The Multi-Organ Donor: A Guide to Selection, Preservation and Procurement E-Book
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- Herausgeber: Bentham Science Publishers
- Kategorie: Fachliteratur
- Serie: Current and Future Developments in Surgery
- Sprache: Englisch
Advances in the science of immunology have improved the success rate of organ transplantations since the mid twentieth century. Organ transplantation is now a lifesaving medical procedure for thousands of patients around the world with end-organ diseases.
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Veröffentlichungsjahr: 2018
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PREFACE
“We make a living by what we do, but we make a life by what we give."
- Winston Churchill
The field of organ transplantation has evolved significantly since the first edition of this book was published in 1997. What hasn’t changed is the extraordinary commitment of thousands of healthcare professionals, patients, and most importantly, donor families and loved ones who make the ultimate sacrifice in the face of a devastation loss to give the Gift of Life. These unselfish altruistic acts, which benefit dozens of potential recipients, are the cornerstones of the lifesaving benefits of organ transplantation.
Many healthcare professionals as well make significant personal and professional sacrifices to support the transplant enterprise. Without their commitment, these gifts could not be received. Over 120,000 deserving patients with end-organ failure are awaiting lifesaving or life-enhancing organ transplants. Without the commitment of the multidisciplinary teams, who in some cases have given their lives to procure these organs, the enterprise cannot succeed.
This textbook outlining the best practices in organ procurement and preservation process from world class transplant teams is dedicated to the donors and healthcare professionals who give their lives so that others could live. Special thanks to our families, including spouses, children and support staff at home, who sacrificed and supported our professional aspirations to participate in the transplant enterprise. And special thanks to Elisa Wise for her commitment to this project – which could not have come to fruition without her effort.
List of Contributors
Introduction
Juan A. Sanchez,Robert S.D. Higgins*Abstract
“Know (transplantation) and the whole of medicine is opened to you."
-after Sir William Osler
The story of organ transplantation is one of remarkable achievements punctuated by spectacular breakthroughs in scientific knowledge and surgical techniques. The work of Jaboulay and Carrel in developing vascular anastomosis opened the path to the transplantation of vascularized grafts [1, 2]. The classification of histological rejection by Billingham and work by Medawar and others in immunology and cell biology created opportunities to match organs and recipients to achieve histocompatibility and to modulate the immune system and achieve tolerance as a fundamental goal for graft survival [3, 4]. The introduction of cyclosporine by Calne in 1978 heralded a new age of transplantation medicine with the development of increasingly precise agents to modulate targeted elements of the immune system and considerably extending graft survival [5]. Modern methods of preserving organs ex vivo have expanded the pool of organs and improve graft function. These advancements have catapulted organ transplantation from an option of the last resort to a mainline treatment for end-stage organ failure. However, although challenges continue to exist in these areas, the principal factor limiting transplantation today continues to be the shortage of suitable donor organs.
As a multidisciplinary craft, the field of transplantation touches the entire spectrum of the human experience from the most intricate cellular mechanisms, which distinguish self from foreign tissue to more abstract concepts such as altruism and societal good. It encompasses many psychological, social, economic, and regulatory aspects of human society in order to organize and maintain an
equitable system of organ allocation, develop innovative outcome models, and ensuring the optimal use donor organs.
By the late 1960s, advancements in medical care and technology had improved to the point where the body could be maintained with artificial support long after the brain had irreversibly ceased to function. This required a precise definition of brain death resulting in standard set of neurologic criteria for identifying potential donors [6]. This objective determination of death was a pivotal step in organ donation which allowed retrieval of an organ in a donor before cessation of blood flow thus expanding the pool of organs beyond those which could only be recovered after the heart had stopped beating.
The Uniform Anatomical Gift Act addressing the conditions governing organ donations as well as the National Organ Transplant Act, passed by Congress in 1984, safeguarded the donation process and established a system for equitable allocation of organs to patients needing a transplant. The Social Security Act was amended in 1986 to require healthcare institutions receiving government funds to require requesting the families of potential donors about their options to donate. In 1998, federal legislation required hospitals to notify local organ procurement agencies about potential donors so that their staff could screen potential donors and offer the option of organ and tissue donation if appropriate.
Since the first publication of this book over 20 years ago, the transplant landscape has changed considerably [7]. Among the most significant of the changes is the realization that the success of transplantation is creating an ever-widening gap between demand and supply of donor organs. This has prompted the exploration of other ways to increase the pool of donors such as living organ donation, donation after circulatory death, ex vivo organ circulatory support, partial organ transplants, and mechanical/artificial organs. In addition, there is increasing consideration of organs from donors not previously viewed as suitable due to age and other factors (i.e. Hepatitis C and HIV). As such, selecting and managing potential donors are more important than ever in addition to the need to individualize, allograft selection based on the specific risk profiles of both donor and recipient in order to maximize the equitable allocation of organs and the recipient’s chances for a successful outcome.
CONSENT FOR PUBLICATION
Not applicable.
CONFLICT OF INTEREST
The author declares no conflict of interest, financial or otherwise.
ACKNOWLEDGEMENTS
Declared none.
REFERENCES
[1]Jaboulay M. Greffe du reins au pli du conde par soudures arterielles et veineuses (Kidney grafts in the antecubital fossa by arterial and venous anastomosis). Lyon Med 1906; 107: 575.[2]Carrel A. Results of the transplantation of blood vessels, organs and limbs. JAMA 1908; 51: 1662-7.[http://dx.doi.org/10.1001/jama.1908.25410200010001b] [PMID: 6345837][3]Billingham RE, Brent L, Medawar PB. Actively acquired tolerance of foreign cells. Nature 1953; 172(4379): 603-6.[http://dx.doi.org/10.1038/172603a0] [PMID: 13099277][4]Medawar PB. A second study of the behaviour and fate of skin homografts in rabbits. J Anat 1945; 79: 157-76.[5]Calne RY, White DJ, Thiru S, et al. Cyclosporin A in patients receiving renal allografts from cadaver donors. Lancet 1978 : Dec 23-30;2(8104-5): 1323-7.[6]A definition of irreversible coma. Report of the Ad Hoc Committee of the Harvard Medical School to Examine the Definition of Brain Death. JAMA 1968; 205(6): 337-40.[http://dx.doi.org/10.1001/jama.1968.03140320031009] [PMID: 5694976][7]Higgins RSD, Sanchez JA, Baldwin JC. The Multiorgan Donor: Selection and Management 1997 : January;ISBN-13: 978-0865423954.The Organ Allocation System
Karen Kennedy*,Charles AlexanderAbstract
The following chapters give a succinct reference about how the system is set up, including how organs are listed and allocated and then distributed, for a reader like a resident or fellow trying to understand how organs go from donor to implanted organs, as well as the role of the OPO and what governs your efforts and success.
INTRODUCTION
Organ Procurement Organizations (OPOs) serve an essential role in the coordination of organ donation processes, in partnership with transplant centers and acute care hospitals throughout the United States. Each entity has regulatory, legislative and accreditation requirements, which provide oversight to their respective functions and ensure the utmost safety for potential recipients awaiting solid organ transplants. To best outline these vital roles, a brief review of the legislative and regulatory history of organ donation and transplantation is of value.
Legislative, Regulatory and Accreditation History Highlights
As medical science advanced and solid organ transplantation increasingly became a feasible option for patients in the mid-twentieth century, the need to establish systematic processes for recipient listing and organ allocation became evident to medical professionals and legislators. In 1984, the U.S. Congress enacted the National Organ Transplant Act (NOTA) [1] to address these needs. In 1986, the Federal Omnibus Budget Reconciliation Act was enacted and included language related to developing relevant organ donation and transplantation systems [1]. Highlights of these acts include:
Establishment of the Organ Procurement and Transplantation Network (OPTN), through the Health and Human Resources Administration (HRSA), to maintain a national registry for potential recipient listing organ allocation, administered by a non-profit organization under federal contract [1]Creation of the Scientific Registry of Transplant Recipients (SRTR) [1], also administered through HRSA, to provide statistical and analytic support to the OPTN to help in the formulation and evaluation of organ allocation and other OPTN policies [1]Prohibition on the buying or selling of human organs for transplantation [1]OPO responsibilities in promoting organ donation, identifying potential donors, and recovering and distributing the recovered organs for transplantation [1]Requirements for acute care hospitals to have a working agreement with an OPO [1]As outlined, the NOTA provisions included a mandate for the creation of an Organ Procurement and Transplantation Network (OPTN), facilitated under federal contract through HRSA. The United Network for Organ Sharing (UNOS), based in Richmond, Virginia, was awarded the first contract by the U.S. Department of Health and Human Services in 1986 [2] and has held the contract to this date. Highlights of the services provided by UNOS, as the OPTN contractor, include oversight of: the organ sharing system, equitable and timely allocation of donor organs, and promulgation of donation and transplantation related policies [2].
In collaboration with transplant centers, acute care hospitals, and HLA laboratories throughout the United States, OPOs function as an integral partner in the national organ donation and allocation systems. Their responsibilities are extensively outlined in OPTN/UNOS policies [2]; of particular importance is the scope of clinical activities they facilitate to ensure the safety of organs allocated and, as importantly, to honor the gift of organs provided by donors and their families.
The Centers for Medicaid and Medicare Services (CMS), in its Code of Federal Regulations (CFR), also have oversight of transplant centers, acute care hospitals and OPOs, as outlined in its Conditions of Participation [3]. Highlights include requirements for hospitals to implement protocols with OPOs for timely notification of every individual whose death is imminent or who has died. Extensive OPO performance and outcome metrics are also outlined, monitored and evaluated by CMS. Additionally, these requirements stipulate that OPOs maintain an advisory board with representation that includes, but is not limited to: hospital administrators, intensive care or emergency room personnel, tissue banks, voluntary health associations, histocompatibility experts, neurosurgeons or physicians with neurosciences skills, transplant surgeons from transplant center in OPO’s service area, and donor family members.
CMS also designates, for each OPO, a defined geographic area or “donation service area” (DSA) [3]. OPOs are required by law to have written agreements with each hospital in its DSA, outlining its processes for organ donation, recovery and transplantation. Fig. (2.1) [4] outlines the current CMS defined geographic DSAs.
Fig. (2.1)) Service areas of U.S. organ procurement organizations [4] [from Herdman & Potts, Non-Heart-Beating Organ Donation, 1997, Appendix C]. Medical Illustrations© 2018 Tim Phelps, MS, FAMI, Johns Hopkins University.Uniform Anatomical Gift Act
The Uniform Law Commission (ULC) is a national entity that drafts model legislation for adoption into state laws on subjects for which nationwide uniformity is desirable [5]. The original 1968 Uniform Anatomical Gift Act (UAGA) was promulgated by the ULC to address the emerging regulations and laws being established related to organ and tissue donation across the United States. The original version of this Act was passed and adopted in all 50 states.
In 2006, the scope of the UAGA was revised to reflect changes across the United States related to key aspects of the donation process, to include the order for hierarchy of next of kin and the adoption of electronic signatures. Importantly, the 2006 revised UAGA [5] also strengthened prior language barring others from attempting to override an individual’s decision to make or refuse to make an anatomical gift. Most states passed this legislation, with revisions as indicated, in their respective legislatures.
Among the important highlights of this model legislation [5] are provisions to:
Honor the autonomous decision of individuals who designate their wish to be a donor through a document of giftEstablish the hierarchy for classes of individuals who can give authorization for donationOutline standards that enable donor programs to gain access to documents of gift in donor registries, medical records, and records of the state motor vehicle departmentDefine the circumstances in which a document of gift can be revokedDefine the roles and responsibilities of hospitals in facilitating the referral and donation processesEstablish the responsibilities of hospital providers in giving adequate time to donor programs to evaluate the potential suitability of donors, as well as access to any available medical recordsOrgan Procurement Organization Accreditation Program
The Association of Organ Procurement Organizations (AOPO) is the national non-profit organization representing the current fifty-eight federally designated OPOs [6]. In 1986, standards established by its predecessor were adopted by the Health Care Financing Administration (HCFA) when they instituted a certification process for OPOs [3]. Highlights of AOPO services include: disseminating standards for organ procurement programs, serving as the national accrediting body for OPOs, and facilitating education and research initiatives in collaboration with other healthcare organizations and federal agencies [6].
The accreditation program established by AOPO is integral to maintaining the highest standards of excellence in procurement processes and adherence to all federal laws and regulations. Accreditation, if granted, is provided after a detailed on-site survey and extensive desk audit performed by OPO practice experts. The OPO, if approved, receives accreditation for a three year period [5]; re-accreditation is subsequently required every three years.
Organ Donor Clinical Processes
The preceding historical overview provides a framework for exploring the donation and allocation process in more detail. The responsibilities of an OPO, as outlined by the regulatory and accrediting bodies, are extensive and comprehensive; they extend from the initial hospital referral to follow-up activities once the surgical recovery is complete. Their goal is to ensure organ function is maximized, all suitable organs are transplanted, and safety standards are maintained. The following sections explore specific clinical steps in the process, as illustrated in Fig. (2.2) (7); each OPO and transplant center operationalizes clinical practices in a manner that best meets their program’s needs.
Fig. (2.2)) The Living Legacy Foundation of Maryland clinical process outline [7] [From The LLF training program materials in effect April, 2018]. Medical Illustrations© 2018 Tim Phelps, MS, FAMI, Johns Hopkins University.Referral and Evaluation
In accordance with CMS requirements, every acute care hospital has policies in place which guide staff in making potential donor referrals in a timely manner to their designated OPO [3]. Although policies vary across the United States, each program has triggers, or indicators, for when referrals should be made. The following represents an example of these triggers, as outlined in The Living Legacy Foundation OPO’s Standard Operating Procedures [8]:
Imminent deaths, as defined by the OPO and acute care hospitalPatients with a grave neurological insult, indicated by a Glasgow Coma Score (GCS) of 3-5Patients who have sustained death by cardiac criteriaPrior to the terminal extubation of a patientSituations in which the family initiates the topic of donationWhen donation is a possibility based on the preliminary information provided, the OPO then performs a more comprehensive suitability evaluation. This evaluation is based on an extensive review of available hospital records and assessment of the current clinical treatment plan for the patient. Once initial suitability is determined, the OPO will continue to follow the patient’s clinical course. When evaluating donation potential, there are many considerations [2, 7, 8], to include: age, medical history, neurological status, clinical course and potential for progression to brain death. These factors also assist in determining if a patient meets established criteria for the organ donation after cardiac death (DCD) pathway and/or the organ donation after neurological death pathway.
Authorization Processes
For a patient who meets suitability requirements, the timing for offering the opportunity for donation is determined in a collaborative manner between the healthcare and OPO teams. All families are treated with the utmost respect and sensitivity [7, 8], and ongoing support is offered by the teams throughout the process. Many programs utilize a process known as a huddle, in which the healthcare and OPO teams facilitate a brief and focused discussion (huddle) prior to offering donation options, designed to: discuss family dynamics, determine the legal next of kin, identify if a patient had made a donor designation, and assess appropriate timing and venue for the discussion [7, 8].
Each OPO operationalizes its authorization processes in a manner that meets their unique program needs and is in adherence with all regulatory and accrediting entity requirements. This process includes documentation of the authorization process completed with the next of kin, outlining the organs which have been authorized for transplant, research, education and/or medical therapy. In circumstances where an individual has designated their intent to be a donor through a document of gift as outlined in the UAGA [5], commonly known as first person authorization, the OPO will likewise work closely with the decedent’s next of kin to honor their designation. OPO family services representatives also conduct a comprehensive donor risk assessment interview (DRAI) with the next of kin and any other individuals who may contribute vital information about the donor’s medical and social history [2, 3, 6, 8].
Clinical Donor Management
The donor management process is complex and multi-faceted, encompassing astute assessments and targeted interventions over a broad range of parameters. OPTN/UNOS policies, AOPO standards, OPO practices and transplant center guidelines [2, 3, 6] provide the framework for the clinical management of donors. Each OPO develops clinical management processes to ensure the safety of every organ for waiting recipients. OPTN/UNOS policies offer very detailed outlines for donor related clinical responsibilities; Table 2.1 highlights OPTN/UNOS Policy 2 [2] and shows examples of the diverse scope of OPO related requirements:
AOPO standards and OPTN/UNOS policies [2, 6] outline specific clinical information which must be obtained to evaluate organ function for every donor; in addition, there are specific parameters for a number of organ systems. Often, additional testing or diagnostics may be indicated or requested by the OPO medical director or transplant program. Table 2.2 [2] provides examples of both required and requested information, both through UNOS and at the program’s discretion. This list is not intended to be all encompassing; more detailed information can be found in individual OPO clinical management policy statements [8].
Donor Management Priorities
The donor management phase exemplifies the collaborative nature of OPO, donor hospital and transplant center relationships in maximizing the viability of authorized organs. Clinical goals and objectives are established to optimize organ function, based on OPO policies. Key responsibilities during this phase include performing extensive organ function testing, obtaining all required lab work, and facilitating any indicated diagnostics [2, 6, 8]. Each organ donor case is unique and the OPO team, in consultation with their Medical Director, implements interventions tailored to the donor’s specific clinical needs. Table 2.3 [7] represents an excerpt from an OPO donor management goals worksheet [7]:
Documentation is an essential aspect of the donation process and OPOs utilize clinical databases to record all relevant donor information. This information is ultimately provided to UNOS, which administers the computerized system known as UNet [2]. Through this system, UNOS maintains the list of potential organ recipients and serves as the repository for all organ donor data. With this data, UNOS is able to safely match those recipients with donors in the most equitable manner possible. The next section will explore the organ allocation process in more detail.
Organ Allocation Overview
All solid organs are allocated utilizing OPTN/UNOS policy [2] derived algorithms for each organ system. Specific donor and waiting recipient criterion are programmed into UNet, from which match runs are generated. A match run is a process that filters and ranks waiting list candidates based on this criteria, as well as their medical compatibility with the donor [2]. The candidate list is dynamic, based on factors such as: ABO, time waiting, geographic location, age, and medical urgency.
Each OPO has developed systems by which communication with DSA based and external transplant centers occurs when allocating organs from the match runs. Organ offers are made in a systematic process, following the sequence of candidates on the match run. Specific OPTN derived codes are utilized to document in UNet the acceptance or decline of an organ by the transplant center [2]. This system ensures fairness and equity, by demonstrating OPO and transplant center adherence to following the exact sequence order of potential recipients on the match run.
The following discussion provides a very general overview, by organ system, of adult potential recipient listing criteria and allocation algorithms. For a more extensive review, and for specific details related to pediatric allocation, OPTN/UNOS policies serve as the definitive source [2]. It should also be noted that OPTN/UNOS policies are subject to revisions, as indicated, so referencing the OPTN website ensures access to the most current policy language [2].
Heart and Lung Wait Lists and Allocation: Excerpts from UNOS Policies 6, 10 [2]
The algorithm used to generate heart and lung match run lists are impacted in large measure by these key factors: donor and waiting recipient ABO, height, and weight; geographic location of the potential recipient relative to the donor hospital location; medical urgency; and waiting time. There are also specific considerations given to pediatric patients, depending on the acuity and severity of their illness.
With respect to heart allocation, the match run lists potential recipients based on established algorithms. Allocation for adult donors 18 years of age or older includes numerous classifications, beginning with the following (the full classi- fications list for adult and pediatric donors can be found in UNOS policies [2]:
Classification 1: Candidates in the OPO’s DSA or Zone A (up to 500 miles from the donor hospital) who are adult status 1 or pediatric status 1A and primary blood type match with the donor.Classification 2: Candidates in the OPO’s DSA or Zone A (up to 500 miles from the donor hospital) who are adult status 1 or pediatric status 1A and secondary blood type match with the donor.Classification 3: Candidates in the OPO’s DSA or Zone A (up to 500 miles from the donor hospital) who are adult status 2 and primary blood type match with the donor.All candidates are given a status, which indicates their medical urgency and determines their waitlist sequence, as follows [2]:
Adult Status 1A (patients ≥ 18): In transplant hospital, and has at least one of the following:Mechanical circulatory support via artificial heart, intra-aortic balloon pump, or ECMO deviceContinuous mechanical ventilationContinuous infusion of single high-dose or multiple intravenous inotropes (blood pressure agents)OR
May or may not be in transplant hospital, and has at least one of the following: VAD (ventricular assist device) or mechanical support with significant complicationsAdult Status 1B (patients ≥ 18); Patient has at least one of the following:VAD (ventricular assist device) or continuous infusion of intravenous inotropesAdult Status 2 (patients ≥ 18): Patient who does not meet criteria for 1A or 1B but suitable for transplantWith respect to lung allocation, the following considerations are integral to the process [2]:
For potential recipients ages 12 and above, select medical information is gathered to calculate a lung allocation score (LAS), which stratifies the severity of illness on a scale from 0 to 100All candidates are placed in order for compatible lung offers, according to their score, within a 250 nautical mile circle around the donor hospital, and then in broader geographic zones, in a similar fashion to the heart allocation algorithmPediatric recipients < 12 years of age are assigned priority for allocation based on medical urgencyLiver Wait List and Allocation: Excerpts from UNOS Policy 9 [2]
With respect to liver allocation the match run lists potential recipients according to established algorithms. Allocation for adult donors 18 years of age or older also includes numerous classifications, beginning with the following (the full classifications list for adult and pediatric donors, as well as any regional variations, can be found in UNOS policies [2]:
Classification 1: Candidates in the OPO’s region who are adult or pediatric status 1AClassification 2: Candidates in the OPO’s region who are pediatric status 1BEach waiting recipient is assigned a MELD (Model for End-Stage Liver Disease) or PELD (Pediatric End-Stage Liver Disease) score. This score is derived based on lab levels and other clinical factors. Liver candidates at least 18 years old at the time of registration may be assigned any of the following: Adult status 1A, Calculated MELD score, Exception MELD score or Inactive status [2]. Highlights of these priorities include [2]:
Adult Status 1A (patients ≥ 18): Patient has at least one of following, with life expectancy < 7 days [2]:Fulminant liver failure or anhepatic statePrimary non-function of a transplanted liver within 7 daysHepatic artery thrombosis in a transplanted liver within 7 daysAcute decompensated Wilson's diseaseIntestine Allocation Algorithm: Excerpts from UNOS Policy 7 [2]
The algorithm used to generate a match run for an intestine is based on these key factors: donor and recipient ABO; recipient's waiting time; medical urgency; and geographic location of recipient relative to donor hospital [2].
Geographic Location [2]
For intestine allocation, geographic location of recipients is always prioritized in this order [2]:
Local transplant centersThe OPO's OPTN/UNOS regionNationally, to other regionsMedical Urgency [2]
All candidates on the intestine waitlist are given a status that indicates their medical urgency.
Status 1: candidates with any of the following conditions [2]:
Liver function test abnormalitiesRestriction of intravenous feeding due to absence of vascular accessUrgent medical indications for an intestinal organ transplantStatus 2: Any candidate that does not meet requirements for Status 1
Additional Considerations
Potential recipients may be listed for the intestine alone or for multiple organs, such as liver, stomach, and/or pancreas. It is important to note that candidates for combined liver-intestine transplants must be matched by using the liver match run [2].
Kidney Wait List and Allocation: Excerpts from UNOS Policy 8 [2]
The kidney algorithm is known as the Kidney Allocation System (KAS). This algorithm is designed to make more kidneys available for transplant and increase the years of life gained per transplanted kidney. The UNOS algorithm [2] weighs the following factors:
Donor and recipient blood typeDonor's Kidney Donor Profile Index (KDPI) scoreRecipient's Expected Post Transplant Survival (EPTS) scoreRecipient's Calculated Panel Reactive Antibody (CPRA) percentageRecipient's Kidney Allocation Points scoreAntigen mismatch between the donor and recipientGeographic proximity of the donor and recipientKDPI Score [2]
Each kidney offered for transplant is given a KDPI score from 0% to 100%, representing the kidney's projected longevity in comparison to other kidneys. This percentage is calculated based on the Kidney Donor Risk Index (KDRI) score [2], which considers: donor age; height; weight; ethnicity; serum creatinine level; Hepatitis C status; whether cause of death is a stroke; type of donor; and past medical history of diabetes or hypertension.
Based on this scoring system, kidneys in the upper range of function have lower KDPI percentages [2]. For example: A KDPI of 35% indicates that out of 100 kidneys, the kidney being allocated is expected to function for a longer period of time than the other 65 kidneys.
EPTS Score [2]
An EPTS score is assigned to all candidates 18 years of age and older. It incorporates four measurements: time candidate’s age, dialysis status, current diabetes diagnosis and history of previously organ transplants. The score indicates the patient’s expected survival time after transplant. A lower score represents an expected longer survival time. Candidates with longer than expected survival times generally are matched to kidneys that are expected to function longer and which have lower KDPI scores [2].
CPRA Percentage [2]
The candidate's CPRA percentage represents the number of HLA antibody reactions they have when their serum is tested against white blood cells from a panel of approximately 100 area blood donors. The lower the CPRA, the less reaction the candidate’s blood has to samples from the panel [2
