Mota Alfredo
Serviço de Urologia e Transplantação, Hospitais da Universidade de Coimbra.
Acta Med Port. 2004 Jan-Feb;17(1):8-14. Epub 2004 Feb 27.
The aim of this study was to study the incidence and causes of acute rejection (AR) on cadaveric renal transplants under cyclosporine A-based immunosuppression, and to investigate the AR effect on the ocurrence of chronic dysfunction (CD) and on the outcome of transplantation.
We analyzed 794 renal transplants from cadaver donor between December, 1985 and December, 1999. We examined the major donor, recipient and graft-related factors and their influence in graft outcome. The diagnosis of AR was in 65% based in clinical and laboratorial findings: fever, decrease of diuresis, graft pain and/or strained and a serum creatinine increase of at least 0,4 mg/dl, and in 35% the diagnosis of AR was biopsy-proven. Statistics included univariate and multivariate analysis. Graft and patient survival rates were calculated by Kaplan-Meier method (with log-rank test).
In the 794 renal transplants included in the study, 498 (63%) didn't have AR and 296 (37%) had at least one episode of AR. This overall incidence of AR of 37% is decreasing and in the last two years, 1998 and 1999 remained in 24% and 25%, respectively. The AR was associated with cadaver donor-related factors [ non traumatic cause of death (p=0,018), perfusion with Eurocollins solution (p=0,008) and cold ischemia time > 24 hours (p= 0,032)] and with recipient-related factors [age < 45 years (p=0,000) and immunosuppression with antithymocyte globulin (ATG) + azathioprine (Aza) + prednisone (Pred) + cyclosporine A (CsA) (p=0,006)]. Concerning graft-related factors acute tubular necrosis (ATN) was related with higher incidence of AR (35% of AR without ATN versus 48% of AR with ATN, p= 0,008) and this, was responsible by a significative increase of chronic dysfunction (CD) (p= 0,000) and by the worst graft function at the end of the first year (p= 0,000). Our results also showed that CD as a cause of graft loss increased substantially (23% vs 49%) in the presence of AR. The 1, 3, 5, 10 and 15-year graft survival in the patients with AR were, 94%, 85%, 74%, 50% and 38%, respectively, and in the patients without AR, 97%, 91%, 87%, 77% and 67%, respectively. These results were statistically significant ( p= 0,000). The AR didn't influence patient survival (p= 0,814).
Our overall incidence of AR (37%) is decreasing reaching in the last year 25%. The AR incidence increased significantly with grafts from cadaver donors with non-traumatic cause of death, preserved with Eurocollins solution, with cold ischemia times > 24 hours and in recipients with age < 45 years and with ATG+Aza+Pred+CsA immunosuppression regimen. ATN increased the AR incidence and this was associated with a higher ocurrence of CD and a worst graft function at 1 year. The graft lost by CD duplicate in the patients with AR. Graft survival was significantly worse in the patients with AR. The AR did not adversely affect patient survival.
本研究旨在探讨以环孢素A为基础的免疫抑制方案下尸体肾移植急性排斥反应（AR）的发生率及原因，并研究AR对慢性肾功能不全（CD）发生及移植结局的影响。
我们分析了1985年12月至1999年12月间794例尸体供肾移植病例。研究了主要的供体、受体及移植物相关因素及其对移植结局的影响。65%的AR诊断基于临床和实验室检查结果：发热、尿量减少、移植肾区疼痛和/或压痛以及血清肌酐至少升高0.4mg/dl；35%的AR诊断经活检证实。统计分析包括单因素和多因素分析。移植肾和患者生存率采用Kaplan-Meier法计算（并进行对数秩检验）。
在本研究纳入的794例肾移植中，498例（63%）未发生AR，296例（37%）至少发生1次AR。AR的总体发生率为37%，呈下降趋势，在最后两年即1998年和1999年分别降至24%和25%。AR与尸体供体相关因素有关[非创伤性死亡原因（p = 0.018）、用Eurocollins液灌注（p = 0.008）及冷缺血时间>24小时（p = 0.032）]，也与受体相关因素有关[年龄<45岁（p = 0.000）及采用抗胸腺细胞球蛋白（ATG）+硫唑嘌呤（Aza）+泼尼松（Pred）+环孢素A（CsA）的免疫抑制方案（p = 0.006）]。关于移植物相关因素，急性肾小管坏死（ATN）与AR发生率较高有关（无ATN的AR患者中为35%，有ATN的AR患者中为48%，p = 0.008），这导致慢性肾功能不全（CD）显著增加（p = 0.000），且在第1年末移植肾功能更差（p = 0.000）。我们的结果还显示，存在AR时，因CD导致移植肾丢失的比例大幅增加（23%对49%）。发生AR的患者1年、3年、5年及10年和15年移植肾生存率分别为94%、85%、74%、50%和38%，未发生AR的患者分别为97%、91%、87%、77%和67%。这些结果具有统计学意义（p = 0.000）。AR对患者生存率无影响（p = 0.814）。
我们的AR总体发生率（37%）呈下降趋势，去年降至25%。AR发生率在以下情况下显著增加：来自非创伤性死亡原因的尸体供体的移植物、用Eurocollins液保存、冷缺血时间>24小时，以及年龄<45岁且采用ATG + Aza + Pred + CsA免疫抑制方案的受体。ATN增加了AR发生率，这与CD发生率较高及1年时移植肾功能更差有关。发生AR的患者中因CD导致的移植肾丢失翻倍。发生AR的患者移植肾生存率显著更差。AR对患者生存率无不良影响。
