The Expanded Criteria Donor Policy: An Evaluation of Program Objectives and Indirect Ramifications

The expanded criteria donor (ECD) policy was formalized in 2002, which defined higher-risk deceased donor kidneys recovered for transplantation. There has not been a comprehensive examination of the impact of policy on the allocation of ECD kidneys, waiting times for transplant, center listing patterns or human leukocyte antigen (HLA) matching. We examined transplant candidates from 1998 to 2004 utilizing a national database. We constructed models to assess alterations in recipient characteristics of ECD kidneys and trends in waiting time and cold ischemia time (CIT) associated with policy. We also evaluated the impact of the proportion of center candidate listings for ECD kidneys on waiting times. Elderly recipients were more likely to receive ECDs following policy (odds ratio = 1.36, p < 0.01). There was no association of decreased CIT or pretransplant dialysis time while increasing HLA mismatching with policy inception. Over one quarter of centers listed < 20% of candidates for ECDs, while an additional quarter of centers listed > 90%. Only centers with selective listing for ECDs offered reduced waiting times to ECD recipients. The ECD policy demonstrates potential to achieve certain ascribed goals; however, the full impact of the program, reaching all transplant candidates, may only be achieved once ECD listing patterns are recommended and adopted accordingly.     

For the many: permitting deceased donor kidney transplantation across low‐titre blood group antibodies can reduce wait times for blood group B recipients,and improve the overall number of 000MM transplants ‐ a multicentre observational cohort study

Blood group O or B recipients wait longer for a kidney transplant. We studied the distribution of anti‐ABO blood group antibody titres in patients awaiting a kidney transplant, and modelled the effect of altering the UK National Kidney Allocation Scheme to allow for patients with ‘LOW’ titres (≤1:8, ≤3 dilutions) to receive a deceased donor ABOi (ddABOi) transplant. In a prospective study of 239 adult patients on the waiting list for a transplant in 2 UK centres, ABO‐antibody titres (anti‐A and anti‐B) were measured. Based on the proportions of ‘LOW’ anti‐A or anti‐B antibodies, four simulations were performed to model the current allocation rules compared with variations allowing ddABOi allocation under various conditions of blood group, HLA matching, and waiting time. The simulations permitting ddABOi resulted in more blood group B recipients being transplanted, with median waiting time reduced for this group of recipients, and more equitable waiting times across blood groups. Additionally, permitting ddABOi resulted in greater numbers of 000MM allocations overall in compatible transplants under modelled conditions. Changing allocation in the UK to permit ddABOi in patients with ‘LOW’ titres would not change the total number of transplants, but redistributes allocation more equitably amongst blood groups, altering waiting times accordingly.     

The national impact of the 1995 changes to the UNOS renal allocation system

In 1995, changes in the United Network for Organ Sharing (UNOS) renal allocation policies expanded the mandatory share (MS) category to include zero antigen mismatches (0 mm), increased points for waiting time and for pediatric status, and eliminated points for certain HLA match grades. Data from the national scientific registry on 11344 and 11652 renal allograft recipients were analyzed for periods prior to and following the policy changes to assess the impact on organ allocation. The overall frequency of transplants going to non-Caucasians increased between the study periods, but the increase was significant only in the MS category. The proportion of MS transplants nearly doubled for African-Americans, increasing from 5.5% to 10.5%, while Hispanic/Latino recipients experienced a smaller increase, from 7.2% to 8.9%. The increased numbers of MS transplants clearly resulted from the inclusion of the 0 mm in the MS category. Among the NMS transplants, the average number of mismatched HLA antigens increased slightly. No effect of the additional points for waiting time was observed among recipients of non-mandatory share (NMS) transplants. The increase in mean waiting time until transplant for NMS recipients was attributable to the growth in the size of the waiting list. In contrast, there was a significant increase in mean waiting time for MS recipients. There were no significant changes in the proportions of sensitized or pediatric recipients between the study periods. In conclusion, only the changes in the MS policies appeared to have any significant effect on renal allocation. Further efforts will be required to address increasing allocation to patients disadvantaged by sensitization and/or prolonged waiting times.     

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.     

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).     

On the allocation of cardiac allografts from blood group-O donors

An organ allocation policy, in which hearts from blood group-O donors are used to transplant recipients with other blood groups (ABO-compatible, non-identical transplantations), may affect blood group-O patients on the waiting list. We investigated how blood group affiliation influences potential recipients on the waiting list. In the case of patients with blood group O, fewer patients were transplanted, waiting list mortality was higher and waiting time to transplantation was longer. Patients with blood group O awaiting cardiac transplantation are affected considerably by an organ allocation policy in which ABO-compatible, non-identical transplantations are performed.     

On the Allocation of Cardiac Allografts from Blood Group-O Donors

An organ allocation policy, in which hearts from blood group-O donors are used to transplant recipients with other blood groups (ABO-compatible, non-identical transplantations), may affect blood group-O patients on the waiting list. We investigated how blood group affiliation influences potential recipients on the waiting list. In the case of patients with blood group O, fewer patients were transplanted, waiting list mortality was higher and waiting time to transplantation was longer. Patients with blood group O awaiting cardiac transplantation are affected considerably by an organ allocation policy in which ABO-compatible, non-identical transplantations are performed.     

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.     

Repeated kidney re-transplantation—the Eurotransplant experience: a retrospective multicenter outcome analysis

In Eurotransplant kidney allocation system (ETKAS), candidates can be considered unlimitedly for repeated re-transplantation. Data on outcome and benefit are indeterminate. We performed a retrospective 15-year patient and graft outcome data analysis from 1464 recipients of a third or fourth or higher sequential deceased donor renal transplantation (DDRT) from 42 transplant centers. Repeated re-DDRT recipients were younger (mean 43.0 vs. 50.2 years) compared to first DDRT recipients. They received grafts with more favorable HLA matches (89.0% vs. 84.5%) but thereby no statistically significant improvement of patient and graft outcome was found as comparatively demonstrated in 1st DDRT. In the multivariate modeling accounting for confounding factors, mortality and graft loss after 3rd and ≥4th DDRT (P < 0.001 each) and death with functioning graft (DwFG) after 3rd DDRT (P = 0.001) were higher as compared to 1st DDRT. The incidence of primary nonfunction (PNF) was also significantly higher in re-DDRT (12.7%) than in 1st DDRT (7.1%; P < 0.001). Facing organ shortage, increasing waiting time, and considerable mortality on dialysis, we question the current policy of repeated re-DDRT. The data from this survey propose better HLA matching in first DDRT and second DDRT and careful selection of candidates, especially for ≥4th DDRT.     

Association Between Waiting Times for Kidney Transplantation and Rates of Live Donation

A deceased donor (DD) allocation system incorporating net life survival benefit has been proposed. In this system, many kidneys will be shifted to younger recipients, thereby decreasing their waiting times. The goal of this study was to determine the potential effects of altering waiting times on the likelihood of live donor kidney transplantation (LDKT). We analyzed 93,727 waiting list candidates to determine the association of various patient factors with likelihood of LDKT. The proportion of patients receiving LDKT was compared by the median DD waiting time at that patient's transplant center for someone of that patient's age category and race. LDKT was consistently higher as waiting times became longer. After adjusting for all other factors associated with likelihood of LDKT, waiting time remained a significant, independent predictor. Patients with the longest DD waiting times had 2.3-fold higher odds of LDKT (95% CI 2.11-2.58, p < 0.001). In planning the new DD allocation policy, we must account for resulting alterations in LDKT. It is possible that shifting DD kidneys to younger recipients may decrease LDKT or shift it to older recipients, net effects not consistent with the goal of net life survival benefit.     

Efficiency is a legitimate consideration in equitable distribution of cadaveric transplants: development of an efficiency-equality model of equity

It is proposed that equity is a trade-off, or compromise, between equality and efficiency. The kidney transplant allocation algorithm currently used in the United Kingdom (NAT) was tested in the efficiency-equity model. In an exercise of 2000 past UK donors and a dynamic waiting list of 5000 potential recipients, 4000 transplants were allocated according either by NAT, by equal allocation (EQ) (a lottery), or by efficiency (EF). Diabetic recipients received 7.4% of transplants in NAT, 8.6% in EQ, and 0% in EF; paediatric recipients received 6.8% in NAT, 0.6% in EQ, and 0.7% in EF model. For HLA matching, there were 77.9% favourable or 000 matches in NAT, 3.0% in EQ, and 53.1% in EF. Predicted survival showed better outcomes in EF versus NAT (P < .0001) and in NAT versus EQ (P = .05). The NAT allocation system favours paediatric recipients and does not deny diabetics the chance of a transplant, broadly in line with published public and professional opinions. The NAT scheme achieves better HLA matching than the EF model, and this suggests that the rationale for allocation based primarily on HLA matching could be reexamined.     

Comparison of time on the deceased donor kidney waitlist versus time on the kidney paired donation registry in the Australian program

In the Australian kidney paired donation (KPD) program matching is based on acceptable mismatches, whereas deceased donor waitlist (DDWL) patients are allocated kidneys based on HLA antigen matching rules. Herein, we compared waiting time for a KPD match to the waiting time on the DDWL and the occurrence of matching in the DDWL for patients who were registered in both programs. Data on first dialysis, matches on the DDWL, KPD program entry, matches and transplant dates were assessed in 26 KPD recipients of the Australian program. There were 22 recipients who were listed in the DDWL and received kidney transplants by KPD. Time on dialysis until KPD transplantation was 808 ± 646 days. Eleven patients had never been matched with a deceased donor (waiting time 345 ± 237 days) and 11 had been matched on average 3 ± 5 times (waiting time 1227 ± 615 days, P < 0.0001 vs. never matched), but did not progress to transplantation because of positive crossmatch or class II donor‐specific antibody. Mean time from registration in the KPD program until kidney transplantation was 153 ± 92 days (P < 0.0001 vs. DDWL). KPD allocation using the acceptable mismatch approach is effective in identifying suitable live donors for some recipients within a relatively short time‐frame.     

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.     

Transplanting Kidneys Without Points for HLA‐B Matching: Consequences of the Policy Change

In 2003, the US kidney allocation system was changed to eliminate priority for HLA‐B similarity. We report outcomes from before and after this change using data from the Scientific Registry of Transplant Recipients (SRTR). Analyses were based on 108 701 solitary deceased donor kidney recipients during the 6 years before and after the policy change. Racial/ethnic distributions of recipients in the two periods were compared (chi‐square); graft failures were analyzed using Cox models. In the 6 years before and after the policy change, the overall number of deceased donor transplants rose 23%, with a larger increase for minorities (40%) and a smaller increase for non‐Hispanic whites (whites) (8%). The increase in the proportion of transplants for non‐whites versus whites was highly significant (p < 0.0001). Two‐year graft survival improved for all racial/ethnic groups after implementation of this new policy. Findings confirmed prior SRTR predictions. Following elimination of allocation priority for HLA‐B similarity, the deficit in transplantation rates among minorities compared with that for whites was reduced but not eliminated; furthermore, there was no adverse effect on graft survival.     

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.     

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.     

Current Kidney Allocation Rules and Their Impact on a Pediatric Transplant Center

In 2005, kidney allocation rules in the United States were updated to enhance access to kidneys from young adult deceased donors (DDs) for pediatric recipients. We studied how this rule change affected transplant activity at our pediatric center. We retrospectively compared kidney transplant activity at our center since the rule change (until December 31, 2007) to before the change (n = 36 each), focusing on those recipients directly affected by it, that is, younger than 18 years. There were no significant differences in recipients' age, gender or ethnicity before versus after the rule change. Percentages of preemptive transplants and retransplants were similar in both groups, as was the percentage of sensitized patients. There was a significant decrease in overall, but not DD, mean donor age. Mean wait time for DD kidneys decreased for pediatric recipients. Increases were found in percentage of DD transplants and in mean HLA mismatches after the rule change. Patient and short-term graft survival were not significantly different. These data suggest that the allocation rule change was not only followed by improvement in overall access to kidney transplantation for children, but also by decreases in living donor transplants and HLA matching. Larger studies are needed to evaluate the long-term impact of the change.     

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.     

The heart-allocation simulation model: a tool for comparison of transplantation allocation policies

BACKGROUND: Numerous studies have investigated prognostic factors for the survival of transplant candidates waiting for a donor organ, but little is known about the impact of allocation policies on waiting list outcome. Simulation models would allow a comparison of different policies for allocating donor hearts on pretransplant outcome. METHODS: A model was built for the Eurotransplant waiting list for heart transplantation. Survival and delisting distributions were estimated from the Eurotransplant transplant candidate inflow between 1995 and 2000 (n=7,142). Other characteristics were obtained directly from the transplant candidate inflow of 1999 and 2000 (n=2,097) and the donor organs of 1998 and 1999 (n=1,520). Overall and subgroup waiting list mortality were estimated for allocation policies differing by ABO blood group, border, and clinical profile rules. RESULTS: The model estimated that international organ exchange reduces waiting list mortality in the different countries by 1.9% to 12.4%. An allocation policy incorporating the initial clinical profile of the transplant candidates further reduced waiting list mortality by 1.7%. Changing ABO rules toward identical matching yielded a slightly more equitable survival for the different groups, without an overall effect on mortality. The best possible allocation policy is the policy where organs are allocated to patients that are at highest risk of dying, and withholding organs from patients that would eventually delist because of improvement. CONCLUSIONS: Patients benefit from international organ exchange and by a heart allocation scheme based on clinical profiles. Timely delisting of patients who are-temporarily-too well for transplantation is the best waiting list policy.