Donor catecholamine use reduces acute allograft rejection and improves graft survival after cadaveric renal transplantation
Donor catecholamine use reduces acute allograft rejection and improves graft survival after cadaveric renal transplantation
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DOI：
10.1046/j.1523-1755.1999.00567.x
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发表时间：
1999-08-01
影响因子：
19.6
通讯作者：
van der Woude, FJ
中科院分区：
文献类型：
--
作者：
Schnuelle, P;Lorenz, D;van der Woude, FJ
流行病学数据表明，尽管人类淋巴细胞抗原（HLA）错配程度较高，但来自非亲属活体供者的肾移植比尸体移植的存活率更高。我们进行了一项以中心为基础的病例对照研究，以确定影响尸体移植早期结果的供体特异性决定因素。研究数据库包括1989年6月至1998年9月间在本中心进行的152例连续尸体肾移植。其中，24名患者接受了再次移植。根据器官共享的欧洲移植规则，在预期HLA匹配的基础上分配供肾。免疫抑制治疗包括以环孢素为基础的三联用药方案。在67例受者中，在移植后的第一个月内至少发生一次急性排斥反应。他们作为病例，其余85名患者作为对照。对标准化的神经移植坏死肾报告中获得的供者特异性解释变量进行逐步逻辑回归。在二次评估中，采用Cox回归模型进一步测量长期随访对移植物存活的影响。所有移植受者的平均随访时间为3.8年（SD 2.7年）。供体年龄[优势比（OR） 1.05；（95% CI， 1.02至1.08），脑外伤作为死亡原因（OR 2.75, 95% CI， 1.16至6.52），以及HLA-DR不匹配（OR 3.0, 95% CI， 1.47至6.12）与急性排斥反应风险增加相关，而供体使用多巴胺（OR 0.22, 95% CI， 0.09至0.51）和/或去甲肾上腺素（OR 0.24, 95% CI， 0.10至0.60）分别导致显著的有益效果。在多变量Cox回归分析中，在长期随访中，供体治疗多巴胺（HR 0.44, 95% CI 0.22 ~ 0.84）和去甲肾上腺素（HR 0.30, 95% CI 0.10 ~ 0.87）仍然是更好的移植物存活的重要预测因素。我们的数据强烈表明，在重症监护期间使用儿茶酚胺对死后器官供体有免疫调节作用，并在长期随访中提高移植物存活率。这些发现至少可以部分解释为肾上腺素能物质对移植物血管壁粘附分子（VCAM， e -选择素）表达的下调作用。
Background Epidemiological data implicate that renal transplants from living unrelated donors result in superior survival rates as compared with cadaveric grafts, despite a higher degree of human lymphocyte antigen (HLA) mismatching. We undertook a center-based case control study to identify donor-specific determinants affecting early outcome in cadaveric transplantation.Methods. The study database consisted of 152 consecutive cadaveric renal transplants performed at our center between June 1989 and September 1998. Of these, 24 patients received a retransplant. Donor kidneys were allocated on the basis of prospective HLA matching according to the Eurotransplant rules of organ sharing. Immunosuppressive therapy consisted of a cyclosporine-based triple-drug regimen. In 67 recipients, at least one acute rejection episode occurred during the first month after transplantation. They were taken as cases, and the remaining 85 patients were the controls. Stepwise logistic regression was done on donor-specific explanatory variables obtained from standardized Eurotransplant Necrokidney reports. In a secondary evaluation, the impact on graft survival in long-term follow-up was further measured by applying a Cox regression model. The mean follow-up of all transplant recipients was 3.8 years (SD 2.7 years).Results. Donor age [odds ratio (OR) 1.05; 95% CI, 1.02 to 1.08], traumatic brain injury as cause of death (OR 2.75; 95% CI, 1.16 to 6.52), and mismatch on HLA-DR (OR 3.0; 95% CI, 1.47 to 6.12) were associated with an increased risk of acute rejection, whereas donor use of dopamine (OR 0.22; 95% CI, 0.09 to 0.51) and/or noradrenaline (OR 0.24; 95% CI, 0.10 to 0.60) independently resulted in a significant beneficial effect. In the multivariate Cox regression analysis, both donor treatment with dopamine (HR 0.44; 95% CI, 0.22 to 0.84) and noradrenaline (HR 0.30; 95% CI, 0.10 to 0.87) remained a significant predictor of superior graft survival in long-term follow-up.Conclusions. Our data strongly suggest that the use of catecholamines in postmortal organ donors during intensive care results in immunomodulating effects and improves graft survival in long-term follow-up. These findings may at least partially be explained by down-regulating effects of adrenergic substances on the expression of adhesion molecules (VCAM, E-selectin) in the vessel walls of the graft.