TITLE: The Role of Oxidative Stress Markers in Predicting Acute Thrombotic Occlusion of Haemodialysis Vascular Access and Progressive Stenotic Dysfunction Demanding Angioplasty.
ABSTRACT: Haemodialysis vascular access (VA) dysfunction is a major cause of morbidity in haemodialysis (HD) patients. Primary venous outflow occlusion and restenosis after percutaneous transluminal angioplasty (PTA) are two major obstacles for the long-term use of dialysis VA. It remains unclear whether oxidative stress markers can be used as predictors for thrombotic occlusion of VA and progressive stenosis dysfunction demanding PTA. All routine HD patients at one teaching hospital participated in this study including ankle-brachial index (ABI) examinations and serum oxidative stress markers. The serum oxidative stress markers (high-sensitivity C-reactive protein (hs-CRP), matrix metalloproteinase-2 (MMP-2), MMP-9, homocysteine, asymmetrical dimethylarginine (ADMA), nitrate oxidase (NO), tumour necrosis factor-α (TNF-α), monocyte chemotactic protein 1 (MCP-1), interleukin-1β (IL-1β), and transforming growth factor-β (TGF-β)) were measured using immunosorbent assays in 159 HD patients (83 men and 76 women; mean age: 65 ± 12 years). The participants met the following criteria: (1) received regular HD treatment for at least 6 months, without clinical evidence of acute or chronic inflammation, recent myocardial infarction, unstable angina or circulatory congestion; and (2) received an arteriovenous fistula (AVF)/arteriovenous graft (AVG: polytetrafluoroethylene, PTFE) as the current VA for more than 6 months, without interventions within the last 6 months. All the participants were followed up clinically for up to 12 months to estimate the amount of primary thrombotic occlusion and VA dysfunction demanding PTA. During the 12-month observation, 24 patients (15.1%) had primary thrombotic occlusion of VAs. Another 24 patients (15.1%) required PTA because of clinical dysfunction of access. Additionally, during the follow-up period, restenosis occurred in 12 patients (50% of 24 patients). The access types of arteriovenous grafts (AVGs) and a diagnosis of peripheral arterial occlusive disease (PAOD) were two strong predictors for acute thrombotic events of VA (hazard ratio (HR): 16.93 vs. 2.35; p < 0.001 vs. 0.047). Comparing dysfunctional with non-dysfunctional VAs, up to 27.7% of patients with high levels of ADMA (>0.6207 μM, N = 65) received required PTA compared with 4.4% of those with low levels (≤0.6207 μM; N = 90; p < 0.001). In multivariate analysis, the plasma baseline levels of ADMA independently conferred nearly 4.55 times the risk of primary stenotic dysfunction of HD VA (HR: 4.55; 95% confidence interval: 1.20 to 17.26; p = 0.026). In conclusion, our findings suggest the role of ADMA in the development of symptomatic VA dysfunction. Additionally, PAOD severity can be used in clinical practice to predict whether acute thrombotic occlusion of VA will easily occur in HD patients.
SOURCE: Chan JS, Hsiao PJ, Chiang WF, et al. The Role of Oxidative Stress Markers in Predicting Acute Thrombotic Occlusion of Haemodialysis Vascular Access and Progressive Stenotic Dysfunction Demanding Angioplasty[J]. Antioxidants (Basel), 2021,10(4)DOI: 10.3390/antiox10040569.
血液透析血管通路（VA）功能障碍是血液透析（HD）患者发病的主要原因。经皮腔内血管成形术（PTA）后原发性静脉流出道闭塞和再狭窄是长期使用透析VA的两个主要障碍。尚不清楚氧化应激标志物是否可以用作VA的血栓闭塞和需要PTA的进行性狭窄功能障碍的预测指标。一家教学医院的所有常规HD患者都参加了这项研究，包括踝肱指数（ABI）检查和血清氧化应激指标。血清氧化应激标志物（高敏C反应蛋白（hs-CRP），基质金属蛋白酶2（MMP-2），MMP-9，高半胱氨酸，不对称二甲基精氨酸（ADMA），硝酸氧化酶（NO），肿瘤坏死因子-TNF（-），单核细胞趋化蛋白1（MCP-1），白细胞介素-1（IL-1）和转化生长因子-（TGF-））在159例HD患者（83例男性和76例女性）中进行了免疫吸附测定；平均年龄：65岁±12岁）。纳入者符合以下标准：（1）接受了至少6个月的常规HD治疗，没有临床证据显示急性或慢性炎症，最近的心肌梗塞，不稳定的心绞痛或循环系统充血； （2）接受动静脉瘘（AVF）/动静脉移植物（AVG：聚四氟乙烯，PTFE）作为当前VA的时间超过6个月，并且在最近6个月内未进行干预。对所有参与者进行了长达12个月的临床随访，以评估原发性血栓闭塞和要求PTA的VA功能障碍的程度。在12个月的观察中，有24例（15.1％）的VA发生了原发性血栓闭塞。由于血管通路的临床功能障碍，另有24例患者（15.1％）需要PTA。此外，在随访期间，再狭窄发生在12例患者中（24例患者中的50％）。动静脉移植物（AVG）的通路类型和诊断为外周动脉闭塞性疾病（PAOD）是VA急性血栓形成事件的两个重要预测指标（危险比（HR）：16.93 vs. 2.35； p <0.001 vs. 0.047）。将功能障碍与非功能障碍的VA进行比较，高达27.7％的ADMA高水平（> 0.6207 μM，N = 65）患者接受了PTA，而低水平仅为4.4%（0.6207 μM； N = 90； p < 0.001）。在多变量分析中，ADMA的血浆基线水平独立赋予HD VA原发性狭窄功能障碍风险的近4.55倍（HR：4.55； 95％置信区间：1.20至17.26； p = 0.026）。总之，我们的发现提示ADMA在有症状的VA功能障碍发展中的作用。另外，PAOD的严重程度可用于临床实践，以预测在HD患者中是否容易发生VA的急性血栓闭塞。
启发：从检测指标方面去预测内瘘潜在问题，氧化应激标志物提供了一种新的思路，氧化应激是否是独立于血流动力学之外的因素？
