Tanabe K, Takahashi K, Sonda K, Tokumoto T, Ishikawa N, Kawai T, Fuchinoue S, Oshima T, Yagisawa T, Nakazawa H, Goya N, Koga S, Kawaguchi H, Ito K, Toma H, Agishi T, Ota K
Department of Urology, Kidney Center, Tokyo Women's Medical College, Japan.
Transplantation. 1998 Jan 27;65(2):224-8. doi: 10.1097/00007890-199801270-00014.
Despite great efforts to promote the donation of cadaveric organs, the number of organ transplantations in Japan is not increasing and a serious shortage of cadaveric organs exists. These circumstances have forced a widening of indications for kidney transplantation. For this purpose, ABO-incompatible living kidney transplantations (LKTs) have been performed. Although we have already reported the short-term results of ABO-incompatible LKT, there is no report of long-term results in such cases; anti-A and anti-B antibodies could cause antibody-induced chronic rejection and result in poor long-term graft survival. In this study, we have reviewed the long-term results of ABO-incompatible LKT and tried to identify the most important factors for long-term renal function in ABO-incompatible LKT.
Sixty-seven patients with end-stage renal failure underwent ABO-incompatible living kidney transplantation at our institute between January, 1989, and December, 1995. The mean age was 34.9 years (range, 8-58 years), with 38 males and 29 females. Incompatibility in ABO blood group antigens was as follows: A1-->O, 23 patients; B-->O, 19 patients; A1B-->A1, 7 patients; B-->A1, 8 patients; A1-->B; 4 patients; A1B-->B, 4 patients; A1B-->O, 2 patients. The number of HLA-AB, and -DR mismatches were 1.6+/-1.1 and 0.76+/-0.6, respectively. Plasmapheresis and immunoadsorption were carried out to remove the anti-AB antibodies before the kidney transplantation. In the induction phase, methylprednisolone, cyclosporine, azathioprine, antilymphocyte globulin, and deoxyspergualin were used for immunosuppression. Local irradiation of the graft was performed at a dose of 150 rad, on the first, third, and fifth days after transplantation. Splenectomy was done at the time of kidney transplantation in all cases.
Patient survival was 93% at 1 year and 91% at 8 years. Graft survival was 79% at 1, 2, 3, and 4 years, 75% at 5 and 6 years, and 73% at 7 and 8 years. Patient survival was not significantly different from that of ABO-compatible patients. However, graft survival was significantly different between ABO-incompatible grafts and ABO-compatible grafts. Specifically, ABO-incompatible transplant recipients experienced a significantly higher rate of early graft loss up to 3 years but showed an equivalent graft loss by year 4. Among 67 patients, 16 grafts were lost during the observation period. Loss was due to acute rejection in 5 patients, followed by chronic rejection in 5 patients and death with function in 3 patients, whereas immunosuppression was withdrawn in 3 patients due to nonimmunological reasons. Of 16 grafts lost, 15 were lost within 1 year after transplantation. Of the 67 patients, 5 died during observation. Three patients with functioning grafts died of uncontrolled bleeding due to duodenal ulcer, malignant lymphoma, and cerebral hemorrhage (one patient each). One patient died of ischemic colitis due to secondary amyloidosis and one patient of cerebral hemorrhage after graft loss due to humoral rejection. There was no fatal infectious complication, whereas 10 patients had non-tissue-invasive cytomegalovirus infection. The stepwise logistic regression model was employed to identify the most important factors for long-term renal function. Patients were subdivided into those with serum creatinine of less than 2.0 mg/dl (group 1, n=39) versus those with serum creatinine of more than 2.0 mg/dl (group 2, n=22) at one year after renal transplantation. Six patients were excluded because of death with functioning graft (three patients) and withdrawal of immunosuppression (three patients). Rejection episodes within 6 months were significantly frequent in group 2 compared with group 1 (P=0.0008). Odds ratio was 112-fold in the rejection episodes. Obviously, the high incidence of early humoral rejection is caused by ABO incompatibility, because ABO-incompatible grafts experience a higher rate of early rejection and graft loss compa
尽管为促进尸体器官捐赠付出了巨大努力，但日本的器官移植数量并未增加，尸体器官严重短缺。这些情况迫使肾移植的适应证范围扩大。为此，已开展了ABO血型不相容的活体肾移植（LKT）。尽管我们已经报告了ABO血型不相容LKT的短期结果，但尚无此类病例长期结果的报告；抗A和抗B抗体可能导致抗体介导的慢性排斥反应，并导致长期移植物存活不佳。在本研究中，我们回顾了ABO血型不相容LKT的长期结果，并试图确定ABO血型不相容LKT中长期肾功能的最重要因素。
1989年1月至1995年12月期间，67例终末期肾衰竭患者在我院接受了ABO血型不相容的活体肾移植。平均年龄为34.9岁（范围8 - 58岁），男性38例，女性29例。ABO血型抗原不相容情况如下：A1→O，23例；B→O，19例；A1B→A1，7例；B→A1，8例；A1→B，4例；A1B→B，4例；A1B→O，2例。HLA - AB和 - DR错配数分别为1.6±1.1和0.76±0.6。在肾移植前进行血浆置换和免疫吸附以去除抗AB抗体。在诱导期，使用甲基泼尼松龙、环孢素、硫唑嘌呤、抗淋巴细胞球蛋白和去氧精胍进行免疫抑制。移植后第1、3和5天对移植物进行150拉德剂量的局部照射。所有病例均在肾移植时进行脾切除术。
1年时患者生存率为93%，8年时为91%。移植物生存率在1、2、3和4年时为79%，5和6年时为75%，7和8年时为73%。患者生存率与ABO血型相容患者无显著差异。然而，ABO血型不相容移植物与ABO血型相容移植物的移植物生存率有显著差异。具体而言，ABO血型不相容的移植受者在3年内早期移植物丢失率显著更高，但到第4年时移植物丢失率相当。在67例患者中，观察期内有16例移植物丢失。5例因急性排斥反应丢失，其次5例因慢性排斥反应丢失，3例因移植肾功能存活时死亡，而3例因非免疫原因停用免疫抑制剂。在16例丢失的移植物中，15例在移植后1年内丢失。67例患者中，5例在观察期内死亡。3例移植肾功能存活的患者分别死于十二指肠溃疡、恶性淋巴瘤和脑出血导致的无法控制的出血（各1例）。1例因继发性淀粉样变性导致缺血性结肠炎死亡，1例在因体液排斥反应移植物丢失后死于脑出血。无致命性感染并发症，而10例患者有非组织侵袭性巨细胞病毒感染。采用逐步逻辑回归模型确定长期肾功能的最重要因素。将肾移植后1年时血清肌酐低于2.0mg/dl的患者分为第1组（n = 39），血清肌酐高于2.0mg/dl的患者分为第2组（n = 22）。6例患者因移植肾功能存活时死亡（3例）和停用免疫抑制剂（3例）被排除。与第1组相比，第2组在6个月内的排斥反应发作明显更频繁（P = 0.0008）。排斥反应发作的优势比为112倍。显然，早期体液排斥反应的高发生率是由ABO血型不相容引起的，因为ABO血型不相容的移植物早期排斥反应和移植物丢失率更高。
