We examined factors associated with expanded criteria donor (ECD) kidney discard. Scientific Registry of Transplant Recipients (SRTR)/Organ Procurement and Transplantation Network (OPTN) data were examined for donor factors using logistic regression to determine the adjusted odds ratio (AOR) of discard of kidneys recovered between October 1999 and June 2005. Logistic and Cox regression models were used to determine associations with delayed graft function (DGF) and graft failure. Of the 12,536 recovered ECD kidneys, 5139 (41%) were discarded. Both the performance of a biopsy (AOR = 1.21, p = 0.02) and the degree of glomerulosclerosis (GS) on biopsy were significantly associated with increased odds of discard. GS was not consistently associated with DGF or graft failure. The discard rate of pumped ECD kidneys was 29.7% versus 43.6% for unpumped (AOR = 0.52, p < 0.0001). Among pumped kidneys, those with resistances of 0.26-0.38 and >0.38 mmHg/mL/min were discarded more than those with resistances of 0.18-0.25 mmHg/mL/min (AOR = 2.5 and 7.9, respectively). Among ECD kidneys, pumped kidneys were less likely to have DGF (AOR = 0.59, p < 0.0001) but not graft failure (RR = 0.9, p = 0.27). Biopsy findings and machine perfusion are important correlates of ECD kidney discard; corresponding associations with graft failure require further study.

CONTEXT:Transplantation using kidneys from deceased donors who meet the expanded criteria donor (ECD) definition (age > or =60 years or 50 to 59 years with at least 2 of the following: history of hypertension, serum creatinine level >1.5 mg/dL [132.6 micromol/L], and cerebrovascular cause of death) is associated with 70% higher risk of graft failure compared with non-ECD transplants. However, if ECD transplants offer improved overall patient survival, inferior graft outcome may represent an acceptable trade-off. OBJECTIVE:To compare mortality after ECD kidney transplantation vs that in a combined standard-therapy group of non-ECD recipients and those still receiving dialysis. DESIGN, SETTING, AND PATIENTS:Retrospective cohort study using data from a US national registry of mortality and graft outcomes among kidney transplant candidates and recipients. The cohort included 109,127 patients receiving dialysis and added to the kidney waiting list between January 1, 1995, and December 31, 2002, and followed up through July 31, 2004. MAIN OUTCOME MEASURE:Long-term (3-year) relative risk of mortality for ECD kidney recipients vs those receiving standard therapy, estimated using time-dependent Cox regression models. RESULTS:By end of follow-up, 7790 ECD kidney transplants were performed. Because of excess ECD recipient mortality in the perioperative period, cumulative survival did not equal that of standard-therapy patients until 3.5 years posttransplantation. Long-term relative mortality risk was 17% lower for ECD recipients (relative risk, 0.83; 95% confidence interval, 0.77-0.90; P<.001). Subgroups with significant ECD survival benefit included patients older than 40 years, both sexes, non-Hispanics, all races, unsensitized patients, and those with diabetes or hypertension. In organ procurement organizations (OPOs) with long median waiting times (>1350 days), ECD recipients had a 27% lower risk of death (relative risk, 0.73; 95% confidence interval, 0.64-0.83; P<.001). In areas with shorter waiting times, only recipients with diabetes demonstrated an ECD survival benefit. CONCLUSIONS:ECD kidney transplants should be offered principally to candidates older than 40 years in OPOs with long waiting times. In OPOs with shorter waiting times, in which non-ECD kidney transplant availability is higher, candidates should be counseled that ECD survival benefit is observed only for patients with diabetes.

Organ transplantation has progressed, in a relatively brief period of medical history, from an experimental to a standard treatment for end-stage organ failure. The replacement of a diseased heart, liver, or kidney with a functional transplant has become the preferred approach to restoring the well-being of a patient. However, while the number of patients who are medically suitable to undergo organ transplantation has markedly risen, the supply of deceased organ donors has remained insufficient to provide for the increasing demand. Thus, organ procurement and transplant professionals have considered other ways of addressing this organ shortage, such as the transplantation of organs from living donors or from deceased donors whose medical characteristics are not ideal. The ideal deceased donor of an organ has been identified as a donor younger than 40 years of age who has no characteristics that may predispose his or her organs to graft failure after transplantation. Currently, ideal deceased liver donors provide approximately one-third of all livers transplanted in the United States. All other deceased liver donors present a continuum of increased risk of graft failure compared with the ideal donor. The expanded criteria donor (ECD) designation is meant to describe a deceased donor with substantially increased risk of graft failure compared with the ideal donor. Medical history of systemic illness such as malignancy Social history of exposure to transmissible infectious disease Predonation course of hemodynamic instability Serological evaluation of viral infection Evidence of less than optimal organ function prior to surgical recovery Adverse intraoperative recovery events Postrecovery biopsy results Age Cause of death The transplantation of liver allografts (an organ or tissue transplanted from one individual to another of the same species, i.e., human to human) from ECDs is increasing, not only in the New York region but also in most regions of the United States. As the waiting list for liver transplants continues to grow (and the availability of livers from ideal donors remains largely unchanged), there is increasing need to use expanded criteria donor livers (ECDLs). Until now, there has been little medical guidance in determining the more suitable ECDL for transplantation or in the development of selection criteria for the most appropriate recipient. Furthermore, guidance to improve the informed consent of potential recipients of these organs is essential. Thus, Commissioner of Health Antonia C. Novello, MD, MPH, Dr. PH, assembled a Workgroup of national experts to address the use of liver allografts from ECDL. Since the outcome of this Workgroup would have implications not only for New York State but also for the nation, the membership was chosen accordingly. It included the President-Elect of the Organ Procurement and Transplantation Network (OPTN)/United Network for Organ Sharing (UNOS), a representative from the Scientific Registry of Transplant Recipients (SRTR), members of the OPTN/UNOS Liver and Intestinal Transplantation Committee, a liver transplant recipient, ethicists, organ procurement organization representatives, transplant physicians from across the nation, representatives from the 5 liver transplant programs in New York State, and a federal government representative. The Department of Health's positive experience with the Committee on Quality Improvement in Living Liver Donation, which produced a seminal report on live adult liver transplantation in 2002, set the precedent for the Department to utilize the same approach in studying this issue. The Workgroup convened in June, August, and October of 2004. This current report represents the completion of the diligent work of the Workgroup and is presented as guidance on the use of ECDL for the liver transplant community. The members of this Workgroup believe that these recommendations will serve as a reference of data and experience for the rest of the country. The Workgroup acknowledges, however, that the recommendations of this report may be revised as advances in ECDL transplantation occur in the future. ECD, expanded criteria donor; ECDL, expanded criteria donor liver; OPTN, Organ Procurement and Transplantation Network; UNOS, United Network for Organ Sharing; SRTR, Scientific Registry of Transplant Recipients; OPO, organ procurement organization; RR, relative risk; DCD, donor after cardiac death; CVA, cerebral vascular accident; COD, cause of death, MELD, model for end-stage liver disease. To identify characteristics of ECDL To determine if there should be a separate allocation system for ECDL To determine what information should be shared with a potential liver transplant recipient to achieve informed consent when an ECDL is offered New York liver transplant patients undergo transplantation of ECDL at a greater frequency than the rest of the country Recipients in New York State are sicker at the time of transplant than those in the rest of the country Despite these circumstances, the outcomes of liver transplantation in New York State are comparable to the rest of the country To determine if the New York centers' perceptions were valid, the Workgroup requested that the SRTR provide a comparative analysis of the use of ECDL in New York vs. the rest of the nation. The SRTR is the federal contractor responsible for the ongoing evaluation of the scientific and clinical status of solid organ transplantation including kidney, heart, liver, lung, and pancreas transplants. The SRTR comparative analysis is discussed later in this report. Permitting a comparative profile of center/regional practices regarding acceptance of ECDL and recipient selection for these grafts Providing physicians with important information to make judgments regarding the risk of graft failure for their specific patient vs. the benefit that may be derived by transplantation Building public trust by providing information regarding the potential for success, complications, and risks associated with the use of these organs Potentially limiting the availability of deceased donor livers, impacting recipients on the waiting list based on an arbitrary standard that could curtail or limit the transplantation of livers based on a clinical matching of donor and recipient characteristics Potentially inhibiting development of future innovative practices Although there has been presentation of data at the national level about the ECDL,1 there is no nationally accepted definition of an ECDL. Consequently, the Workgroup reviewed data on clinical characteristics that may affect graft survival to help identify what characteristics are indicative of an ECDL. The SRTR has used a relative risk (RR) of graft failure of 1.7 or greater as an arbitrary indicator of an ECD kidney.2 For liver transplantation, the RR compares the risk of graft failure (including death) using a liver from any given donor to that of a liver from an ideal donor (i.e., younger than 40 years old and having no donor characteristics significantly associated with graft failure). For example, a liver graft with an RR of 1.7 has a 70% greater chance of failure compared with a liver from an “ideal” donor (RR = 1.0). Thus, if an “ideal” donor liver graft has a 5% failure than this arbitrary definition would identify donor characteristics indicative of a 8.5% absolute chance of graft failure. The workgroup members employed an RR >1.7 to facilitate discussion and data analysis. (Please note: this working definition was agreed to as a means for data analysis only and, as the report will show, was not adopted as a clinically definitive definition of an ECDL). The characteristics identified by the SRTR in their analyses that were associated with a significantly higher risk of liver graft failure include: increased donor age, partial or split livers (a deceased donor liver that is split and used to transplant two recipients), donors after cardiac death (DCD), black race, cerebral vascular accident (CVA) as the cause of death (COD), and COD other than trauma, CVA, or anoxia (Table 1). Although each of these characteristics is associated with significant risk, none individually reach the threshold of RR ≥ 1.7. It is important to emphasize that none of these characteristics alone would result in a donor being classified as an ECD. It is only when any one of these characteristics is paired with at least one other characteristic of Table 1 that the RR may be ≥1.7. Table 2 demonstrates the combinations of donor characteristics that cumulatively result in a graft failure RR ≥ 1.7. For example, a donor age 60 years or older who also has other risk factors has an RR ≥ 1.7. Since there are many potential combinations of donor characteristics, ECDL represents a spectrum of risk. Because the risk in a particular case depends on the values for each of the factors, a specific RR cutoff for what is an acceptable or unacceptable donor would be arbitrary and might disadvantage patients, especially those with a much higher risk of death without a transplant. By replacing the Xs in Table 2 with the actual range of RRs and the one-year graft survival rates for the patients receiving these transplants, the calculated risks and associated predicted graft survival rates for recipients of each category of ECDL can be examined (Tables 3 and 4). According to the data in Table 4, a donor age 50-59 years who was a DCD or partial/split graft carries an RR of 1.96-1.99 (96% to 99% higher risk of graft failure than an ideal donor). The associated mean one-year graft survival with a donor liver of this nature used for a transplant candidate with average characteristics is 86.9%. However, these survival data do not necessarily predict the outcome for a given recipient with “nonaverage” characteristics. Significant steatosis (fat) Serum sodium >170 at the time of procurement Positive hepatitis serology Donor malignancy (cancer) Further data collection and research will be necessary to determine whether these characteristics impact the ECD matrix. When compared with the rest of the nation, did New York State centers transplant a higher or lower percentage of ECDL (predicted RR ≥ 1.7)? Answer: Yes, New York State centers transplanted a higher percentage of ECDL (24.7%) compared with the rest of the nation (13.4%) (Table 5). What was the percentage of “ideal” deceased donor liver transplants in New York State? Answer: The percentage of “ideal” liver transplants in New York State was 21.8% of all livers transplanted, which was less than the rest of the nation at 35.0% (Table 5). What was the mean RR of deceased donor liver transplants in New York State? Answer: The mean RR of ECD deceased donor liver transplants performed at New York centers ranged from 1.88 to 1.91 (Table 6). The mean RR of non-ECD deceased donor liver transplants performed in New York centers ranged from 1.26 to 1.35 (Table 6). What was the overall retransplant rate by ECD/non-ECD for New York State liver transplant recipients compared with the rest of the country? Answer: Figure 1 shows the percentage of retransplants for both ECD and non-ECD in New York State compared with the rest of the country. New York State centers had a higher rate of retransplantation during the time period cited than the rest of the country for both types of grafts. Recipients in New York State, as well as those in the rest of the country, that received ECD liver allografts had twice the rate of retransplantation as those who received a non-ECD. What were the retransplant rates by ECD/non-ECD for New York State (Region 9) and the rest of the country by OPTN region? Answer: There are 11 OPTN/UNOS organ-sharing regions. The percent of liver retransplantation for ECDL recipients in Region 9 exceeded every other OPTN region except Region 3 (Fig. 2). Percentage of retransplantations (Region 9-New York vs. rest of the country). Source: SRTR-January 1, 1998 to December 31, 2002. Percentage of retransplantations (ECD, non-ECD, overall). Figure 3 represents the number of liver allografts derived from donors outside of New York State compared with liver allografts transplanted in other regions, which were derived from donors outside their respective regions. New York State used a higher percentage of both non-ECD and ECD originating from outside their local region than the rest of the country. Distribution of donor origin for ECD and non-ECD transplants. Source: SRTR-January 1, 1998 to December 31, 2002. New York State recipients of ECDL and non-ECDL had a similar distribution by age, gender, race, and diagnosis as the rest of the country (as indicated by SRTR data not included in this report) Deceased donor livers transplanted in New York State were older than those in the rest of the country (as indicated by SRTR data not included in this report) In New York State and the rest of the country, those who received an ECDL had nearly twice the rate of retransplantation compared with those who received a non-EDCL (Table 5) New York State had a higher retransplant rate than the rest of the country (Fig. 1) Liver allographs were transplanted in New York State into a higher proportion of hospitalized and ICU-bound patients than in the rest of the country. Thirty-five percent of recipients in New York State were in the ICU at the time of transplant compared with 21% for the rest of the country. Twenty-six percent of recipients in New York State were hospitalized at the time of transplant compared with 13% for the rest of the country The study collected information regarding patients hospitalized in the ICU between 1998 and 2002 to determine their severity of illness. Since then, a standard of medical urgency (severity of illness) has been developed nationally by determining a MELD score, so that an objective and consistent determination of illness could be provided for each patient. MELD is a numerical scale, ranging from 6 (less ill) to 40 (gravely ill), that is used for adult liver transplant candidates. It gives each candidate a score (number) based on three laboratory values, and the score is predictive of the risk of death in the absence of a liver transplant within the next three months. A MELD score is calculated using a relatively simple formula that relies on three readily available objective variables: serum creatinine, total bilirubin, and international normalized ratio (INR). What were the liver allograft survival outcomes for recipients in New York State compared with the rest of the country? Answer: Table 7 shows the graft survival for patients undergoing liver transplantation in New York State compared with the rest of the country. What were the patient survival outcomes for recipients in New York State compared with the rest of the country? Answer: Table 8 shows the survival rates for patients undergoing liver transplantation in New York State compared with the rest of the country. Liver transplants from ECDLs are not unacceptable but carry a higher risk of graft failure compared with liver transplants from “ideal” donors. In absolute terms, if an “ideal” donor liver carries a 5% risk of graft failure, then a liver procured from a donor with characteristics defining an RR of graft failure = 2.0 would have a 10% risk of graft failure The use of RR of graft failure as the criterion for defining ECDL is arbitrary and not an absolute predictor of recipient outcome The precise RR of a particular donor should be determined to make a medical judgment on the donor suitability for a given recipient (while considering his/her simultaneous medical urgency). Judgment necessitates a continual reassessment of the recipient's medical condition at the time of a donor offer with the simultaneous quality assessment of the donor organ being offered. Not accepting a donor liver from an ECD may result in the death of a medically urgent patient because another donor liver may not become available in the immediate future Donor age Partial/split liver DCD liver Donor COD other (COD not from trauma, CVA, or anoxia) Donor COD CVA Donor race/black Other characteristics, such as steatosis (fat), serum sodium >170, positive hepatitis serology, and donor malignancy were discussed by the Workgroup as characteristics potentially indicating a higher rate of graft failure. The Workgroup concluded that the data analyses included in this report will be helpful to practitioners deciding which ECDL are appropriate for transplantation. The decision to transplant an ECDL should be determined by the recipient's medical condition at the moment of an organ offer vs. the risk of waiting for the next organ offer from another future donor of unknown quality Since the waiting list is not a static entity and the characteristics of donors are not the same from offer to offer, allocation policy should not restrict the availability of organs to individual candidates and should not supersede clinical judgment in assessing risks and alternatives for individual candidates The third issue the Workgroup considered was the information that should be shared with a potential liver transplant recipient to achieve informed consent. A discussion of the transplant alternatives, including the transplantation of an ECDL, should be included early in the informed consent process so that the recipient has time to consider the information in a nonurgent context. Obviously, this would be difficult to do if a candidate's first presentation is at a time of medical urgency. Nonurgent candidates should otherwise retain informational materials to which they can refer when making an informed decision at the time of a donor offer. The inclusion of family members, spouses, and/or a significant other in the informed choice discussion should be encouraged because they may be called upon to give consent if the recipient's medical condition renders him/her unable to consent. Potential recipients should be permitted to change consideration of receiving an ECDL at any time during the process. The Workgroup recommends the following stages of consent be used for all liver transplant candidates. The quality of the deceased donor pool The characteristics of an ECDL The possibility of live donor transplantation for appropriate candidates at centers that perform this procedure The use of donors with varying degrees of risk of failure when compared with the ideal donor The risks/benefits/alternatives of using such a donor vs. waiting for the next donor in the context of the waiting candidates' severity of disease and mortality risk The MELD score outlined earlier can be helpful to define the risk of death on the list and the risk of waiting in comparison to the benefit of the transplant (with or without a graft from a donor with an increased RR). The transplant physician and/or transplant coordinator should provide ongoing education to the recipient while he/she awaits transplantation. As the candidate's medical condition evolves, the ECDL option should be readdressed at appropriate intervals. At the time of the proposed transplantation, final consent should be obtained as the physicians have a more precise assessment of the risks associated with undergoing an ECDL transplant vs. the risk of waiting for the next available donor. The New York State Department of Health Workgroup includes the following members: Francis L. Delmonico, MD (Chair), Professor of Surgery, Harvard Medical School and Massachusetts General Hospital, Medical Director, New England Organ Bank, Boston, MA, President Elect, United Network For Organ Sharing, Arthur Aufses, Jr., MD, Department of Health Policy, Mount Sinai Medical Center, New York, NY; Adel Bozorgzadeh, MD, Associate Professor of Surgery, Director of Solid Organ Transplantation, University of Rochester Medical Center, Rochester, NY; Debbie Delgado-Vega, President and CEO, Latino Organization for Liver Awareness, Bronx, NY; Dale A. Distant, MD, Associate Professor, Director, Transplantation Service, SUNY Downstate Medical Center, Brooklyn, NY; Nancy Neveloff Dubler, LLB, Director, Division of Bioethics, Albert Einstein College of Medicine, Professor of Bioethics, Department of Epidemiology and Social Medicine, Montefiore Medical Center, Bronx, NY; Sukru Emre, MD, Professor of Surgery and Pediatrics, Director, Adult and Pediatric Liver Transplant Programs, Mount Sinai Hospital, New York, NY; Sandy Feng, MD, PhD, Assistant Professor of Surgery, Department of Surgery, University of California, San Francisco, CA; Richard B. Freeman, Jr., MD, Professor of Surgery, Tufts University School of Medicine, New England Medical Center, Division of Transplant Surgery, Boston, MA; John J. Fung, MD, PhD, Chairman, Department of General Surgery, Director, Transplant Center, Cleveland Clinic, Cleveland, OH; Fredric D. Gordon, MD, Medical Director of Liver Transplantation, Lahey Clinic Medical Center, Burlington, MA; Richard D. Hasz, Vice President of Clinical Services, Gift of Life Donor Program, Philadelphia, PA; Milan Kinkhabwala, MD, Surgical Director, Liver Transplantation, New York Presbyterian Hospital, New York, NY; John R. Lake, MD, Professor of Medicine and Surgery, Director of Liver Transplantation Program, University of Minnesota, Minneapolis, MN; Robert M. Merion, MD, Professor of Surgery, Division of Transplantation, University of Michigan Health System, Ann Arbor, MI; Jeffrey Orlowski, Executive Director, Center for Donation and Transplant, Albany, NY; C. Wright Pinson, MD, Professor and Chairman, Department of Surgery, Chief, Division of Hepatobiliary Surgery, and Liver Transplantation, Vanderbilt University Hospital, Nashville, TN; Tia Powell, MD, Executive Director, New York State Task Force on Life and the Law, New York, NY; Patricia Ann Sheiner, MD, Director, Liver Transplantation and Hepatobiliary Surgery, Westchester Medical Center, Valhalla, NY; Lewis Teperman, MD, Director of Transplantation; New York University Medical Center, New York, NY; Carla Williams, Executive Director, New York Center for Liver Transplantation, East Greenbush, NY; and Hui-Hsing Wong, MD, JD, Operations and Analysis Branch, Division of Transplantation, Healthcare Systems Bureau, Health Resources and Services Administration, Rockville, MD. Other members of the Workgroup from the New York State Department of Health include: Antonia C. Novello, MD, MPH, Dr. PH, Commissioner, New York State Department of Health; Wayne Osten, Director, Office of Health Systems Management; Lisa Wickens, RN, Assistant Director, Office of Health Systems Management; Nancy Barhydt, Dr. PH, RN, Director of Clinical Affairs, Office of Health Systems Management; Judy Doesschate, Esq., Associate Attorney, Division of Legal Affairs; Sherry Emrich, RN, Assistant Hospital Program Director/Western Regional Office; Dawn Maynus, Program Research Specialist III, Bureau of Health Care Research, Information Services, Division of Health Care Standards and Surveillance; Lisa McMurdo, RN, MPH, Director, Division of Health Care Standards and Surveillance; and Kimberly Valente, RN, Health Policy Associate, Bureau of Hospital and Primary Care Services, Division of Health Care Standards and Surveillance.