移植后低补体血症：肾移植受者心血管风险的新标志物？

Post-transplant hypocomplementemia: A novel marker of cardiovascular risk in kidney transplant recipients?

机构信息

Unit of Infectious Diseases, Hospital Universitario "12 de Octubre", Instituto de Investigación Hospital "12 de Octubre" (i+12), School of Medicine, Universidad Complutense, Madrid, Spain.

出版信息

Atherosclerosis. 2018 Feb;269:204-210. doi: 10.1016/j.atherosclerosis.2018.01.021. Epub 2018 Jan 27.

DOI:10.1016/j.atherosclerosis.2018.01.021

PMID:29407595

Abstract

BACKGROUND AND AIMS

Cardiovascular disease (CVD) is a leading cause of mortality after kidney transplantation (KT). The potential role of the complement system in the pathogenesis of post-transplant CVD remains unexplored.

METHODS

Serum complement (C3 and C4) levels were measured at baseline and post-transplant months 1 and 6 in 447 kT recipients. The study outcome was post-transplant atherothrombotic event (PAE), a composite of acute coronary syndrome, critical peripheral arterial disease, stroke and/or transient ischemic attack.

RESULTS

After a median follow-up of 4.2 years, 48 PAEs occurred in 43 patients (cumulative incidence: 9.6%; incidence rate: 2.6 events per 100 transplant-years). No differences were found in C3 and C4 levels at baseline or month 1 between patients with or without PAE. However, C3 levels at month 6 were significantly lower in patients developing PAE beyond that point (i.e., late PAE) (96.9 ± 22.3 vs. 109.6 ± 24.0 mg/dL; p = 0.013). The presence of C3 hypocomplementemia at month 6 was associated with a lower PAE-free survival (p = 0.002). After adjusting for conventional CVD risk factors and acute graft rejection, C3 hypocomplementemia at month 6 remained as an independent risk factor for late PAE in all the exploratory models (minimum hazard ratio: 3.24; p = 0.011). With respect to a model exclusively based on clinical variables, the inclusion of C3 levels at month 6 improved predictive capacity (areas under ROC curves: 0.788 and 0.812, respectively).

CONCLUSIONS

Post-transplant monitoring of serum C3 levels might be useful to identify KT recipients at increased risk of CVD.

摘要

背景与目的

心血管疾病（CVD）是肾移植（KT）后死亡的主要原因。补体系统在移植后 CVD 发病机制中的潜在作用仍未得到探索。

方法

在 447 例 KT 受者中，在基线和移植后 1 个月和 6 个月测量血清补体（C3 和 C4）水平。研究结果是移植后动脉粥样血栓形成事件（PAE），包括急性冠状动脉综合征、严重外周动脉疾病、中风和/或短暂性脑缺血发作的复合事件。

结果

中位随访 4.2 年后，43 例患者发生 48 例 PAE（累积发生率：9.6%；发生率：每 100 个移植年 2.6 例）。PAE 患者和无 PAE 患者在基线或 1 个月时的 C3 和 C4 水平无差异。然而，发生 PAE （即迟发性 PAE）的患者在 6 个月时的 C3 水平显著较低（96.9±22.3 与 109.6±24.0 mg/dL；p=0.013）。6 个月时存在 C3 低补体血症与 PAE 无生存相关（p=0.002）。在调整了传统 CVD 危险因素和急性移植物排斥反应后，6 个月时的 C3 低补体血症在所有探索性模型中仍然是迟发性 PAE 的独立危险因素（最小危险比：3.24；p=0.011）。与仅基于临床变量的模型相比，纳入 6 个月时的 C3 水平提高了预测能力（ROC 曲线下面积：分别为 0.788 和 0.812）。