BRAIN DEATH AND ITS INFLUENCE ON DONOR ORGAN QUALITY AND OUTCOME AFTER TRANSPLANTATION1

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Abstract
Transplantation has evolved as the treatment of choice for many patients with end-stage organ disease. However, despite the >80% one-year functional survival rate of most transplanted organs at the present time, the ultimate goal-to provide long-term treatment for an irreversible process-has not been achieved; the rate of attrition over time has not changed appreciably throughout the entire experience (1). Although recurrent disease, de novo infections, malignancies, and other factors may contribute to late graft deterioration, chronic rejection remains the most important etiologic factor (2). Despite well-characterized functional and morphological changes, the mechanisms leading to this progressive state remain poorly understood. Its pathophysiology has been conceptualized as stemming from both antigen-dependent and -independent risk factors (3). Although immune-mediated events are considered to be primarily responsible for the late graft changes, it seems increasingly that the influence of nonimmunological events has been underestimated. This concept has been emphasized by recent pooled United Network of Organ Sharing data that show that the survival rates of kidneys from living-unrelated and one haplotype-matched living-related donors are identical despite potentially important differences in genetic relationship with the given recipient (4). In addition, organs from all living donors demonstrate consistently superior results to those from cadaver sources over both the short- and long-term. Various nonimmunological factors that might explain these discrepancies include the effects of initial ischemia/reperfusion injury, inadequate functioning nephron mass, viral infections, and drug toxicity. Brain death is a rarely considered risk factor uniquely relevant to the cadaver donor. Multivariate analysis has emphasized that both initial and long-term results of engrafted cadaver organs may be dependent upon donor demographics and the etiology of the central injury (5). In virtually all experimental studies of organ transplantation, young, healthy living animals are used as donors; in clinical practice, in contrast, a relatively low percentage of organs comes from living donors, as cadavers remain the primary source of supply. Amongst other variables, the difference between the two donor populations implies the effect of profound physiological and structural derangements that may occur during and subsequent to brain death and before the actual engraftment procedure.