The Science of Deceased Donor Kidney Transplantation

Kevin J. O’Connor

Francis L. Delmonico

H. Albin Gritsch

Gabriel M. Danovitch

Kidney transplantation cannot proceed without kidney donors, and although much emphasis is justifiably given to post-transplantation patient management, the appropriate identification and preparation of both living and deceased donors contribute critically to the success of the transplantation endeavor on the individual, national, and international levels. As of 2009, living donors and deceased donors each account for about half of all kidney transplantations performed in the United States. Although most transplantation centers regard living donation as the preferred donation modality for individual patients with advanced kidney disease, the therapeutic potential of deceased organ donation must be maximized not only for kidneys but also for other solid organs for which living donation is not an option (or a limited option in the case of liver transplantation). Efforts to enhance deceased donor transplantation are essential to minimize the burden on living donors and on recipients who do not have the option of living donation (see Appendix, Declaration of Istanbul).

There are wide variations in the use of living and deceased kidney donors around the world (see Chapter 1, Fig. 1.3). These differences reflect varying medical and societal cultural values and varying realities in the availability of sophisticated care for patients with advanced kidney disease (see Chapter 1, Fig. 1.2). Differences can also be driven by the availability of deceased donor organs relative to the number of patients waiting for transplants, attitudes of local physicians regarding the risks of living donation, national deceased donor legislation, and the degree of government oversight. In Spain, for example, where a highly effective mechanism for identifying deceased donors has helped keep waiting lists short, living donation accounts for less than 5% of all transplantations. In Japan, however, strong cultural and, until recently, legal barriers have limited deceased donor transplants, resulting in living donation as the most common form of transplantation.

In the United States, the supply of deceased organ donors and kidneys has increased. There were close to 11,000 deceased donor kidneys transplanted in 2009, an increase of 25% over the previous 5 years. Much of this increase has been attributed to the effectiveness of the Organ Donation and Transplantation Breakthrough Collaborative sponsored by the Health Resources and Services Administration (HRSA). Despite this large increase in the supply of deceased donor kidneys in this “Collaborative era,” the total number of renal transplant candidates on the waiting list continues to increase each year and reached about 80,000 as of early 2009. The rate of expansion of the list reflects the number of new registrants minus the number of patients who receive transplants from living and deceased donors and the number of patients who die while awaiting a transplant or who are removed from the list for other reasons. About one third of those registered, however, are listed as “inactive” and therefore deemed ineligible for transplantation at a given point in time (see Chapter 7,
Part II). Currently, the number of transplants performed each year approximates the number of new “active” candidates on the list.

TABLE 4.1 Deceased Donor Process: From Donor Identification to Transplantation

Donor identification

Imminent death—eligible death

Referral to organ procurement organization

Assessment of donor suitability

Consent for donation

Organ donor intensive care unit management

Organ allocation

Organ recovery surgery

Organ preservation and transportation

Organ transplantation

This chapter addresses the various aspects of deceased donor kidney transplantation. The term science of deceased organ donation was adopted to capture the nuanced complexity of its medical, ethical, organizational, and societal aspects and to reflect on the fact that we have much to learn about how to optimize the procedure. The chapter is divided into three parts. The first part addresses the selection and preparation of deceased donors; the second part addresses the surgical technique of deceased organ donation and organ preservation; and the third part addresses the allocation of deceased donor kidneys to the kidney transplant waiting list.

PART I. DIAGNOSIS OF DEATH AND IDENTIFICATION, SELECTION, AND PREPARATION OF DECEASED DONORS

The deceased donor organ donation process can be viewed as a continuum from the first identification of the potential organ donor through to the transplantation of renal (and other) allografts at the transplantation center (Table 4.1). To maximize the supply and quality of the deceased donor kidney pool, every step in this continuum needs to be optimized, as described next.

Diagnosis of Death

Traditionally, in the lay, legal, and medical communities, death has been determined by an irreversible cessation of cardiac and respiratory function. The concept of brain death emerged in the 1960s as a response to the ability to resuscitate individuals and mechanically maintain cardiac and respiratory function. The terms brain death and cardiac death are employed in this chapter because of their widespread use and familiarity. These terms are not ideal and may be a source of confusion and distress in the lay community and among donor families because of understandable but unsubstantiated concern that brain-dead donors are not truly dead. The terms death determined by neurologic criteria and death determined by cardiorespiratory criteria are preferable.

Diagnosis of Brain Death

Most organ donors have severe brain injury and present to the hospital with a low Glasgow Coma Scale score (Table 4.2). Most deceased organ donors are brain dead. Proper diagnosis of brain death is essential to the organ donation process
and to maintaining public trust and acceptance of organ donation from brain-dead organ donors. Among the lay public, there is often a troubling confusion between the diagnosis of brain death and that of a persistent vegetative state. The criteria for diagnosis and declaration of brain death are well described (Table 4.3) and require irrefutable documentation. They include a known cause of brain injury, irreversibility, and absence of cerebral and brainstem function, including apnea. The diagnosis of brain death should be made by a physician who is independent of the transplantation team and thus free of conflict of interest. Ancillary testing is not mandated but may include electroencephalography, conventional angiography, radionuclide angiography, magnetic resonance angiography, computed tomographic angiography, transcranial Doppler, and somatosensory evoked potentials. Indications for pursuit of ancillary testing include toxic drug levels, inconclusive apnea testing, normal neuroimaging, inability to complete a clinical examination, and chronic CO₂ retention.

TABLE 4.2 Glasgow Coma Scale

Response	Score^*
Eyes Open
Spontaneous	4
To speech	3
To pain	2
Absent	1
Verbal
Converses, is oriented	5
Converses, is disoriented	4
Inappropriate	3
Incomprehensible	2
Absent	1
Motor
Obeys	6
Localizes pain	5
Withdraws (flexion)	4
Decorticate (flexion) rigidity	3
Decorticate (extension) rigidity	2
Absent	1
^*The sum obtained in this scale is used to assess coma and impaired consciousness: mild is 13 to 15 points; moderate is 9 to 12 points; severe is 3 to 8 points. Patients with a score of less than 8 are in a coma.
(From Teasdale G, Jennet B. Assessment of coma and impaired consciousness: a practical scale. Lancet 1974;304:81-84, with permission.)

Diagnosis of Cardiac Death

The term donation after cardiac death (DCD) is preferred to the term non-heart-beating donor (NHBD) because of the parallel to the more common donation after brain death. Before the acceptance of criteria for the declaration of brain death, all deceased donor organs were recovered from patients with cardiac arrest. With the broad acceptance of brain death criteria and the development of multiorgan recovery, the use of DCD organs decreased substantially because
of the risks associated with ischemic damage. The organ donor shortage has led to a reevaluation of this policy.

TABLE 4.3 Clinical Criteria for Diagnosis of Brain Death

Irreversibility
	No sedating, paralyzing, or toxic drugs
	No gross electrolyte or endocrine disturbances
	No profound hypothermia
Absent Cerebral Function
	No seizures or posturing
	No response to pain in cranial nerve distribution^*
	Absent brainstem function
	Apnea in response to acidosis or hypercarbia
	No pupillary or corneal reflexes
	No oculocephalic or vestibular reflexes
	No tracheobronchial reflex
^*Spinal reflexes may be present.

There has been a steady increase in the fraction of DCD donors in the United States (see Fig. 4.1). There are four so-called Maastricht categories of DCD donors (Table 4.4). Category I and II DCD donors, also referred to as uncontrolled donors, are pulseless and asystolic after adequate but failed attempts at resuscitation. Some trauma centers have developed protocols to minimize ischemia in these circumstances by rapid placement of intravenous cannulas to cool the organs after death has been declared. The option to donate is preserved until the family can be informed of the death and then counseled by the organ procurement staff. If consent to donate is obtained, the organs are recovered quickly to prevent further ischemic injury.

Uncontrolled DCD is the most common form of DCD in Spain and Japan. In the United States, DCD is usually category III or “controlled.” These donors are comatose, irreversibly brain damaged, and respirator dependent, but are not brain dead by strict definition. In these circumstances, the decision to withdraw supportive care is made by the family and primary medical team, and appropriate consent for organ donation is obtained after the decision to withdraw support. Ventilator support is discontinued either in the operating room or in an intensive care unit, cardiac function is monitored, and death is pronounced by standard cardiac criteria after a predetermined (usually 5-minute) period of asystole. Organ recovery then proceeds expeditiously. The organ recovery team plays no part in the diagnosis of death or medical management of the patient before asystole. Maastricht category IV DCD donors are also known as “crashing donors,” who have often become hemodynamically unstable en route to organ recovery after a diagnosis of brain death.

It has been estimated that if DCD protocols were maximized, the supply of deceased donor organs could increase considerably. DCD is associated with an increased rate of delayed graft function, but long-term graft survival is similar to that of brain-dead donors. It is critical that protocols for DCD be ethically sound, respect the feelings of donor families and medical staff, and avoid any appearance of conflict of interest. As of 2007, all organ procurement organizations (OPOs) and transplant centers in the United States must develop and comply
with protocols to facilitate recovery of organs by DCD. The model elements of DCD protocols are summarized by Steinbrook (see “Selected Readings”).

FIGURE 4.1 Deceased donor population by donor type and year in the United States. (From Sung RS, Galloway J, Tuttle-Newhall J, et al. Organ donation and utilization in the United States 1997-2006. Am J Transplant 2008;8(Pt 2):922-934, with permission.)

Donor Identification and Referral

Prompt identification of all potential organ donors is critical to efforts to maximize organ donation and transplantation. Potential organ donors may be identified in the emergency department or in the critical care unit. Most deceased organ donors have suffered severe nonsurvivable brain injury, traumatic or otherwise, and are first seen in the emergency department, then transferred to the intensive care unit. A small subset of potential DCD donors present with terminal respiratory failure or end-stage neurodegenerative disease such as amyotrophic lateral sclerosis. Vigilant surveillance for potential organ donors on the part of emergency and critical care staff is paramount to ensure that every opportunity is realized. In the United States, hospitals are required by the Center for Medicare and Medicaid Services (CMS) to identify and refer all potential organ donors to the local OPO. The term imminent death has been used to define those patients who should be referred to the OPO as one of several performance metrics routinely monitored by CMS (Table 4.5).

TABLE 4.4 Maastricht Categories for Non-Heart-Beating Donors

Category I: dead on arrival

Category II: unsuccessful resuscitation

Category III: awaiting cardiac death

Category IV: cardiac death in a brain-dead donor

TABLE 4.5 Definition of Imminent Death

A patient with severe, acute brain injury, who:
	1.	Requires mechanical ventilation, and
	2.	Is in an intensive care unit or emergency department, and
	3.	Has clinical findings consistent with a Glasgow Coma
Scale score that is less than or equal to a mutually agreed on threshold (e.g., 4 or 5); or
		For whom physicians are evaluating a diagnosis of brain death; or
		For whom a physician has ordered that life-sustaining therapies be withdrawn, pursuant to the family’s decision.
(Adapted from Shafer TJ, Wagner D, Chessare J, et al. Organ Donation Breakthrough Collaborative: increasing organ donation through system redesign. Crit Care Nurse 2006;26:33-48.)