Early and late injury to renal transplants from non-heart-beating donors.

ABSTRACT

BACKGROUND: The lack of adequate numbers of kidneys for transplantation has stimulated interest in the use of organs from non-heart-beating donors (NHBDs). The short- and long-term effects of this risk factor on kidney isografts and allografts were examined with a rat model. METHODS: NHBDs were killed by ether overdose. Kidney isografts (male Lewis rats [LEW]-->LEW) were transplanted orthotopically into bilaterally nephrectomized recipients 15, 30, 45, and 90 min after asystole to determine short-term survival patterns, which were compared to those of rats bearing kidneys from living donors (LDs, 0 min). Isografts and allografts (Fisher 344 rats-->LEW) from 45-min and 105-min NHBDs and from LD controls were placed in additional recipients in which contralateral native nephrectomy was performed on day 10 to allow the injured graft to recover from its ischemic insult. Serum creatinine, proteinuria, and graft morphology were assessed serially over a 24-week follow-up period. RESULTS: Early survival and renal dysfunction of isografted rats correlated with the interval of donor cardiac arrest before transplantation. Long-term survival of recipients of kidneys from LDs and between 45-min and 105-min NHBDs was also significantly different (100% vs. 87% vs. 37% at 24 weeks, respectively, P<0.03). Proteinuria increased progressively over time, proportionate to the period of donor asystole, and was associated with increasing cellular infiltration, tubular atrophy, and glomerulosclerosis in the grafts. The development of important functional and structural changes was intensified in NHBD allografts. LD allografts showed early changes of chronic rejection. CONCLUSIONS: The results emphasize the continuum between an initial nonspecific, donor-associated renal injury and late functional and morphologic changes associated with the interval of donor cardiac arrest. These events are accelerated in NHBD allografts that experience the added insult of host alloreactivity.