The impact of donor age and recipient age on clinical course and immune response after organ transplantation

Organ shortage and increasing numbers of older patients on the waiting list represent major challenges in organ transplantation. As a consequence, older donor organs are increasingly used and preferentially allocated to elderly recipients. However, knowledge on donor age– and recipient age–dependent immune responses is limited. We reviewed the impact of donor age and recipient age on clinical outcomes. An increased immunogenicity of older grafts and an altered immune response of elderly recipients may require age-specific immunosuppression. Age-related immune responses may also impact current preclinical tolerance protocols.     

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.     

Pediatric transplantation, 1994–2003

This article uses OPTN/SRTR data to review trends in pediatric transplantation over the last decade. In 2003, children younger than 18 made up 3% of the 82,885 candidates for organ transplantation and 7% of the 25,469 organ transplant recipients. Children accounted for 14% of the 6,455 deceased organ donors. Pediatric organ transplant recipients differ from their adult counterparts in several important aspects, including the underlying etiology of organ failure, the complexity of the surgical procedures, the pharmacokinetic properties of common immunosuppressants, the immune response following transplantation, the number and degree of comorbid conditions, and the susceptibility to post-transplant complications, especially infectious diseases. Specialized pediatric organ transplant programs have been developed to address these special problems, The transplant community has responded to the particular needs of children and has provided them special consideration in the allocation of deceased donor organs. As a result of these programs and protocols, children are now frequently the most successful recipients of organ transplantation; their outcomes following kidney, liver, and heart transplantation rank among the best. This article demonstrates that substantial improvement is needed in several areas: adolescent outcomes, outcomes following intestine transplants, and waiting list mortality among pediatric heart and lung candidates,     

Liver transplant recipient selection: MELD vs. clinical judgment.

Minimization of death while waiting for liver transplantation involves accurate prioritization according to clinical status and appropriate allocation of donor livers. Clinical judgment in the Liver Transplant Unit Victoria (LTUV) was compared with Model for End-Stage Liver Disease (MELD) in a retrospective analysis of the LTUV database over the 2-year period August 1, 2002, through July 31, 2004. A total of 1,118 prioritization decisions occurred. Decisions were concordant in 758 (68%), comparing priorities assigned by clinical judgment with those assigned by MELD, P < 0.01. A total of 263 allocation decisions occurred. Decisions were concordant in 190 (72%) and 203 (77%) of the cases, comparing donor liver allocation with prioritization by MELD and clinical judgment, respectively. Of the 52 patients allocated a liver, only 23 would have been allocated on the basis of MELD while 29 had been prioritized on the waiting list in the week prior to transplantation. A total of 10 patients died on the waiting list in the 2-year period (annual adult waiting list mortality is 9.3%). Patients who subsequently died waiting were 3 times as likely to be prioritized by MELD as clinical judgment (29% vs. 9%, respectively). One half (3 of 6) of the patients who could have received a donor liver but who died waiting would have been allocated the organ on the basis of MELD. In conclusion, an allocation process based on MELD rather than clinical judgment would significantly alter organ allocation in Australia and may reduce waiting list mortality.     

Direction of the Organ Procurement and Transplantation Network and United Network for Organ Sharing Regarding the Oversight of Live Donor Transplantation and Solicitation for Organs

The Organ Procurement and Transplantation Network (OPTN) operated by United Network for Organ Sharing (UNOS) has taken recent steps to address public solicitation for organ donors and its oversight of live donor transplantation. This report provides the direction of the OPTN regarding deceased donor solicitation. The OPTN has authority under federal law to equitably allocate deceased donor organs within a single national network based upon medical criteria, not upon one's social or economic ability to utilize resources not available to all on the waiting list. The OPTN makes a distinction between solicitations for a live donor organ versus solicitations for directed donation of deceased organs. As to live donor solicitation, the OPTN cannot regulate or restrict ways relationships are developed in our society, nor does it seek to do so. OPTN members have a responsibility of helping protect potential recipients from hazards that can arise from public appeals for live donor organs. Oversight and support of the OPTN for live donor transplantation is now detailed by improving the reporting of live donor follow-up, by providing a mechanism for facilitating anonymous live kidney donation, and by providing information for potential live kidney donors via the UNOS Transplant Living website.     

Impact of parenteral nutrition-associated liver disease on intestinal transplant waitlist dynamics

BACKGROUND: United Network for Organ Sharing (UNOS) reports indicate that waiting list mortality for intestinal transplant candidates greatly exceeds that for all other organ transplant candidates. But United Network for Organ Sharing outcomes reports have not routinely distinguished between the intestine candidate subgroups that are listed only for an intestine and those that are also listed for a liver. STUDY DESIGN: Data were obtained by request from the collaborative Organ Procurement and Transplantation Network (United Network for Organ Sharing)/Scientific Registry of Transplant Recipients (University Research and Education Association) database. Waiting list data for intestinal transplant recipients from 1995 to 2004 were divided into those candidates listed for only an intestine and those listed for both an intestine and a liver. Additional data concerning overall waiting list outcomes and posttransplant survival rates stratified into pediatric and adult subsets were also obtained and analyzed. RESULTS: The overall number of candidates on the intestinal transplant waiting list has increased steadily since 1995 and, consistently, the majority of candidates have also been listed for a liver. This subset was found to have both a higher relative risk of dying while awaiting transplantation and lower relative odds of receiving transplants. In addition, parenteral nutrition-associated liver disease is a major problem across all age groups, as evidenced by the combined liver and intestine listings that compose the majority of both adult and pediatric waiting list populations. Posttransplant survival data were found to be superior for isolated intestine recipients compared with liver-intestine recipients. CONCLUSIONS: The preponderance of dual listings and their associated inferior outcomes, before and after transplantation, has skewed overall intestinal transplant outcomes. Because progression of parenteral nutrition-associated liver disease can be insidious, and recognition of irreversibility is often difficult, intestine-only transplants should be considered early for high-risk patients before parenteral nutrition-associated liver disease progression mandates inclusion of a liver graft also.     

Changes in the Organ Procurement System in South Korea: Effects on Brain-Dead Donor Numbers

In Korea, the Organ Transplantation Act came into effect in 2000, establishing the Korean Network for Organ Sharing (KONOS) with centralized authority for organ procurement as well as for approval of donors and recipients to ensure fair organ allocation. However, the number of brain-dead donors decreased sharply, and the organ allocation system proved inefficient. The government revised the Organ Transplantation Act in August 2002, introducing an incentive system. If a transplantation hospital formed a Committee for Brain Death Evaluation and a Hospital Organ Procurement Organization, it could receive a kidney from a brain dead-donor as an incentive to foster organ procurement regardless of the KONOS wait list. The government also launched a pilot brain-dead donor registry program to strengthen Hospital Organ Procurement Organization activity. If local hospitals collaborated with specialized hospitals in organ procurement, local hospitals obtained financial incentives. But because the organ shortage problem has not been resolved, the government has proposed four initiatives: first, broadening the incentive system, which makes it possible to give each specialized hospital a choice of one of eight organs from each donor as an incentive; second, development of an Independent Organ Procurement Organization; third introduction of an opt-out system; and last, improvement of the Committee for Brain Death Evaluation system. It is uncertain which initiatives will be adopted, but changes in organ procurement systems are nonetheless considered a key to solve the organ shortage problem in Korea.     

Evidence‐based development of liver allocation: a review

Liver transplantation has undergone a rapid evolution from a high‐risk experimental procedure to a mainstream therapy for thousands of patients with a wide range of hepatic diseases. Its increasing success has been accompanied by progressive imbalance between organ donor supply and the patients who might benefit. Where demand outstrips supply in transplantation, a system of organ allocation is inevitably required to make the wisest use of the available, but scarce, organs. Early attempts to rationally allocate donor livers were particularly hampered by lack of available and suitable data, leading to imperfect solutions that created or exacerbated inequities in the system. The advent and maturation of evidence‐based predictors of waiting list mortality risk led to more objective criteria for liver allocation, aided by the increasing availability of data on large numbers of patients. Until now, the vast majority of allocation systems for liver transplantation have relied on estimation of waiting list mortality. Evidence‐based allocation systems that incorporate measures of post‐transplant outcomes are conceptually attractive and these transplant benefit‐based allocation systems have been developed, modeled, and subjected to computer simulation. Future implementations of benefit‐based liver allocation await continued refinement and additional debate in the transplant community.     

Thirteen years of the Thai red cross organ donation centre

The Thai Red Cross Organ Donation Centre was founded more than 13 years ago. Its primary roles are to promote organ donation, recipient registration, organ allocation and coordination of procurement. METHOD: This was a retrospective analysis of data from the Thai Red Cross Organ Donation Centre from February 1, 1994, to October 31, 2007. RESULTS: There were 450,069 people registered as potential donors. Over the past 6 years, the average new registration was 35,000 people per year. There were 791 deceased organ donors, yielding 1786 organs and 1062 tissues for transplantation. They comprised 1414 kidneys, 242 livers, 125 thoracic organs, 4 liver-kidneys, 1 pancreas-kidneys, 652 corneas, 370 heart valves, 36 bones, 3 blood vessels, and 1 skin. In the early period, each donor provided about three organs/tissues for transplantation. Now, each organ donor can provide 3.6 organs/tissues for transplantation. DISCUSSION: At present, the Thai Red Cross Organ Donation Centre is also authorized by The Medical Council of Thailand to oversee transplant practices in the country. There is a tendency for an increase in organ and tissue donations, although the numbers of waiting list patients is out of proportion to those of actual donors. CONCLUSION: Over the 13-year period of the Thai Red Cross Organ Donation Centre, there were 791 deceased organ donors who provided 2809 organ/tissues for transplantation.     

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.     

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.     

Thoracic organ transplantation in the United States, 1994–2003

Using OPTN/SRTR data, this article reviews the state of thoracic organ transplantation in 2003 and the previous decade. Time spent on the heart waiting list has increased significantly over the last decade. The percentage of patients awaiting heart transplantation for >2 years increased from 23% in 1994 to 49% by 2003. However, there has been a general decline in heart waiting list death rates over the decade. In 2003, the lung transplant waiting list reached a record high of 3,836 registrants, up slightly from 2002 and more than threefold since 1994. One-year patient survival for those receiving lungs in 2002 was 82%, a statistically significant improvement from 2001 (78%). The number of patients awaiting a heart-lung transplant, declining since 1998, reached 189 in 2003. Adjusted patient survival for heart-lung recipients is consistently worse than the corresponding rate for isolated lung recipients, primarily due to worse outcomes for heart-lung recipients with congenital heart disease. A new lung allocation system, approved in June 2004, derives from the survival benefit of transplantation with consideration of urgency based on waiting list survival, instead of being based solely on waiting time. A goal of the policy is to minimize deaths on the waiting list.     

Development of the New Lung Allocation System in the United States

This article reviews the development of the new U.S. lung allocation system that took effect in spring 2005. In 1998, the Health Resources and Services Administration of the U.S. Department of Health and Human Services published the Organ Procurement and Transplantation Network (OPTN) Final Rule. Under the rule, which became effective in 2000, the OPTN had to demonstrate that existing allocation policies met certain conditions or change the policies to meet a range of criteria, including broader geographic sharing of organs, reducing the use of waiting time as an allocation criterion and creating equitable organ allocation systems using objective medical criteria and medical urgency to allocate donor organs for transplant. This mandate resulted in reviews of all organ allocation policies, and led to the creation of the Lung Allocation Subcommittee of the OPTN Thoracic Organ Transplantation Committee. This paper reviews the deliberations of the Subcommittee in identifying priorities for a new lung allocation system, the analyses undertaken by the OPTN and the Scientific Registry for Transplant Recipients and the evolution of a new lung allocation system that ranks candidates for lungs based on a Lung Allocation Score, incorporating waiting list and posttransplant survival probabilities.     

Deceased donor kidney and liver transplantation to nonresident aliens in the United States

BACKGROUND: Policies governing the allocation of deceased donor organs to nonresident aliens (NRAs) have existed from the early days of transplantation. However, there is a paucity of research describing this population. The aim of the present study is to examine characteristics and allocation patterns for NRAs compared to U.S. citizens in the context of the two most common forms of solid organ transplantation. METHODS: The study included kidney and liver transplant candidates and deceased donor transplant recipients from 1988-2005 in the United States. We describe demographic characteristics, insurance coverage, geographic variability, and donor relationship based on citizenship and residency status. We additionally examined the association of citizenship with time to transplantation utilizing survival models. RESULTS: From 1988-2005, there were 2724 solitary kidney and 2072 liver NRA candidate listings with United Network for Organ Sharing. NRA recipients had more self-pay (liver 36% and kidney 22%) and foreign sources (liver 26% and kidney 13%) of insurance coverage. Transplants to NRAs were more frequent than deceased donations deriving from NRAs for both organs. Adjusted models indicated that NRA kidney candidates received transplants at the same rate as U.S. citizens while liver NRA candidates received transplants more rapidly during the pre-Model for End-Stage Liver Disease (MELD; adjusted hazard ratio [AHR] 1.2, confidence interval [CI] 1.2-1.3) and post-MELD (AHR 1.5, CI 1.3-1.7) eras. CONCLUSIONS: NRAs are demographically and socioeconomically diverse and have historically had a more rapid progression on the waiting list to receive a liver transplant. Further discussion and investigation concerning the ethical, economic, and public health ramifications of transplantation to NRA patients are warranted.     

Frequency of whole‐organ in lieu of split‐liver transplantation over the last decade: Children experienced increased wait time and death

Organ shortage is a barrier to liver transplantation (LT). Split LT (SLT) increases organ utilization, saving 2 recipients. A simulation of Organ Procurement and Transplantation Network/United Network for Organ Sharing data (2007‐2017) was performed to identify whole‐organ LT grafts (WLT) that met the criteria for being splittable to 2 recipients. Waitlist consequences presented. Deceased donor (DD) livers transplanted as whole organs were evaluated for suitability to split. Of these DD organs, we identified the adolescent and adult recipients of WLT who were suitable for SLT. Pediatric candidates suitable to share the SLT were ascertained from DD match‐run lists, and 1342 splittable DD organs were identified; 438 WLT recipients met the criteria for accepting a SLT. Review of the 438 DD match‐run lists identified 420 children next on the list suitable for SLT. Three hundred thirty‐three children (79%) underwent LT, but had longer wait‐times compared to 591 actual pediatric SLT recipients (median 147 days vs 44 days, P  < 0.001). Thirty‐three of 420 children died on waitlist after a mean 206 days (standard deviation 317). Sharing organs suitable for splitting increases the number of LT, saving more lives. With careful patient selection, SLT will not be a disadvantage to the adult recipients. With a children‐first allocation scheme, SLT will naturally increase the number of allografts because adult organs are too large for small children.     

Kidney and Pancreas Transplantation in the United States, 1997–2006: The HRSA Breakthrough Collaboratives and the 58 DSA Challenge

Growth in the number of active patients on the kidney transplant waiting list has slowed. Projections based on the most recent 5-year data suggest the total waiting list will grow at a rate of 4138 registrations per year, whereas the active waiting list will increase at less than one-sixth that rate, or 663 registrations per year. The last 5 years have seen a small trend toward improved unadjusted allograft survival for living and deceased donor kidneys. Since 2004 the overall number of pancreas transplants has declined. Among pancreas recipients, those with simultaneous kidney-pancreas transplants experienced the highest pancreas graft survival rates.
In response to the ongoing shortage of deceased donor organs, the US Health Resources and Services Administration launched the Organ Donation Breakthrough Collaborative in September 2003 and the Organ Transplantation Breakthrough Collaborative (OTBC) in October 2005. The 58 DSA Challenge is prominent among the goals adopted by the OTBC. Its premise: were each of the 58 existing donation service areas to increase the number of kidney transplants performed within their boundaries by 10 per month, an additional 7000 transplants over current annual levels would result. Such an increase could potentially eliminate the national kidney transplantation waiting list by 2030.     

National landscape of HIV+ to HIV+ kidney and liver transplantation in the United States

The HIV Organ Policy Equity (HOPE) Act, enacted on November 21, 2013, enables research on the transplantation of organs from donors infected with human immunodeficiency virus (HIV) (HIV+) into HIV+ individuals who, prior to transplantation, are infected with HIV. In 2015, the Organ Procurement and Transplantation Network revised organ allocation policies on November 21, and on November 23, the Secretary of Health and Human Services published research criteria and revised the Final Rule accordingly. The HOPE Act appears to be underutilized to date. As of December 31, 2018, there were 56 donors recovered (50 donors transplanted) resulting in 102 organs transplanted (31 liver, 71 kidney). As of December 31, 2018, 212 registrations were indicated on the waiting list as willing to accept an HIV+ kidney or liver, most of which were waiting in active status. Due to the limited number of transplants performed to date, definitive safety conclusions cannot be reached at this time, though current data suggest that 1‐year patient and graft survival does not deviate in a major way from that observed in HIV+ recipients of non‐HIV+ organs or non‐HIV+ recipients. As safety data are reviewed and disseminated, it is anticipated that HOPE participation will increase should safety signals remain low.     

Waiting in line: should selected patients ever be moved up?

Assuring equitable access of patients to needed organ transplants is a responsibility that must be shared by transplantation teams, the patients, their families, referring physicians, and society as a whole. Barriers of major proportion still exist that strongly bias the initial selection of patients for placement on waiting lists and adversely affect the rates of transplantation among the older age groups, nonwhites, and the poor. The very issue of making up the waiting list is fundamental to the development of fair and equitable distribution of the national resource of organs for transplantation. Actual organ allocation must involve medical judgment and must strive to achieve the maximal benefit to patients. Despite dangers of paternalism and bias masquerading as medical criteria, to overlook outcome predictions in selecting the recipient of a scarce resource is to be irresponsible toward the donor and society as well as to the patients on the list. Insofar as benefit and need can both be served, as in the case of liver transplantation for fulminant liver failure or kidney transplantation in a well-matched recipient, these considerations should far outweigh the poor criterion of length of time on the waiting list. In many instances, it will be the most appropriate choice to give the organ to a patient waiting on the list at home rather than to a desperately ill patient who will doubtlessly die without the operation but whose risks of failure are significantly higher. As difficult as these decisions are, especially in life and death situations, a system of organ allocation based on medical judgment, with appropriate safeguards and thorough monitoring, eventually will prove to be the fairest method.     

The trials and tribulations of liver allocation

Allocation policies are necessary to ensure a fair distribution of a scarce resource. The goal of any liver transplant allocation policy is to achieve the best possible outcomes for the waiting list population, irrespective of the indication for transplant, whilst maximizing organ utilization. Organ allocation for liver transplantation has evolved from simple centre-based approaches driven by local issues, to complex, evidence-based algorithm prioritizing according to need. Despite the rapid evolution of allocation policies, there remain a number of challenges and new approaches are required to ensure transparency and equity on the decision-making process and the best possible outcomes for patients on the waiting list. New ways of modelling, together with novel outcome criteria, will be required to enable a dynamic adaptability of the allocation policies to the ever changing demographics of the donor population and the changing landscape of indications for transplantation.