The Allocation of Cadaver Kidneys for Transplantation in the United States
Authors: JOHN F. NEYLAN, MOHAMED H. SAYEGH, THOMAS M. COFFMAN, GABRIEL M. DANOVITCH, ALAN M. KRENSKY, TERRY B. STROM, LAURENCE A. TURKA, WILLIAM E. HARMON
Journal: Journal of the American Society of Nephrology (1999)

The development of organ transplantation as a widely available and clinically effective therapy has provided an enormous benefit for the care of patients with end-stage renal disease (ESRD). One-year cadaver donor graft survival rates have improved from 52% to nearly 90% between 1977 and 1998 (1, 2). Such outcomes have encouraged more patients to request transplantation as their preferred mode of therapy. Unfortunately, the number of cadaver donors has not increased at an equivalent rate to meet the expanded demand. The problem is compounded further by the increasing prevalence of patients treated for ESRD (2) (Figure 1). The widening gap between the number of renal transplant candidates and available donors is shown in Figure 2. As the imbalance between supply and demand worsens, the allocation of donor organs to recipients becomes an increasingly important issue and the subject of increasing controversy. The factors that have influenced the development of organ donation, recovery and allocation, and consequent access to renal transplantation in the United States are complex. The present system is dependent on volunteerism, public trust, and a continued assessment of outcomes to achieve a difficult balance of equity and justice.Figure 1: . Living end-stage renal disease (ESRD) patients on December 31 by year and treatment modality. ▪, number of dialysis patients; [UNK], number of patients with functioning transplants. Adapted from reference (2).Figure 2: . Number of candidates for cadaver kidney transplants ([UNK]) and the number of cadaver kidney donors (▪) in the United States from 1988 to 1998. Each donor may contribute two kidneys, so the number of transplants is greater than the number of donors. Adapted from references (3) and (4).This report summarizes the history and development of cadaver kidney allocation in the United States and is meant to serve as a background overview. The American Society of Nephrology (ASN), as a professional organization whose members are responsible for patients who are dependent on the fair allocation of cadaver kidneys for transplantation, must develop a position on this difficult issue. The ASN Transplant Advisory Group has initiated the process with this overview and proposes that the ASN develop an official position on kidney organ allocation by the year 2000. Donor Shortage At the end of 1988, there were 13,943 people waiting for cadaver kidney transplants in the United States. In that year, 7,061 cadaver and 1,812 living donor transplants were performed (3). Currently, there are 41,744 patients enrolled on the cadaver waiting list (a 200% increase), while only 8,938 cadaver donor renal transplants (a 24% increase) were performed in the United States last year (4) (Figure 3). The average waiting time for cadaver donor renal transplants has increased to more than 1000 days, with some groups, such as African-Americans, waiting substantially longer. If the waiting list increases by 20% per year and the number of cadaveric kidney transplants remains below 10,000 per year, it is anticipated that by 2010 the mean waiting time for a transplant will approach 10 years, unless there are dramatic advances in xenotransplantation or tissue engineering.Figure 3: . Number of cadaver donor (▪) and living donor ([UNK]) renal transplants performed in the United States from 1988 to 1998. Adapted from references (3) and (4).Partly as the result of this lengthening waiting period, the use of living donors, especially living unrelated donors, has increased dramatically. Living-donor kidney transplants accounted for 31% of all transplants in 1998 (4), and the number of "emotionally related" donations has increased sevenfold in the past decade (3). In addition, expanded criteria of medical acceptability of cadaveric donors have been utilized with greater frequency; and newer experiments, such as proposals for donor exchanges between blood type mismatched but otherwise suitable living donor-recipient pairs (5), age matching for elderly recipients (6,7,8), and paired kidney transplants (9, 10) have all occurred because of the increasing discrepancy between the number of donors and candidates for kidney transplantation. Structure and History of Kidney Allocation Organ Procurement Organizations Organ Procurement Organizations (OPOs) developed in the 1960s as a result of the increasing success in the transplantation of cadaveric kidneys. In the early days, these organizations resulted from the voluntary collaborative efforts of multiple transplant programs in a localized geographic area. After the passage of federal law creating the Medicare entitlement program for patients with ESRD in 1972, the proliferation of kidney transplantation as a federally funded therapy for ESRD and the consequent demand for more donor organs stimulated a dramatic increase in the number of OPOs nationwide. In the latter half of the 1970s, Medicare funding became available for independent as well as hospital-based OPOs, leading to further refinements of these operations. Today, there are 65 active OPOs servicing defined regions throughout the United States. There is, however, no universally accepted structure for an OPO. For example, some OPOs service a small geographic area and a single transplant center, whereas other OPOs serve as many as six states or more than 15 transplant centers. In some areas of the country, there are multiple OPOs within one state or even one city, whereas in others a single OPO serves many states. Beginning January 1, 1996, the Health Care Financing Administration required that an OPO include an entire state or territory, or that it recover organs from at least 50 potential or 24 actual donors per calendar year (11). There appears to be variable performance of OPOs across the country when assessed according to the traditional, although increasingly contested, productivity measure of organs procured per million base population. Based on the 5,788 cadaveric donors from whom organs were recovered in 1998 and an estimate of the U.S. census at 272.6 million population, the national average is 21.2 donors per million population per year. The wide range for individual OPOs varies from approximately 10 to 40 donors per million. Some of the difference may be related to substantial regional differences in medically suitable organ donor candidates, differences in automobile fatality rates, and the incidence of homicide and other traumatic causes of death. Also, there appear to be cultural differences in attitudes toward donation as well as differences in permission rates between rural and urban areas. Thus, newer performance measures based instead on numbers of medically suitable candidates are being proposed to more accurately define OPO productivity. Nonetheless, it is clear that some OPOs have taken a leadership role in developing more innovative educational programs and in the implementation of new protocols, such as recovery of organs from non-heart-beating donors (12,13,14). Comprehensive death audits of hospital records have yielded considerably higher estimates of medically suitable donors than the current national average, perhaps as high as 55 donors per million (15). Thus, actual conversion rates of suitable donors may be less than 50% of the maximal potential. In 1998, in an effort to enhance potential donor identification and conversion to actual organ recovery, the Department of Health and Human Services (DHHS) issued a rule for conditions of hospital participation in Medicare that required hospitals to notify OPOs of all potential deaths. This rule was based on an experiment in Pennsylvania that demonstrated enhanced donor identification and conversion when experienced OPO staff were able to contact donor families and direct the request for donation (16, 17). Some have suggested that the 5.6% increase in cadaver donors for 1998 may be in part attributable to the implementation of this new rule nationwide. However, even with such measures in place, family refusals remain the most significant barrier to donation, turning down, on average, more than one out of every two requests for organ donation (18, 19). Public attitudes and behavior thus remain a significant hurdle. National Organ Transplant Act In 1984, Congress passed PL 98-507, known as the National Organ Transplant Act (NOTA), which prohibited the sale of human organs, established grants for OPOs, and called for the establishment of a national system of organ sharing. In addition, NOTA created a multidisciplinary task force to conduct an examination of organ donation and transplantation. The task force's extensive list of recommendations included the setting of performance standards for OPOs and transplant centers, as well as the establishment of protocols within hospitals dealing with brain death and organ donation (20). One important outgrowth has been the Uniform Anatomical Gift Act, now established in every state, which maintains the right of every individual aged 18 years or older to donate organs or tissues for purposes including transplantation. The legislation further establishes the right of the individual to designate such direction before death and validates the legality of such methods of declaration as the organ donor card. These declarations are also legally binding even when an attempted contravention by next of kin creates conflict. Organ Procurement and Transplantation Network The Omnibus Budget Reconciliation Act of 1986 (PL 99-509) established that all OPOs and transplant centers become part of a nationwide Organ Procurement and Transplantation Network (OPTN). The OPTN was charged with developing policy for allocation of cadaver source organs for transplantation. In addition, Congress authorized the creation of a scientific registry to track outcomes for all organ transplants performed in the United States. The contracts for both functions can be awarded individually, but the United Network for Organ Sharing (UNOS) successfully bid for that contract and has remained the provider to this day. UNOS had been established in 1977 as an outgrowth of the Southeastern Organ Procurement Foundation (SEOPF), a confederation of transplant programs sharing organs regionally via a computerized matching program. UNOS extended this concept to a national level as a means to optimize matching strategies and improve the efficiency of organ sharing. As the operation grew, UNOS created The Kidney Center in 1982, renamed the Organ Center in 1984, to reflect its expanded operations in other transplantable organs. This 24-hour operation coordinated the allocation of available organs to the candidates listed in the computer records. With the award of the national OPTN contract, UNOS changed its structure to that of a nonprofit, private voluntary organization made up of transplant professionals and public members. UNOS is governed by a Board of Directors, which is currently composed of 40 individuals who represent diverse constituencies. All organ transplant programs are grouped into 11 geographic regions (Figure 4), and a councilor from each of those regions sits on the Board of Directors. The Board is composed also of representatives of patient groups, donor families, histocompatibility laboratories, OPOs, and professional societies. Although all transplant programs belong to UNOS, their compliance with UNOS policies remains voluntary. UNOS does not have any statutory authority to enforce its rules until the Secretary of DHHS approves such policies and by-laws, which has not yet happened. UNOS has established a Scientific Registry to track data relating to organs procured and their functional outcomes in transplant recipients (3). Organ-specific registries were created for each transplanted organ and were maintained by subcontractors. In the case of kidney transplantation, the database is maintained at the University of California at Los Angeles.Figure 4: . Map of United Network for Organ Sharing regions. From reference (3).Organ Allocation Policies Organ allocation policies have developed in a consensus manner in an attempt to balance the competing principles of medical utility and fairness. The OPTN contractor and its committee structure have attempted to find appropriate factors to rank potential recipients of scarce transplantable organs based on their likelihood of receiving an organ and their likely outcomes after transplantation. For instance, the demonstration of superior long-term graft survival with 6-antigen matched (or 0-antigen mismatched) kidneys has led to the mandated sharing of such organs on a national basis. Historically, these best-matched transplants made up approximately 5% of the total cadaver renal transplants, but this percentage has been growing and is currently 13.8% as the number of candidates and the amount of time they wait is increasing. In the absence of such a match, the donor organ is allocated locally to ABO blood group-compatible candidates prioritized on the basis of a computer algorithm that assigns points based on length of time waiting, present state of alloimmunization, and the quality of HLA matching. Children are given preference and are awarded additional points based on their age at the time of listing. All potential recipients with the same donor ABO blood type are ranked according to these parameters (Table 1), and the individual ranked highest is the preferred potential recipient. Factors such as unavailability, intercurrent illness, or a positive final crossmatch may come into play and lead to the designation of alternate candidates. In some OPOs, special consideration is given to diabetic candidates for combined kidney-pancreas transplantation, and one of the donor kidneys is allocated with a recovered pancreas.Table 1: UNOS point system for cadaver kidney allocationaWhen a donor becomes available in a particular OPO, this matching process is applied to the group of recipients listed by the transplant hospitals within that OPO. As noted above, the size of OPOs and the number of potential recipients listed within that OPO vary widely. If no suitable candidate exists within the OPO, the allocation is expanded to the region and subsequently to the entire national list, if necessary, although practical time and logistical constraints must be weighed as increasing cold ischemia time beyond 24 to 48 hours may lead to poorer outcome (21,22,23). Although this single system is supposed to apply to the allocation of all cadaver kidneys, exceptions and designated experimental allocation systems do exist (24). The exceptions are generally categorized as Alternative Local Units (ALUs), variances, and sharing agreements. ALUs constitute subsections of OPOs, entire states, UNOS regions, or other geographic areas that serve as the basis of local organ distribution rather than the recovering OPO. Variances are alternative point systems that generally emphasize different components of the matching system, some giving greater weight to time on the waiting list, panel-reactive antibody, or other matching strategies. Sharing agreements occur between OPOs within or between a given UNOS region. All exceptions require ratification by the Board of Directors of UNOS and are periodically reviewed to ensure that they are maximizing the efficient use of donor organs and that the allocation scheme is primarily patient-driven rather than transplant center-driven. Allocation of kidneys according to the standard UNOS point system provides no priority based on the medical condition of the recipients who are all presumed to have access to chronic dialysis. Difficult decisions regarding the relative disability, morbidity, and potential for rehabilitation of kidney transplant candidates are therefore avoided. In this respect, kidney allocation differs substantially from that for recipients of heart and liver transplants whose organs are distributed based on their medical "status." However, there are some dialysis patients who are indeed in "urgent need," most typically because of dialysis access failure or progressive neuropathy. Some OPOs have developed variances that deal with this issue, although the majority have not. In 1991, UNOS undertook a feasibility study of a single nationwide list for the sharing of cadaver kidneys (25). The study considered the proposal as a means to reduce the perceived inequities associated with the wide regional variations in waiting times. The study concluded that a national single list would create prolonged ischemic times for kidneys transported across broad geographic distances. The consequent preservation injuries would, in turn, have a negative impact on patient and graft survivals. In addition, the increased transport and laboratory costs of such a system, given present technologies, was deemed to be prohibitive. Multiple Organ Transplants Renal failure is a common feature of end-stage hepatic (ESLD) and cardiac disease, and as the numbers of liver and heart transplants have increased so have the requirements for kidney transplants in combination (26, 27). In 1997 the UNOS database reported 145 kidney transplants performed in combination with other nonpancreatic organs and the numbers are increasing. The kidney/liver combination (KLTx) accounted for approximately 85% of these transplants (26). There has been controversy, however, regarding the necessity for KLTx in patients with ESLD and potentially reversible renal dysfunction, often loosely designated as hepatorenal syndrome (HRS). Between 1988 and 1995, the renal diagnosis for 11.6% of all KLTx was reported to be HRS, but for a further 33% the diagnosis was described as "other" or "unknown," and many of these cases likely had potentially reversible causes of renal failure. The overall mortality after liver transplantation for patients with a serum creatinine level >2 mg/dl is not improved by KLTx as opposed to liver transplant alone (26), although clearly there are some patients who develop irreversible renal failure perioperatively and would benefit from KLTx. Preoperative renal dysfunction alone, or even the need for preoperative hemodialysis, should not in itself be regarded as an indication for KLTx. Further work is required to help determine the clinical features of those patients with ESLD whose renal failure is unlikely to improve after liver transplantation and would therefore be appropriate candidates for KLTx. Current Controversy Since its inception, the OPTN has lacked the authority to enforce its policies since they have not been endorsed and published by the executive branch of the federal government. All U.S. transplant programs and OPOs have complied with the OPTN's policies voluntarily. However, increasing concerns about potential violations and disparities in allocation of what has been termed a "scarce national resource" focused attention on the relationship of the federal government to the privatesector OPTN. In 1998, the Secretary of DHHS submitted a proposed final rule that would provide this authority (28). This rule contained principles for allocation to promote wider sharing of organs and to reduce significant geographical differences in waiting times. UNOS and some other transplant organizations have objected to these proposed rules, stating that the Secretary may be attempting to set medical policy, which should be the purview of the medical community. When UNOS and DHHS could not reach agreement on the proposed rule, Congress held public hearings in August 1998 to examine the controversies (29). Several issues were outlined in the ensuing debate. One of those issues is allocation of organs to the sickest patients first. This principle pertains principally to organs for which there is currently no satisfactory alternative life-sustaining treatments. Such is the case for liver and heart transplants. Some argue that if organs are allocated to the sickest first, smaller transplant programs with fewer very sick patients on their waiting lists would receive fewer donor organs than they currently do and might be forced to close. Furthermore, if small, particularly specialized or isolated programs closed, access to transplantation might be diminished for some candidates. At its most recent Board of Directors meeting in June 1999, UNOS approved a revision of liver allocation that requires that cadaver livers be offered first to status 1 patients (the sickest liver transplant candidates) within the region first, before they are distributed within the recovering OPO. This revision does not apply to heart or kidney allocation. Another controversial issue concerns the influence of local transplant programs to donation efforts and actual recovery in their local areas. Some claim that donation would suffer if local programs were to have diminished access to locally recovered organs or if transplant programs were to close. Public opinion surveys on the subject of local use of organs have not clearly demonstrated a preference on this issue. Based on the continuing controversy and lack of clear consensus, Congress subsequently passed legislation as part of an appropriations bill that delayed implementation of the proposed rule for 1 year, until the fall of 1999. That legislation also mandated the Institute of Medicine (IOM) to study the issue of organ allocation and produce a report by the summer of 1999. The IOM expert panel has been constituted and is expected to meet this timetable. In the meantime, a number of states have reacted to the allocation controversies by placing embargoes on cadaver organs recovered within their state borders to restrict their use to transplant programs within their borders. Commentary Organ recovery has improved only modestly in recent years while the demand continues to increase. Despite short-term improvements, long-term renal cadaveric allograft survival remains finite with a current half-life of 10 to 11 years (30). Much of the increase in cadaveric organ donation has come through the expanded use of older donor organs (approximately one-quarter are from donors over the age of 50 years) and other organs with preexisting parenchymal disease such as hypertension and diabetes. The overall discard rate for cadaveric organ recovery has increased to 12%, largely due to the expanded criteria of potential medical suitability. Outcomes for recipients of organs from such expanded donors are negatively influenced with increased requirement for acute dialytic support, decreased renal function and graft survival, and increased patient mortality (21,22,23). Combined organ transplantation such as simultaneous kidney-pancreas for selected type I diabetic patients, or kidney-liver or kidney-heart transplants is also presenting a growing ethical dilemma for the allocation of kidneys alone as these combined transplants reduce access and increase waiting times for ESRD-only patients. The median waiting time for patients awaiting a kidney alone is approximately three times longer than for patients listed for a combined kidney-pancreas transplant in some OPOs. Changes in the distribution algorithm for liver transplants that favor the sickest ESLD patients are also likely to increase the pressure for KLTx and therefore remove kidneys from distribution to the kidney waiting list. Also, as the waiting time for kidney transplants inexorably lengthens, the demand for kidneys for patients with failing dialysis access and other progressive medical problems that might qualify them for emergency consideration for kidney transplantation increases. The nephrology community will be forced to devise a manifestly equitable way to address these pressing needs without unfairly disadvantaging the majority of stable dialysis patients. Regional variations in cadaveric kidney waiting times are dependent on many factors, including cadaveric organ availability, access to living donor organs, local competition for supply including ESRD prevalence, access to the transplant evaluation process, and the relative frequencies of donor-recipient pool biologic incompatibilities that may affect status on a given match-run. Nonetheless, the existence of these variations, whether they are real or apparent, suggests to some that the allocation of organs for transplantation in the United States is not uniform for all citizens in need. Recently, the local use of cadaveric kidneys has decreased slightly and wider sharing has increased, but the appropriate relationship of local use to wider sharing remains highly controversial both within the transplant community and in political and regulatory bodies. What can be done to address these problems? Obviously, we must continue to reduce organ wastage by improving short- and long-term graft survival rates both through basic science and clinical research efforts. Also, living donor kidney transplantation is at present the least expensive and most successful kind of organ transplant. The growing number of these types of transplants may be one of the most effective means currently available to deal with the increasing demands, but we must be extremely careful to avoid excessive risk for living donors (31). Adults who have donated a kidney for transplantation have been shown to have a life expectancy which actually exceeds that of the general population, which is likely due to the rigorous screening presently in practice which selects only the healthiest candidates (32, 33). Transplant centers must continue to exercise the same diligence, even as they seek to increase the number of these operations. And finally, increased recovery of cadaver organs suitable for transplantation is also critical. Every transplant program must feel a sense of urgency to expand efforts in all three of these areas. In the setting of the profound mismatch between supply and demand, difficult choices must be made. It is paramount that such decisions continue to be made in an open and fair manner, as the system of organ allocation and accessibility to transplantation must always be open to scrutiny and careful analysis. Public trust is critical to the success of organ transplantation in the United States, and every transplant candidate and donor family must be assured that the allocation system is fair. The medical community should work together to ensure public confidence and support. Unfortunately, the failure of the transplant community to reach consensus on organ allocation has permitted the issue to become a divisive political one, which is now being debated by the legislative and executive branches of the federal government. If organ allocation is to become a medical issue once again, the medical community will have to work with renewed energy and collaboration. The Transplant Advisory Committee will meet during the 1999 ASN annual meeting to draft a position paper for ratification by the ASN Council. Members' comments and suggestions are welcome.