A consensus meeting to develop guidelines that would improve the recovery and transplantation of organs from the cadaver donor was held on 28–29 March 2001, in Crystal City, Virginia, sponsored by the American Society of Transplant Surgeons and the American Society of Transplantation. The crisis in organ supply persists and the continuing shortage presents a compelling responsibility for the transplant community to maximize the use of organs procured from cadaver donors.
Nearly 100 participants included physician and surgeon members of the American Society of Transplantation (AST), American Society of Transplant Surgeons (ASTS), medical and executive directors of Organ Procurement Organizations (OPO), representatives from the Department of Health and Human Services (DHHS), the National Kidney Foundation (NKF), the International Society for Heart and Lung Transplantation (ISHLT), the Scientific Registry for Transplant Recipients University Renal Research and Education Association (URREA), and the United Network for Organ Sharing (UNOS).
Five work groups were assembled that focused upon maximizing the use of hearts, lungs, livers, kidneys, and cadaver donors with a history of malignancy or a serology testing positive for hepatitis C or B virus. The report is given by the deliberations of each work group.
The Kidney Work Group
The discard rate of kidneys procured from the cadaver donor in USA has been increasing to an alarming level of more than 15% of those kidneys recovered for transplantation. If the utilization of recovered kidneys over 45 years of age matched the rate of recovery and transplantation accomplished in Spain, it would increase the rate of donors per million in USA by 38%. Approximately 50% of kidneys from cadaveric donors over 60 years of age (older age donors) are not transplanted due to donor quality.
Enhancing the opportunity to transplant kidneys from the older age donor could help decrease the continuing disparity between the number of patients on the transplant waiting list and the number of patients receiving a transplant each year. The disincentives to transplanting older cadaver donor kidneys include their likely dysfunction immediately following transplantation because older donor kidneys have the longest mean preservation time (Figure 1). The relative risk of dialysis after transplantation is 1.5 times greater in recipients of kidneys from donors > 55 years of age vs. < 55 donor. Importantly however, only the 6-antigen-matched kidneys provide a net benefit (in terms of graft survival) to the recipients of kidneys from older donors (Figure 2). This outcome benefit of national sharing is not realized for older donor 0 mm kidneys. Refinement of distribution policies would encourage centers to be receptive to transplanting older donor kidneys by expediting placement to a list of pre-informed candidates who would accept such older donor kidneys.
The Kidney Work Group goals were to increase the utilization of older donor kidneys, improve patient outcomes by decreasing cold-storage times and delayed graft function; and thus, decrease hospital length of stay and costs.
The kidney proposal of the conference participants was to allocate older donor kidneys > 60 years of age to a pre-informed group of patients based upon waiting time only. These recipients would be identified for the marginal donor kidney before organ procurement. UNOS could develop a standard policy whereby a local OPO could adopt the policy upon notification to UNOS of local OPO approval. Finally, allocation would occur at the level of the OPO, except for the identification of a 6-antigen-matched recipient nationally.
There was an additional objective to evaluate the use of biopsies in the decision to transplant a kidney from an older age donor. Currently, biopsies at the time of recovery assume an importance in kidney distribution that is not supported by available evidence correlating the biopsy findings to short- or long-term function following transplantation. Centers and OPOs would be encouraged to obtain wedge biopsies, when clinically indicated, to determine the utility of biopsies for long-term outcome.
The final consideration of the participants was to assess functional data using the Cockcroft-Gault formula. The proposal was to compare the Cockcroft value to biopsy findings determining the utility of either or both in predicting immediate and long-term function of the older age donor kidney. These data could be used to analyze the effect of this program upon the discard rate of kidneys recovered from the older age donor, comparing the 2 years after the OPO adoption of the proposal with the 2-year period immediately prior to its inception.
This Crystal City Kidney proposal was modified subsequently by collaboration with the OPTN (UNOS) KP Committee (J. Wynn), the UNOS Organ Availability Committee (R. Metzger), and URREA (F. Port). The result of their interaction with the Crystal City kidney group was to set forth a definition of the marginal cadaver kidney donor not only by age, but also according to a relative risk of graft failure of > 1.7 for donors > 50 years of age, and at least two of the following factors: creatinine > 1.5 mg/dL, a cerebral vascular accident as a cause of death, and hypertension when compared to a reference group of non-hypertensive donors between the ages of 10–39 whose cause of death was not CVA, and whose creatinine was <1.5 mg/dL (Table 1). The difference in outcome for kidneys recovered from donors with a relative risk of graft failure of > 1.7 is shown in Figure 3.
Table 1. : The expanded kidney donor. The decision matrix using relative risk of graft failure > 1.7 for donors older than 50 years of age, shown below, are now the UNOS approved expanded criteria by which kidney donors are defined as expanded and placed into the expedited system
Donor age categories
CVA = CVA was cause of death.
HTN = history of hypertension.
Creat > 1.5 = creatinine > 1.5 mg/dL.
CVA + HTN + Creat > 1.5
CVA + HTN
CVA + Creat > 1.5
HTN + Creat > 1.5
Creatinine > 1.5
None of the above
The following proposal of the joint working group was subsequently approved by the UNOS Board on 15 November 2001. Kidneys procured from expanded criteria donors will be allocated preferentially to patients determined to be suitable candidates: first, for zero-antigen-mismatched patients among this group of patients with time limitations; and next, for all other eligible patients, locally, regionally, and nationally, based upon time waiting and not HLA matching. The UNOS Organ Center will attempt to place expanded criteria donor organs for the for zero-antigen-mismatched patients, according to the national list of patients waiting for expanded donor kidneys for a period of 2 h, after which time the UNOS Organ Center will notify the Host OPO that it may allocate the expanded criteria kidneys by the standard geographical sequence of local and regional allocation. OPOs would be required to identify potential recipients (i.e. perform a match run and start the process for notifying the appropriate transplant program(s) regarding the organ offer) for kidneys they procure from expanded criteria donors within 6 h post cross-clamp or offer the organs for eligible patients listed regionally and then nationally.
The Liver Work Group
There is an ethical imperative to address the ever-increasing list of patients waiting for a liver allograft; at the same time, there has been an under-utilization of existing technology and an inefficient use of current liver donor potential. The Liver Work Group identified multiple issues that could be considered for review: expand the use of non-heart-beating donors; broader use of marginal organs; more efficient placement of cadaveric organs; maximization of pre- and post-transplant survival; wider application of innovative technologies; and maximizing the use of split livers. Justification for a more aggressive use of expanded donors of all types is readily provided by the growing disparity between the donor and recipient pools for all organs. Faced with these and other complex study topics, the Liver Work Group chose to address split liver transplantation. While the incremental benefit may be limited in terms of the number of livers regained, the structural paradigm provided by the development of a policy to enhance the use of split livers would be useful in other areas for the expansion of allograft use.
It is estimated that 20% of the approximately 6000 cadaveric donor livers could be split for two recipients. Wasted grafts occur both in left lobe reductions and non-use of left lobe segments from adult donors. The explosion of recent use of living donors for both adults and children has driven further evolution of split technology, suggesting that SLT and LRT will ultimately be complementary therapies. The results of adult/infant split are equivalent to whole organ grafting.
The Liver Work Group concluded that splitting cadaveric livers for transplantation of two adults, while promising, was still experimental technology. For this reason, the Liver Work Group also concluded that the development of a national policy for splitting a single cadaveric liver for two adult recipients is premature. On the other hand, experience with splitting one cadaveric liver into a left lateral segment graft (LLSG) for a pediatric recipient and a right trisegment graft (RTSG) for an adult recipient was sufficient to conclude that this should be the standard of care for donors meeting the appropriate criteria for the split procedure (see Table 2). The Liver Work Group recognized the necessity of promoting this conclusion because there are still many liver transplant procedures performed for children where the cadaver liver graft is ‘reduced’ in size to obtain a graft small enough for the pediatric recipient, but the remaining liver segments are discarded without regard for utilizing this remaining segment. Furthermore, the Liver Work Group recognized that both patient and graft survival for LLSGs transplanted into pediatric recipients are comparable to whole organ transplantation, and patient and graft survival for RTSGs transplanted into adults are equivalent to whole organ adult transplantation (see Figures 4 and 5). Estimates of potential cadaveric grafts meeting criteria for split transplants suggest that if the 20% of donor livers suitable for split were realized, this would increase the total number of liver allograft recipients by 1000 per year. For these reasons, the Liver Work Group felt one important method for maximizing the use of cadaveric organs would be to recommend a national policy for splitting of appropriate donors into LLSG and RTSG whenever possible (see Figure 6), treating the cadaveric liver meeting split criteria (see Table 2) as a paired organ. The simultaneous double allocation would follow current policy, and patient and geographic sequences would remain intact.
Table 2. : Proposed Crystal City Criteria for split liver donation
• Age > 10 and < 45
• Hemodynamically stable (see recommendations from the Heart Work Group)
• ICU < 5 days
• LFT's < 5X, serum sodium < 170, Steatosis < 20%
The two accepting centers will need to communicate surgical responsibilities and any anatomical consideration with one another prior to the donor procedure. Teams with significant experience with the split technique should be encouraged to perform the in situ split and teach less experienced teams at the outset.
Split liver procedures will be monitored via UNOS reporting and all procedures will be entered into the ASTS split liver database which would be maintained by Jean Emond and Robert Merion and the ASTS informatics group. This will entail OPO reporting split procedures to UNOS and identifying centers receiving LLSG and RTSG. This development would then alert the ASTS registry to the existence of a split and generate queries until data supplied. The ASTS should establish training guidelines and standards for this procedure. The ASTS and UNOS Liver Committees will review donor demographic and clinical data and split recipient patient and graft survival data. One year after implementation, these Committees could assess the results of this policy and make recommendations regarding any needed changes.
The Expanded Donor (by CNS Malignancy and Hepatitis) Work Group
Organs procured from donors with positive viral serology and medical histories of malignancy are currently underutilized. These donors are considered marginal because transplantation of an organ from these donors might transmit disease and thereby compromise the well-being of the recipient. Inherent in cadaveric organ donation is the risk of unintended transmission of viral or neoplastic disease.
In USA, there are approximately 13 000 deaths per year as a result of Central Nervous System (CNS) tumors, yet only about 1.0% of those patients are organ donors. This leaves a significant donor potential, if the risks can be defined. A basic tenet should be that the transplant physician weighs that inherent risk against the possibility that the lack of an organ may result in the death of the recipient (because no organ was available for transplantation). This decision varies by organ type but defining the risk of disease transmission will enhance utilization of organs from these donors.
When considering organ use from donors suffering from intracranial malignancies, there are a number of general guidelines. Most important is to consider the known biologic behavior of various CNS neoplasms and their propensity to spread outside of the cranial vaults. Repeated craniotomy as well as ventriculoperitoneal or ventriculojugular shunts have been associated with increased risk of metastasis.
A list was developed outlining the relative risks as determined by data and known biologic behavior of the tumors (see Table 3). High-risk tumors should be considered for life-threatened allograft recipients.
Table 3. : Risk of CNS tumor transmission from cadaver donor to allograft recipient
• Benign Meningiomas
• Pituitary Adenomas
• Acoustic Schwannomas
• Astrocytoma Grade I
• Epidermoid Cysts, Colloid Cysts
• Low-Grade Oligodendromas
• Gangliogliomas, Gangliocytomas
• Pineocytomas, Ependymomas
• Well Differentiated Teratomas
• Astrocytoma (Grade II)
• Gliomatosis Cerebri
• Anaplastic Astrocytoma (Grade III)
• Glioblastoma Multiforme
• Anaplastic Oligodendroglioma
• Malignant Ependymomas
• Primary Cerebral Lymphomas
Serology Evaluation of an Organ Donor
Table 4 provides guidelines of reliability for the serologic testing, and Table 5 presents the known risks of viral transmission to allograft recipients.
Table 4. : Reliability of serologic testing
Acquisition and consideration of additional data may be helpful in the interpretation of a positive result:
1. Risk factors (ethnicity and social behavior).
2. Titer of hepatitis B core antibody.
3. Result of HBsAb testing.
4. Characterization of HBcAb as IgM.
5. result of HCV Ab testing.
6. Histology of liver biopsy.
Confirmatory testing with antibody neutralization assay is routinely done False negatives may occur with mutant HBV strains (uncommon) False positives may occur immediately after HBV vaccination
Significant false positive rates NO available confirmatory test#
RIBA can improve specificity: performed by some but not all OPOs
Table 5. : Risk of viral transmission
Risk of viral transmission
Data indicate that the risk of viral transmission may be lower for recipients who are immune from previous HBV infection (HBsAb +/HbcAb +) compared to recipients who are immune from vaccination (HBsAb +/HbcAb –).
Although there is evidence that the donor virus is transmitted to the recipient, repopulation after liver transplantation occurs with approximately even frequency by donor or recipient strain. Available data indicate no increase in short (1 year) and medium (5 year) term mortality and morbidity (incidence, timing, or severity of liver disease) associated with transplantation of a liver from a HCVAb + donor vs. a liver from an HCV Ab – donor into a hepatitis C + recipient.
There are insufficient data regarding persistence of donor vs. recipient virus strains after transplantation to determine the true incidence of viral transmission. Available data indicate that transplantation of a kidney from an HCVAb + donor has no adverse impact on graft and patient survival (5 years) or the recipient's HCV disease compared to a kidney from an HCVAb – donor.
If the serology reveals a determination of hepatitis B core Ab +, the simultaneous determination of a hepatitis B s Ab and histological findings consistent with hepatitis ± cirrhosis on liver biopsy, would confirm that the positive hepatitis B core Ab is a true positive. In addition, the class of hepatitis B core positivity, as IgM +, indicates recent infection. Finally, hepatitis B DNA may provide additional information regarding risk of disease transmission, although this use has not been validated by data. The work group proposed that the ideal recipients for kidneys or thoracic organs from hepatitis B core Ab + donors might be those + for HepBsAb. The low risk of disease transmission suggests that a prophylactic treatment strategy may not be warranted. The recipient pool may be justifiably expanded considering the low risk of disease transmission and the availability of effective therapy (Lamivudine). The work group also recommended that all transplant candidates should undergo HepB vaccination. Serologic testing for hepatitis C virus (HCV) is based upon ELISA (EIA) which detects antibodies against HCV antigens. As the sensitivity of anti-HCV EIA has increased, specificity has decreased. In the event of a repeatedly reactive EIA, the recombinant immunoblot assay (RIBA) can help discriminate between a true and false positive result. There is no increase in short- (1 year) and medium- (5 year) term mortality and morbidity (incidence, timing, or severity of liver disease) associated with the transplantation of a liver from a hepatitis C Ab + donor vs. a hepatitis C Ab – donor into a hepatitis C ± recipient. Genotype is only predictive of response to therapy. Genotype does not predict disease severity. Repopulation occurs at equal frequency by donor and recipient genotype. Ideal recipients may be those positive for hepatitis C, although this has not been uniformly held by transplant centers. There is no adverse impact on graft or patient survival 3–5 years after transplantation of a kidney from a hepatitis C Ab + donor into a hepatitis C + recipient compared to a kidney transplanted from a hepatitis C Ab – donor.
The Heart Work Group
The shortage of available donor hearts severely limits clinical cardiac transplantation. For this reason, strict criteria have limited the number of patients placed on the USA waiting list to approximately 6000–8000 per year, though it is estimated that at least 25 000 patients per year would benefit from the procedure. Sub-optimal utilization of donor hearts has compounded the problem in USA. In a 1999 survey from the Association of Organ Procurement Organizations, the average donor yield from 55 regions was 39%, ranging from 19% to 62%.
The primary objectives of the Heart Work Group were to determine the accuracy of current methods to assess donor heart function prior to recovery and to provide recommendations to improve the successful utilization of cardiac donors. The first hypothesis of the heart group was that existing criteria for heart donor suitability can be broadened to increase utilization of marginal donors without compromising recipient outcomes. The second hypothesis was that intensive management of heart donors, including liberal use of pulmonary artery catheterization and hormonal resuscitation, would improve utilization of donors with left ventricular systolic dysfunction and/or hemodynamic instability. The complete recommendations of the Heart Work Group will be published separately.
The heart group proposed modified donor criteria, which have the potential to expand the available pool of cardiac donors. These criteria include donor age, size, left ventricular hypertrophy (LVH), mild valvular disease, and the evaluation of coronary artery disease (CAD). These modifications are described in Table 6. It is important to consider the interactions between the characteristics of the donor heart and the recipient as well as the degree of urgency for the recipient when considering marginal or nonstandard organs.
Table 6. : Crystal City modifications of existing heart donor criteria
Donors > 55 may be used selectively, though coexisting LVH and longer ischemic times may increase recipient mortality risks
Despite an increased risk associated with small donors, a normal sized adult male (> 70 kg) donor is suitable for most recipients
Mild LVH (wall thickness ≤ 13 mm by echocardiography and no LVH by ECG criteria) does not preclude recovery, particularly with shorter ischemic times
Certain lesions, such as mild or moderate mitral or tricuspid regurgitation, or a normally functioning bicuspid aortic valve may be amenable to ‘bench’ repair, prior to transplantation
Certain lesions, such as a secundum type ASD, may be amenable to ‘bench’ repair
a. Male donor age 35–45 years and female donor age 35–50 years: perform angiography if there is a history of cocaine use or ≥ 3 risk factors for CAD
b. Male donor age 46–55 years and female donor age 51–55 years: angiography recommended
c. Age > 55 years: angiography strongly recommended
Donor hearts with mild coronary artery disease should be considered for recipients with relatively urgent need
Although echocardiography is effective in screening for anatomical abnormalities of the heart, the use of a single echocardiogram to determine the physiologic suitability of a donor is not supported by evidence. An alternative approach, using a pulmonary artery catheter to guide the physiologic assessment and management of ventricular dysfunction, has been used with success in UK.
The heart group proposed that metabolic abnormalities, anemia, and excessive dosing of inotropes be corrected prior to obtaining an echocardiogram. Aggressive donor management, including pulmonary artery catheterization and hormonal resuscitation should be performed in all donors with an initial left ventricular ejection fraction less than 45%. If specific hemodynamic criteria can be achieved in these cases, it is appropriate to proceed with recovery. The heart group's specific recommendations for donor management are shown in Figure 7. These recommendations have been adopted into the UNOS Critical Pathway.
The Lung Work Group
The annual number of lung transplants in USA has fluctuated between 850 and 950 for the past 5 years, in a period when the number of thoracic organs recovered from cadaveric donors declined. As the number of patients waiting for lung transplantation continues to increase, there were about two deaths for every three patients who underwent lung transplantation in the year 2000. Variations in OPO practice have been evident by the rates of lung procurement ranging from 7 to 22% of potential donors. Patient selection, patient evaluation, and donor management were cited as important reasons for differences in the utilization of cadaveric lungs. Utilization rates in Canada are higher than in USA. In Australia, lungs from 50% of potential donors have been utilized without compromising recipient outcome. In USA, there is also a utilization variance between small and large centers; smaller centers are defined by fewer than 10 lung transplants per year. Programs transplanting more than 20–25 lungs per year tend to show much higher utilization rates. Wider application of broader criteria for donor selection and procurement is possible and can clearly increase the size of the donor pool. If uniform multidisciplinary donor management protocols were developed, increased lung utilization would follow. Table 7 presents the current criteria that are used to determine the suitability of a cadaver lung donor. The Lung Work Group proposed the new criteria to include virtually any donor with age up to 65 years, absence of lung injury from smoking, and absence of cancer with metastatic potential. The lung group recommended that the OPO coordinator work with the managing physician/thoracic transplant consultant to correct anemia and address fluid status by PA line data, and to employ the hormonal resuscitation as given by Heart Work Group (see Figure 7).
Table 7. : Current criteria for lung donation
The Lung Work Group proposed new criteria to include virtually any donor with age up to 65 years and an absence of lung injury from smoking.
• Absent aspiration, sepsis, or purulent secretions
• Smoking history of < 20 pack years
• Absent history of malignancy
The optimization of donor management and selection criteria should increase the number of potential organ donors (see Table 8). The standardization and simplification of donor management and procurement protocols would benefit all transplant organs and all transplant patients, as the better the cardiopulmonary function of the donor, the better the organ function after transplantation. The Lung Work Group also emphasized the need to improve communication between OPO coordinators and lung transplant centers. The lung group suggested that a plan for regional organ procurement be developed as soon as possible, simplifying the number of transplant center contacts by an OPO and reduce critical delays in waiting for distant procurement teams to arrive when a local procurement team might be able to do the operation. The Lung Work Group also recognized the need to develop outcome research to determine whether prolonged ischemic time or other donor risks may be acceptable. For example, the capacity to augment edema fluid clearance in the lung may be maintained long after the current presumed ‘limit’ of 6 h. Finally, the development of alternative donors, such as non-heart-beating donors should be explored.
Table 8. : Crystal City lung donor management recommendations
Frequent suctioning and aspiration precautions
Albuterol therapy for wheezing (may improve lung fluid clearance)
Richard Freeman Jr MD, Tufts University School of Medicine
Jerry Turcotte MD, University of Michigan
John Rabkin MD, Oregon Health Sciences University
Martin Mozes MD FACS, Regional Organ Bank of Illinois
Dorian Wilson MD, University of Medicine and Dentistry NJ
Beth Fetter RN CPTC, TransLife, Orlando, FL
Monica Johnson-Tomanka MD, OHSU-Portland
Bill Morris, Finger Lakes Donor Recovery Network (NY)
Lynt Johnson MD, Georgetown University Medical Center
Myron Schwartz MD, Mount Sinai Medical Center
Robert Bray MD, Emory University
Marginal Donor Group
Mitchell Henry MD, Ohio State University
Sandy Feng, MD PhD, University of California-San Francisco
Doug Hanto, MD, University of Cincinnati
Kevin O'Connor, New England Organ Bank
Robert Metzger, MD, TransLife
Myron Kauffman MD, UNOS
Joseph Buell MD, University of Cincinnati
Alan Leichtman MD, University of Michigan
Wida Cherik, UNOS Research Department
Norah Terrault MD MPH, University of California-SF
David Roth MD, University of of Miami
Maureen McBride PhD, UNOS
Marc Lorber MD FACS, Yale University
Richard Maters MBA MT, ViroMed Laboratories Inc. (MN)
Mario Deng MD, Columbia University of. College of Phys. & Surgeons
Rick Nolte, Emory University Hospital
Jonathan Zaroff MD, UCSF Medical Center
Bruce Rosengard MD, University of Pennsylvania Medical Ctr
William Armstrong MD, University of Michigan Hospital
Wayne Babcock, BSN, California Transplant Donor Network
Anthony D'Alessandro MD, University of Wisconsin Hospital & Clinics
G William December MD, Massachusetts General Hospital
Niloo Edwards MD, Columbia Presbyterian Medical Ctr
Robert Higgins MD, Medical College of Virginia
Valluvan Jeevanandum MD, University of Chicago
Myron Kauffman MD, UNOS
James Kirklin MD, University of of Alabama Medical Ctr
Stephen Large MD, Papworth Hospital (UK)
Daniel Marelli MD, UCLA Medical Center
Tammie Peterson, RN, Dallas OPO
W Steves Ring MD, UT South-western Medical Ctr
Robert Robbins MD, Stanford University of Sch of Medical
Stuart Russell MD, Duke University of. Medical Center
David Taylor MD, University of Utah Health Sci. Ctr.
Adrian Van Bakel MD, Medical University of South Carolina
John Wallwork, MB, Papworth Hospital (UK)
James Young, MD, Cleveland Clinic Fdn
Edward Garrity Jr. MD, Loyola University Medical Center
Robert Love MD, University of Wisconsin
David Follette MD, University of California Davis Medical Ctr.
Mark Barr MD, University of Southern California
R Duane Davis MD, Duke University of. Medical Ctr
John Conte MD, John Hopkins Hospital
Ken McCurry MD, University of Pittsburgh Medical Center
Marshall Hertz MD, University of Minnesota
Marty Zamora MD, University of Colorado Health Sciences Center
David Weill MD, University of Alabama, Birmigham
John Reilly MD, Brigham and Women's Hospital
Mike Matthay MD, USCF
Paul Nelson MD, St. Lukes Hospital
Rick Hasz, Gift of Life
Meg Rogers RN, LifeSource, Upper Midwest
Curt Tribble, MD, University of Virginia
Bert Trulock MD, Washington University of
Leo Ginns MD, Massachusetts General Hospital
Andrea Zachary MD, Johns Hopkins University of Sch Medical
Stig Steen MD, University Hospital of Lund
Micheal Phillips, Life Connection of Ohio
Peter Buckley PhC, BioPhausia
We thank Gail Durant, Executive Director of the American Society of Transplant Surgeons, for administrative support. Funding/Support: The American Society of Transplantation and The American Society of Transplant Surgeons.