Broader Geographic Sharing of Pediatric Donor Lungs Improves Pediatric Access to Transplant

US pediatric transplant candidates have limited access to lung transplant due to the small number of donors within current geographic boundaries, leading to assertions that the current lung allocation system does not adequately serve pediatric patients. We hypothesized that broader geographic sharing of pediatric (adolescent, 12–17 years; child, <12 years) donor lungs would increase pediatric candidate access to transplant. We used the thoracic simulated allocation model to simulate broader geographic sharing. Simulation 1 used current allocation rules. Simulation 2 offered adolescent donor lungs across a wider geographic area to adolescents. Simulation 3 offered child donor lungs across a wider geographic area to adolescents. Simulation 4 combined simulations 2 and 3. Simulation 5 prioritized adolescent donor lungs to children across a wider geographic area. Simulation 4 resulted in 461 adolescent transplants per 100 patient‐years on the waiting list (range 417–542), compared with 206 (range 180–228) under current rules. Simulation 5 resulted in 388 adolescent transplants per 100 patient‐years on the waiting list (range 348–418) and likely increased transplant rates for children. Adult transplant rates, waitlist mortality, and 1‐year posttransplant mortality were not adversely affected. Broader geographic sharing of pediatric donor lungs may increase pediatric candidate access to lung transplant.     

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.     

The new lung allocation system and its impact on waitlist characteristics and post-transplant outcomes

Historically, waiting time was the primary determinant of lung organ allocation in the United States. Under this system, waiting time grew progressively longer as the annual number of transplants reached a plateau, and every year, a considerable number of candidates died while waiting. In 2005, the lung allocation system changed; under the new system, priority for transplantation is determined by medical urgency and expected outcome. The lung allocation score is based on survival models that estimate waitlist and post-transplant survival, and reflects the net transplant benefit. Early evaluations of the new system indicate that waiting time has decreased, the total number of transplants has increased, waitlist mortality may be decreasing, and survival after transplantation remains unchanged. Over time, refinements in the lung allocation score will likely reduce waitlist mortality further and maintain or perhaps improve survival after transplantation.     

OPTN/SRTR 2019 Annual Data Report: Liver

This year was notable for changes to exception points determined by the geographic median allocation Model for End-Stage Liver Disease (MELD) and implementation of the National Liver Review Board, which took place on May 14, 2019. The national acuity circle liver distribution policy was also implemented but reverted to donor service area- and region-based boundaries after 1 week. In 2019, growth continued in the number of new waiting list registrations (12,767) and transplants performed (8,896), including living-donor transplants (524). Compared with 2018, living-donor liver transplants increased 31%. Women continued to have a lower deceased­donor transplant rate and a higher pretransplant mortality rate than men. The median waiting time for candidates with a MELD of 15-34 decreased, while the number of transplants performed for patients with exception points decreased. These changes may have been related to the policy changes that took effect in May 2019, which increased waiting list priority for candidates without exception status. Hepatitis C continued to decline as an indication for liver transplant, as the proportion of liver transplant recipients with alcohol-related liver disease and clinical profiles consistent with non-alcoholic steatohepatitis increased. Graft and patient survival have improved despite changing recipient demographics including older age, higher MELD, and higher prevalence of obesity and diabetes.     

Kidney transplantation from hepatitis B surface antigen-positive donors into hepatitis B surface antigen-positive recipients: preliminary findings

INTRODUCTION: The success of renal transplantation as a treatment for end-stage renal disease has created a chronic shortage of donor organs. We present our initial experience in transplanting kidneys from hepatitis B surface antigen (HbsAg)-positive donors into HbsAg-positive recipients. MATERIAL AND METHODS: From January 2002 to March 2004, 5 patients with end-stage renal disease, hepatitis B virus (HBV) infection, and HbsAg seropositivity underwent a kidney transplantation from a cadaveric HbsAg-positive donor. The median time on the waiting list was 8 months, compared with the median of 3 years on the national waiting list. RESULTS: One patient experienced an acute rejection; 1 patient had an increase in serum level of aspartate aminotransferase (AST)/alanine aminotransferase (ALT) with no signs of recurrence of hepatitis. Graft and patient survival at a median follow-up of 12 months was 100%. CONCLUSIONS: Although the number of patients is small and the follow-up is short, our results suggest that HbsAg-positive donors can be considered as an alternative donor source because their kidneys are allocated to the matched serology-positive recipients, shortening their time on the waiting list.     

Enhancing the Expanded Criteria Donor Policy as an Intervention to Improve Kidney Allocation: Is It Actually a ’Net‐Zero’ Model?

In the United States, relatively little progress has been made in recent years to improve the efficiency and effectiveness of deceased donor kidney allocation. Despite enactment of the Expanded Criteria Donor (ECD) Policy in 2002, known inequities and suboptimal utility of donated kidneys persist. In contrast with dialysis patients with shorter predicted life expectancies, those with longer predicted lifetimes can often improve their survival by waiting longer for a Standard Criteria Donor (SCD) kidney. Yet, a substantial fraction of these candidates accept ECD kidneys, often poorly HLA matched. Meanwhile, waitlist mortality continues to rise, particularly among older transplant candidates. Despite required consent processes for candidates to list for ECD kidneys, centers appear to interpret and implement ECD policy differently—some list candidates selectively while others list nearly their entire candidate pool. To ensure more efficient and effective implementation of ECD policy across centers, we advocate for (1) more oversight and guidance in directing patients to the ECD list who stand to benefit the most from receipt of an ECD kidney; and (2) enhanced transparency of center‐level ECD consent and listing practices. More uniform implementation of ECD policy could improve efficiency and effectiveness of deceased donor kidney allocation without deleteriously impacting equity.     

Kidney Transplant Outcomes for Prior Living Organ Donors

The Organ Procurement and Transplantation Network gives priority in kidney allocation to prior live organ donors who require a kidney transplant. In this study, we analyzed the effect of this policy on facilitating access to transplantation for prior donors who were wait-listed for kidney transplantation in the United States. Using 1:1 propensity score–matching methods, we assembled two matched cohorts. The first cohort consisted of prior organ donors and matched nondonors who were wait-listed during the years 1996–2010. The second cohort consisted of prior organ donors and matched nondonors who underwent deceased donor kidney transplantation. During the study period, there were 385,498 listings for kidney transplantation, 252 of which were prior donors. Most prior donors required dialysis by the time of listing (64% versus 69% among matched candidates; P=0.24). Compared with matched nondonors, prior donors had a higher rate of deceased donor transplant (85% versus 33%; P<0.001) and a lower median time to transplantation (145 versus 1607 days; P<0.001). Prior donors received higher-quality allografts (median kidney donor risk index 0.67 versus 0.90 for nondonors; P<0.001) and experienced lower post-transplant mortality (hazard ratio, 0.19; 95% confidence interval, 0.08 to 0.46; P<0.001) than matched nondonors. In conclusion, these data suggest that prior organ donors experience brief waiting time for kidney transplant and receive excellent-quality kidneys, but most need pretransplant dialysis. Individuals who are considering live organ donation should be provided with this information because this allocation priority will remain in place under the new US kidney allocation system.     

New French heart allocation system: Comparison with Eurotransplant and US allocation systems

Graft allocation rules for heart transplantation are necessary because of the shortage of heart donors, resulting in high waitlist mortality. The Agence de la biomédecine is the agency in charge of the organ allocation system in France. Assessment of the 2004 urgency‐based allocation system identified challenging limitations. A new system based on a score ranking all candidates was implemented in January 2018. In the revised system, medical urgency is defined according to candidate characteristics rather than the treatment modalities, and an interplay between urgency, donor‐recipient matching, and geographic sharing was introduced. In this article, we describe in detail the new allocation system and compare these allocation rules to Eurotransplant and US allocation policies.     

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.     

Regional sharing for adult status 1 candidates: reduction in waitlist mortality.

The intent of regional sharing for status 1 candidates is to promote timely access to donor livers. Presumably this decreases waitlist mortality. Little published data exists that supports this policy. Organ Procurement and Transplantation Network data was used to calculate region 4 and national adult waitlist death and transplant rates 4 yr prior to (period A) and after (period B) implementation of the sharing agreement in July 1999. Death and transplant rates were calculated using a competing risk analysis. Regional sharing resulted in a reduction in adult status 1 waitlist death rate and an increase in transplant rate for region 4 candidates at 7 and 14 days (P > 0.05) without a change in the death rate at 90 days for the non-status 1 candidates. National data showed a significant increase in transplant rate at 7 days and reduction in waitlist death rate at 14 days after listing (P < 0.05). Status 1 waiting time was decreased from 10 to 3 days (P < 0.05). Adult patient survival was not significantly different between the periods. In conclusion, regional sharing for status 1 candidates results in an increased transplant rate and a reduction in waitlist mortality. Sharing did not impact waitlist mortality for non-status 1 candidates.     

Deceased donors as nondirected donors in kidney paired donation

As proof of concept, we simulate a revised kidney allocation system that includes deceased donor (DD) kidneys as chain-initiating kidneys (DD-CIK) in a kidney paired donation pool (KPDP), and estimate potential increases in number of transplants. We consider chains of length 2 in which the DD-CIK gives to a candidate in the KPDP, and that candidate's incompatible donor donates to theDD waitlist. In simulations, we vary initial pool size, arrival rates of candidate/donor pairs and (living) nondirected donors (NDDs), and delay time from entry to the KPDP until a candidate is eligible to receive a DD-CIK. Using data on candidate/donor pairs and NDDs from the Alliance for Paired Kidney Donation, and the actual DDs from the Scientific Registry of Transplant Recipients (SRTR) data, simulations extend over 2 years. With an initial pool of 400, respective candidate and NDD arrival rates of 2 per day and 3 per month, and delay times for access to DD-CIK of 6 months or less, including DD-CIKs increases the number of transplants by at least 447 over 2 years, and greatly reduces waiting times of KPDP candidates. Potential effects on waitlist candidates are discussed as are policy and ethical issues.     

Primum non nocere: avoiding harm to vulnerable wait list candidates in an indirect kidney exchange.

BACKGROUND: One proposal to increase kidney transplantation is to exchange kidneys between pairs of ABO-incompatible (or cross-match-incompatible) living donors and their recipients. One variation that has greater potential exchanges living donor kidneys for cadaveric donor kidneys (indirect exchanges). A primary concern with indirect exchanges is the potential to disadvantage blood group O wait list candidates. Using wait list modeling, we examine whether this proposal would disadvantage cadaveric kidney blood group O wait list candidates, and present an approach for neutralizing these negative effects. METHODS: A probability model estimated the total number and blood type frequencies of donor-recipient pairs that would participate in indirect exchanges. A supply-to-demand model for the cadaveric kidney wait list estimated the mean wait time under different allocation policies and donor selection mechanisms for candidates on the wait list classified according to the candidates' race and blood type. RESULTS: Indirect exchanges will reduce the mean wait time for cadaveric kidney wait list candidates. The mean wait time of blood group O cadaveric kidney wait list candidates increases when the participating living donors self-select and when kidney allocation is determined by efficiency. This is neutralized when the transplant team preferentially selects blood group O living donors and cadaveric kidney allocation is determined by need. CONCLUSION: Indirect exchange programs will significantly shorten the wait times for cadaveric kidney wait list candidates. The wait times of blood group O candidates will not be affected adversely if blood group O living donors are selected preferentially and if allocation is based on need.     

Mortality among solid organ waitlist candidates during COVID-19 in the United States

We examined the effects of COVID-19 on solid organ waiting list mortality in the United States and compared effects across patient demographics (e.g., race, age, and sex) and donation service areas. Three separate piecewise exponential survival models estimated for each solid organ the overall, demographic-specific, and donation service area-specific differences in the hazard of waitlist mortality before and after the national emergency declaration on March 13, 2020. Kidney waiting list mortality was higher after than before the national emergency (adjusted hazard ratio [aHR], 1.37; 95% CI, 1.23–1.52). The hazard of waitlist mortality was not significantly different before and after COVID-19 for liver (aHR, 0.94), pancreas (aHR, 1.01), lung (aHR, 1.00), and heart (aHR, 0.94). Kidney candidates had notable variability in differences across donation service areas (aHRs, New York City, 2.52; New Jersey, 1.84; and Michigan, 1.56). The only demographic group with increased waiting list mortality were Blacks versus Whites (aHR, 1.41; 95% CI, 1.07–1.86) for kidney candidates. The first 10 weeks after the declaration of a national emergency had a heterogeneous effect on waitlist mortality rate, varying by geography and ethnicity. This heterogeneity will complicate comparisons of transplant program performance during COVID-19.     

Liver and Intestine Transplantation in the United States 1998–2007

Liver transplantation numbers in the United States remained constant from 2004 to 2007, while the number of waiting list candidates has trended down. In 2007, the waiting list was at its smallest since 1999, with adults ≥50 years representing the majority of candidates. Noncholestatic cirrhosis was most commonly diagnosed. Most age groups had decreased waiting list death rates; however, children <1 year had the highest death rate. Use of liver allografts from donation after cardiac death (DCD) donors increased in 2007. Model for end-stage liver disease (MELD)/pediatric model for end-stage liver disease (PELD) scores have changed very little since 2002, with MELD/PELD <15 accounting for 75% of the waiting list. Over the same period, the number of transplants for MELD/PELD <15 decreased from 16.4% to 9.8%. Hepatocellular carcinoma exceptions increased slightly. The intestine transplantation waiting list decreased from 2006, with the majority of candidates being children <5 years old. Death rates improved, but remain unacceptably high. Policy changes have been implemented to improve allocation and recovery of intestine grafts to positively impact mortality. In addition to evaluating trends in liver and intestine transplantation, we review in depth, issues related to organ acceptance rates, DCD, living donor transplantation and MELD/PELD exceptions.     

Liver and intestine transplantation: summary analysis, 1994–2003

With nearly two years of data available since the inception of the MELD and PELD allocation system, this article examines national OPTN/SRTR data to describe trends in waiting list composition, waiting list mortality, transplant rates, and patient and graft outcomes for liver transplantation.
Following a 6% reduction in the size of the waiting list after MELD was implemented in 2002, the number of patients on the waiting list grew by 2% from 2002 to 2003, while the number of liver transplants increased by 6%. The overall death rate while on the liver waiting list has decreased from 225 deaths per 1,000 patient years in 1994 to 124 deaths in 2003. As with the waiting list death rates, post-transplant death rates have also decreased over the past decade. Unadjusted one-year patient survival was lower for older donor age groups (88% for donors aged 18–34, 87% for donors aged 35–49, 85% for donors aged 50-64); a similar trend was observed at three and five years following transplantation.
Intestine transplantation is performed with slowly increasing frequency and success. Early graft losses and rejection rates have changed little since 1994, but rejection is easier to control and long-term survival is improving.     

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.     

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.     

Proceedings of the AST heart allocation meeting at the American Transplant Congress,Philadelphia, Pennsylvania,May 4, 2015

Ensuring fair and equitable allocation of donor hearts in the US is the charge of the Organ Procurement and Transplantation Network (OPTN). However, the recent increase of candidates waiting without a corresponding increase in available donors, higher waitlist mortality rates in higher status patients, the presence of disadvantaged subgroups, and the changing management of heart failure patients with increased VAD usage, has necessitated review of allocation policy. Therefore, the Heart Subcommittee of the OPTN/UNOS Thoracic Committee is exploring a further‐tiered allocation system, devising a “straw man” model as a starting point for modeling analyses and public discussion. On May 4, 2015, an American Society of Transplantation (AST)‐endorsed forum to discuss these potential proposed changes took place. Attendees included 41 people, mostly highly experienced transplant cardiologists and cardiothoracic surgeons, representing 19 heart transplant centers across the US, UNOS, and the Scientific Registry of Transplant Recipients (SRTR). There was unanimous agreement that the potential proposed policy will require careful wording to avoid ambiguity and “gaming” of the system, and strong support for abolishment of local organ sharing in favor of geographic sharing. However, contention existed concerning the appropriate prioritization levels of ECMO, temporary VAD/TAH patients as well as the 30‐day LVAD listing.     

Managing highly sensitized renal transplant candidates in the era of kidney paired donation and the new kidney allocation system: Is there still a role for desensitization?

Kidney paired donation (KPD) and the new kidney allocation system (KAS) in the United States have led to improved transplantation rates for highly sensitized candidates. We aimed to assess the potential need for other approaches to improve the transplantation rate of highly sensitized candidates such as desensitization. Using the UNOS STAR file, we analyzed transplant rates in a prevalent active waiting‐list cohort as of June 1, 2016, followed for 1 year. The overall transplantation rate was 18.9% (11 129/58769). However, only 9.7% (213/2204) of candidates with a calculated panel reactive antibody ≥99.9% received a transplant, and highly sensitized candidates were less likely to receive a living donor transplant. Among candidates with a CPRA ≥ 99.5% (ie. 100%), only 2.5% of transplants were from living donors (13 total, 7 from KPD). Nearly 4 years after KAS (6/30/2018), 1791 actively wait‐listed candidates had a CPRA of ≥99.9% and 34.6% (620/1791) of these had ≥5 years of waiting time. Thus, despite KPD and KAS, many sensitized candidates have not been transplanted even with prolonged waiting time. We conclude that candidates with a CPRA ≥ 99.9% and sensitized candidates with an incompatible living donor and prolonged waiting time may benefit from desensitization to improve their ability to receive a transplant.     

Variables of importance in the Scientific Registry of Transplant Recipients database predictive of heart transplant waitlist mortality

The prelisting variables essential for creating an accurate heart transplant allocation score based on survival are unknown. To identify these we studied mortality of adults on the active heart transplant waiting list in the Scientific Registry of Transplant Recipients database from January 1, 2004 to August 31, 2015. There were 33 069 candidates awaiting heart transplantation: 7681 UNOS Status 1A, 13 027 Status 1B, and 12 361 Status 2. During a median waitlist follow‐up of 4.3 months, 5514 candidates died. Variables of importance for waitlist mortality were identified by machine learning using Random Survival Forests. Strong correlates predicting survival were estimated glomerular filtration rate (eGFR), serum albumin, extracorporeal membrane oxygenation, ventricular assist device, mechanical ventilation, peak oxygen capacity, hemodynamics, inotrope support, and type of heart disease with less predictive variables including antiarrhythmic agents, history of stroke, vascular disease, prior malignancy, and prior tobacco use. Complex interactions were identified such as an additive risk in mortality based on renal function and serum albumin, and sex‐differences in mortality when eGFR >40 mL/min/1.73 m. Most predictive variables for waitlist mortality are in the current tiered allocation system except for eGFR and serum albumin which have an additive risk and complex interactions.