcroft-Gault) was 57.4 and 54.6 mL/min, respectively. When properly placed in a single patient, such marginal organs are a valuable resource that offer comparable outcomes to SCD transplants and superior outcomes to ECD organs.     

Impact of human leukocyte antigen mismatching on outcomes of living donor liver transplantation for primary biliary cirrhosis.

Patient selection criteria of deceased donor liver transplantation for primary biliary cirrhosis (PBC) are almost completely established. The aim of this study was to establish selection criteria for both patients and donors of living donor liver transplantation (LDLT) for PBC. We used univariate and multivariate analyses to examine patient and donor characteristics of our first 50 cases of LDLT for PBC to elucidate factors that significantly impacted patient survival or disease recurrence after LDLT in the univariate and/or multivariate analyses. Multivariate analysis demonstrated that the presence of persistent ascites before LDLT, a higher number of human leukocyte antigen (HLA)-A, -B, and -DR mismatches between donor and recipient, and donor age >or=50 years were factors significantly associated with early posttransplant death. Independent risk factors for PBC recurrence after LDLT were a lower number of HLA mismatches between donor and recipient, and a lower average trough level of tacrolimus within 1 year after LDLT. Specifically, the lower the number of HLA-A, -B, and -DR mismatches or the average trough level of tacrolimus within 1 year after LDLT, the higher the possibility of developing a recurrence of PBC. In conclusion, the absence of persistent ascites before LDLT, a lower number of HLA-A, -B, and -DR mismatches between donor and recipient, and a younger donor (<50 years) are preferred for gaining acceptable survival outcomes for the transplant. However, a lower number of HLA-A, -B, and -DR mismatches between donor and recipient may be a risk factor for PBC recurrence.     

Human leukocyte antigen and adult living-donor liver transplantation outcomes: an analysis of the organ procurement and transplantation network database.

Human leukocyte antigen (HLA) compatibility has no clinically significant impact in cadaveric liver transplantation. Less is known regarding living-donor liver transplantation (LDLT). Our prior analysis of the Organ Procurement and Transplantation Network (OPTN) database suggested a higher graft failure rate in patients who underwent LDLT from donors with close HLA match. We further investigated the effect of HLA-A, -B, and -DR matching on 5-yr graft survival in adult LDLT by analyzing OPTN data regarding adult LDLT performed between 1998 and 2005. We evaluated associations between 5-yr graft survival and total, locus-specific, and haplotype match levels. Separate analyses were conducted for recipients with autoimmune (fulminant autoimmune hepatitis, cirrhosis secondary to autoimmune hepatitis, primary biliary cirrhosis, primary sclerosing cholangitis) or nonautoimmune liver disease. Multivariable Cox proportional hazard models were used to evaluate interactions and adjust for potential confounders. Among 631 patients with available donor/recipient HLA data, the degree of HLA match had no significant effect on 5-yr graft survival, even when analyzed separately in recipients with autoimmune vs. nonautoimmune liver disease. To be able to include all 1,838 adult LDLTs, we considered a first-degree related donor as substitute for a close HLA match. We found no difference in graft survival in related vs. unrelated pairs. In conclusion, our results show no detrimental impact of close HLA matching on graft survival in adult LDLT, including in recipients with underlying autoimmune liver disease.     

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.     

Kidney and Pancreas Transplantation in the United States, 1998–2007: Access for Patients with Diabetes and End-Stage Renal Disease

Although the number of candidates on the kidney transplant waiting list at year-end rose from 40 825 to 76 070 (86%) between 1998 and 2007, recent growth principally reflects increases in the number of patients in inactive status. The number of active patients increased by 'only' 4510 between 2002 and 2007, from 44 263 to 48 773. There were 6037 living donor and 10 082 deceased donor kidney transplants in 2007. Patient and allograft survival was best for recipients of living donor kidneys, least for expanded criteria donor (ECD) deceased donor kidneys, and intermediate for non-ECD deceased donor kidneys. The total number of pancreas transplants peaked at 1484 in 2004 and has since declined to 1331. Among pancreas recipients, those with simultaneous pancreas-kidney (SPK) transplants experienced the best pancreas graft survival rates: 86% at 1 year and 53% at 10 years. Between 1998 and 2006, among diabetic patients with end-stage renal disease (ESRD) who were under the age of 50 years, 23% of all and 62% of those waitlisted received a kidney-alone or SPK transplant. In contrast, 6% of diabetic patients aged 50–75 years with ESRD were transplanted, representing 46% of those waitlisted from this cohort. Access to kidney-alone or SPK transplantation varies widely by state.     

Antithymocyte globulin,pretransplant blood transfusion,and tissue typing in cadaver kidney transplantation

Three hundred forty-seven recipients of primary cadaver kidney transplants were analyzed in relation to ATG therapy, pretransplant transfusion, HLA-A, -B and -DR antigen matches, and level of PRA to the panel. Prophylactic ATG treatment increased transplant survival significantly when compared with the non-ATG group. The beneficial effect of pretransplant blood transfusions was not apparent when the recipients received prophylactic ATG treatment. No correlation was noted between HLA-A and -B antigen matches and transplant survival. There was no significant difference in the transplant survival between patients with zero DR antigen match kidneys and those with one DR antigen-match kidney. The number of transplants with two DR antigen-match kidneys was too small to be conclusive. The recipients in whom PRA did not develop despite pretransplant blood transfusions seemed to have better transplant survival than those in whom PRA did develop in response to blood transfusions.     

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.     

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.     

Simpler and equitable allocation of kidneys from postmortem donors primarily based on full HLA-DR compatibility

BACKGROUND: The introduction of human leukocyte antigen (HLA)-matching in nonliving kidney transplantation has resulted into a better graft outcome, but also in an increase of waiting time, especially for patients with rare HLA phenotypes. We addressed the question of the differential influence of HLA-DR-matching versus HLA-A,B in clinical kidney transplantation. METHODS: We used Kaplan-Meier product limit method to estimate survival rates, and Cox proportional hazard regression for the estimation of relative risks (Hazard-ratios) for different variables. RESULTS: A single center study (n=456 transplants, performed between 1985 and 1999) showed that full HLA-DR compatibility leads to a lower incidence of biopsy confirmed acute rejections in the first 180 posttransplantation days. These results were substantiated using the Eurotransplant database (n=39,205 transplants performed between 1985 and 2005) where graft survival in the full HLA-DR compatible group was significantly better than in the incompatible. An additional positive effect of HLA-A,B matching was only found in the full HLA-DR compatible group. In both studies, the introduction of a single HLA-DR incompatibility eliminates the HLA-A,B matching effect. CONCLUSIONS: We propose to allocate postmortem kidneys only to patients with full HLA-DR compatibility, and use HLA-A,B compatibility as an additional selection criterion. All patients, irrespective of their ethnic origin, will profit since the polymorphism of HLA-DR is by far lower than that of HLA-A,B. Excessive kidney travel and cold ischemia time will be significantly reduced.     

Inferior Early Posttransplant Outcomes for Recipients of Right Versus Left Deceased Donor Kidneys: An ANZDATA Registry Analysis

Anatomical differences between right and left kidneys could influence transplant outcome. We compared graft function and survival for left and right kidney recipients transplanted from the same deceased organ donor. Adult recipients of 4900 single kidneys procured from 2450 heart beating deceased donors in Australia and New Zealand from 1995 to 2009 were included in a paired analysis. Right kidneys were associated with more delayed graft function (DGF) (25 vs. 21% for left kidneys, p < 0.001) and, if not affected by DGF, a slower fall in serum creatinine. One‐year graft survival was lower for right kidneys (89.1 vs. 91.1% for left kidneys, p = 0.001), primarily attributed to surgical complications (66 versus 35 failures for left kidneys). Beyond the first posttransplant year, kidney side was not associated with eGFR, graft or patient survival. Receipt of a right kidney is a risk factor for inferior outcomes in the first year after transplantation. A higher incidence of surgical complications suggests the shorter right renal vein may be contributory. The higher susceptibility of right kidneys to injury should be considered in organ allocation.     

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.     

HLA-A and -B alleles in cornea donors as risk factors for graft rejection.

We determined the human leucocyte antigen (HLA)-A, -B and -DR allele frequencies in recipients and donors of 115 cornea transplants, for recipients who developed graft rejection and those who did not. No difference in HLA allele frequencies of the recipients was found. The frequencies of the HLA-A26, -B35 and -B44 alleles in cornea donors were increased in recipients who developed graft failure. The detrimental effect on corneal graft survival of these alleles was significant (p < 0.001). No such effect was observed in renal transplantation. Corneal graft survival was similar when one or two A26, B35 or B44 alleles were present on the donor cornea. The negative effect was similar in magnitude to the previously reported negative effect of an HLA-B locus match between donor and recipient. When both a B-locus match and an A26, B35 or B44 allele were present, the negative effect on graft survival was twice as strong, indicating that different immune mechanisms are responsible for these phenomena.     

Deceased donor renal transplantation--does side matter?

BACKGROUND: The aim of the present study was to determine whether the deceased donor kidney side (left or right kidney) was predictive of subsequent kidney transplant outcomes. METHODS: A retrospective analysis was undertaken of the left-right deceased donor kidney pairs transplanted into recipients with end-stage renal failure in Queensland between 1 April 1994 and 31 March 2004. RESULTS: A total of 201 left-right deceased donor kidney pairs were transplanted into 402 patients. The baseline characteristics of the recipients in the two groups were comparable, except that the patients receiving right kidneys had lower body mass indices and shorter cold ischaemic times. No differences were seen between the left and right kidney recipient groups with respect to operative duration (3.02 +/- 0.67 vs 3.12 +/- 0.72 h, P = 0.16), warm ischaemic time (0.62 +/- 0.18 vs 0.65 +/- 0.21, P = 0.09), delayed graft function (4 vs 6%, respectively, P = 0.26) or a composite vascular, haemorrhagic, ureteric and infective post-operative complication end-point (22 vs 22%, P = 0.90). Estimated glomerular filtration rates were almost identical at 1 month (52.7 +/- 39.6 vs 51.0 +/- 24.0 ml/min/1.73 m(2), P = 0.34) and remained comparable thereafter. Respective death-censored graft survival rates for left and right kidney recipients were 100 and 100% at 1 year, 99.4 and 96.4% at 3 years and 96.3 and 95.5% at 5 years, respectively (P = 0.67). CONCLUSIONS: Although left and right deceased donor kidneys present different operative challenges, the present results suggest that the probability of early post-operative complications, delayed graft function, impaired early and medium-term renal allograft function or death-censored graft failure is comparable between left and right kidney recipients.