STARZL T E, MARCHIORO T L, PETERS G N, KIRKPATRICK C H, WILSON W E, PORTER K A, RIFKIND D, OGDEN D A, HITCHCOCK C R, WADDELL W R
Transplantation. 1964 Nov;2:752-76. doi: 10.1097/00007890-196411000-00009.
Six patients with terminal uremia due to glomerulonephritis or pyelonephritis were treated with heterografts from East African baboons. Immunosuppressive therapy was provided both before and after operation with azathioprine and prednisone and postoperatively local transplant irradiation and actinomycin C were administered intermittently. The individual rejection episodes in the post-transplant period could be reversed relatively easily but these reemred vigorously and repetitively, making it impossible to relax the stringent requirements of antirejectmion therapy. The continued need for high-dose immunosuppressive therapy precipitated lethal infections in the majority of cases. The patients lived for 19 to 98 days after heterotransplantation. Four died with the baboon kidneys still in placc after 19, 23, 35, and 49 days. In the other two cases the heterografts were removed after 60 and 49 days respectively, at a time when urine excretion was still present, and homografts from volunteer convict donors were placed on the opposite side. Both the latter recipients died of septic complications following the second operation, after 39 and 44 days. Complete cessation of heterograft urine excrelion appeared only in two cases, although rend function was failing in the remainder prior to death or before removal of the heterografts. The relation of renal function to changes in heteroagglutinin and hemagglutinin titers is described. After residence in the host for 19 to 60 days, all the heterotransplants were heavily infiltrated with plasma cells and large lymphoid cells with pyroninophilic cytoplasm. There was also disruption of peritubular capillaries, interstitial edema, widespread tubular damage, swelling of endothelial cells lining arterioles, fibrinoid necrosis of the walls of arterioles and interlobular arteries, and narrowing and obstruction of interlobular arteries by fibrin and platelet deposits on the intima. The pre-glomerular vascular lesions were accompanied by focal infarcts and extensive interstitial hemorrhages. All the pathologic changes were more severe than those seen by Reemtsma in a comparable series of chimpanzee-to-man heterotransplants, where cellular infiltration was slight and vascular lesions uncommon in the presence of major blood group incompatibility between donor and recipient.
6例因肾小球肾炎或肾盂肾炎导致终末期尿毒症的患者接受了东非狒狒的异种移植。术前和术后均使用硫唑嘌呤和泼尼松进行免疫抑制治疗,术后还间歇性地给予局部移植照射和放线菌素C。移植后阶段的个体排斥反应发作相对容易逆转,但这些反应会强烈且反复地再次出现,使得无法放宽抗排斥治疗的严格要求。在大多数情况下,持续需要高剂量免疫抑制治疗引发了致命感染。患者在异种移植后存活了19至98天。4例分别在19、23、35和49天后死亡,狒狒肾脏仍在原位。在另外2例中,异种移植分别在60天和49天后被切除,此时仍有尿液排出,同时在对侧植入了来自志愿罪犯供体的同种移植肾。后2例接受者均在第二次手术后39天和44天死于败血症并发症。仅在2例中异种移植肾完全停止排尿,尽管其余病例在死亡前或异种移植肾切除前肾功能已衰竭。描述了肾功能与异种凝集素和血凝素滴度变化的关系。在宿主中存活19至60天后,所有异种移植肾均被大量浆细胞和具有嗜派洛宁细胞质的大淋巴细胞浸润。还存在肾小管周围毛细血管破坏、间质水肿、广泛的肾小管损伤、小动脉内皮细胞肿胀、小动脉和小叶间动脉壁的纤维蛋白样坏死,以及小叶间动脉因内膜上的纤维蛋白和血小板沉积而狭窄和阻塞。肾小球前血管病变伴有局灶性梗死和广泛的间质出血。所有病理变化均比Reemtsma在一系列类似的黑猩猩与人异种移植中所观察到的更为严重,在后者中,尽管供体和受体之间存在主要血型不相容,但细胞浸润轻微且血管病变罕见。