Influence of donor brain death on chronic rejection of renal transplants in rats

The clinical observation that the results of kidney grafts from living dono rs (LD), regardless of relationship with the host, are consistently superio r to those of cadavers suggests an effect of brain death (BD) on organ qual ity and function. This condition triggers a series of nonspecific inflammat ory events that increase the intensity of the acute immunologic host respon ses after transplantation (Tx). Herein are examined the influences of this central injury on late changes in renal transplants in rats. A standardized model of BD was used. Groups included both allografts and isografts from n ormotensive brain-dead donors and anesthetized LD. Renal function was deter mined every 4 wk after Tx, at which time representative grafts were examine d by morphology and by reverse transcriptase-PCR. Long-term survival of bra in-dead donor transplants was significantly less than LD grafts. Proteinuri a was significantly elevated in recipients of grafts from BD donors versus LD controls as early as 6 wk postoperatively and increased progressively th rough the 52-wk follow up. These kidneys also showed consistently more inte nse and progressive deterioration in renal morphology. Changes in isografts from brain-dead donors were less marked and developed at a slower tempo th an in allografts but were always greater than those in controls. The transc ription of cytokines was significantly increased in all brain-dead donor gr afts. Donor BD accelerates the progression of long-term changes associated with kidney Tx and is an important risk factor for chronic rejection. These results explain in part the clinically noted difference in long-term funct ion between organs from cadaver and living sources.