Pratschke Johann, Wilhelm Markus J, Laskowski Igor, Kusaka Mamoru, Beato Francisca, Tullius Stefan G, Neuhaus Peter, Hancock Wayne W, Tilney Nicholas L
Surgical Research Laboratory, Harvard Medical School, Boston, Massachusetts.
Department of Pathology, Harvard Medical School, Boston, Massachusetts.
J Am Soc Nephrol. 2001 Nov;12(11):2474-2481. doi: 10.1681/ASN.V12112474.
The clinical observation that the results of kidney grafts from living donors (LD), regardless of relationship with the host, are consistently superior to those of cadavers suggests an effect of brain death (BD) on organ quality and function. This condition triggers a series of nonspecific inflammatory events that increase the intensity of the acute immunologic host responses 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 normotensive brain dead donors and anesthetized LD. Renal function was determined every 4 wk after Tx, at which time representative grafts were examined by morphology and by reverse transcriptase-PCR. Long-term survival of brain-dead donor transplants was significantly less than LD grafts. Proteinuria was significantly elevated in recipients of grafts from BD donors versus LD controls as early as 6 wk postoperatively and increased progressively through the 52-wk follow up. These kidneys also showed consistently more intense and progressive deterioration in renal morphology. Changes in isografts from brain-dead donors were less marked and developed at a slower tempo than in allografts but were always greater than those in controls. The transcription of cytokines was significantly increased in all brain-dead donor grafts. 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 function between organs from cadaver and living sources.
临床观察发现，活体供者（LD）的肾移植结果，无论与宿主的关系如何，始终优于尸体供者的肾移植结果，这表明脑死亡（BD）对器官质量和功能有影响。这种情况会引发一系列非特异性炎症事件，增加移植（Tx）后急性免疫宿主反应的强度。本文研究了这种中枢性损伤对大鼠肾移植后期变化的影响。使用了标准化的BD模型。研究组包括来自血压正常的脑死亡供者和麻醉的LD的同种异体移植和同基因移植。Tx后每4周测定一次肾功能，此时通过形态学和逆转录聚合酶链反应对代表性移植物进行检查。脑死亡供者移植的长期存活率明显低于LD移植物。与LD对照组相比，BD供者移植物受者的蛋白尿早在术后6周就显著升高，并在52周的随访中逐渐增加。这些肾脏在肾形态学上也始终表现出更严重和渐进性的恶化。脑死亡供者同基因移植的变化比同种异体移植更不明显，发展速度也更慢，但总是大于对照组。所有脑死亡供者移植物中细胞因子的转录均显著增加。供者BD加速了与肾Tx相关的长期变化的进展，是慢性排斥反应的一个重要危险因素。这些结果部分解释了临床上观察到的尸体供者和活体供者器官长期功能的差异。
