Department of Internal Medicine, Division of Nephrology, Erciyes University School of Medicine, Kayseri, Turkey.
Division of Renal Medicine and Baxter Novum, Karolinska Institutet, Stockholm, Sweden.
Eur J Clin Invest. 2020 Dec;50(12):e13350. doi: 10.1111/eci.13350. Epub 2020 Jul 31.
Neointimal hyperplasia is the main cause of arteriovenous fistula (AVF) failure. Hypoxia-inducible factors (HIFs) factors are associated with neointimal hyperplasia. Thus, we investigated the association between HIF-2 alpha (HIF-2α) and AVF maturation in end-stage kidney disease (ESKD) patients.
This prospective cohort study was conducted in 21 voluntary healthy subjects and 50 patients with ESKD who were eligible for AVF creation. Inclusion criteria were being ESKD patients without a history of AVF surgery and dialysis. Eight patients excluded from the study due to having unavailable veins six patients were excluded due to acute thrombosis after surgery. One patient lost to follow-up. A total of 35 patients were included in final analysis. The blood samples were collected a day before the AVF surgery for biochemical parameters and HIF-2α measurement. HIF-2α levels were measured by the ELISA method.
Compared with healthy subjects, ESKD patients had a significantly higher level of HIF-2α. [1.3 (1.0-1.9) vs 2.2 (1.6-3.0)] (P = .002). Patients were divided into two groups after the evaluation of AVF maturation, as the mature group (n = 19) and the failure group (n = 16). Serum HIF-2α level was 1.7 (1.1-1.8) in the mature group; however, it was 3.1 (2.8-3.3 in failure group (P < .001). Multiple logistic regression analyses showed that HIF-2α independently predicted AVF maturation. The ROC curve analysis showed that HIF-2α > 2.65 predicted AVF maturation failure with the 87% sensitivity and 94% specificity [AUC:0.947, 95% CI (0.815-0.994), P < .001].
HIF-2-α levels were higher in ESKD patients than healthy subjects. HIF-2-α could be a marker of AVF maturation failure.
内膜增生是动静脉瘘（AVF）失功的主要原因。缺氧诱导因子（HIFs）与内膜增生有关。因此，我们研究了低氧诱导因子-2α（HIF-2α）与终末期肾病（ESKD）患者 AVF 成熟之间的关系。
这是一项前瞻性队列研究，纳入了 21 名自愿健康受试者和 50 名有 AVF 造瘘术适应证的 ESKD 患者。纳入标准为 ESKD 患者且无 AVF 手术史和透析史。由于静脉不可用，8 名患者被排除在研究之外；6 名患者由于术后急性血栓形成被排除；1 名患者失访。最终共有 35 名患者纳入最终分析。AVF 手术前一天采集血液样本，用于生化参数和 HIF-2α 测量。采用 ELISA 法测量 HIF-2α 水平。
与健康受试者相比，ESKD 患者的 HIF-2α 水平明显升高[1.3（1.0-1.9）比 2.2（1.6-3.0）]（P =.002）。根据 AVF 成熟情况对患者进行评估后，将其分为成熟组（n=19）和失败组（n=16）。成熟组血清 HIF-2α 水平为 1.7（1.1-1.8），而失败组为 3.1（2.8-3.3）（P<.001）。多因素 logistic 回归分析显示，HIF-2α 独立预测 AVF 成熟。ROC 曲线分析显示，HIF-2α>2.65 预测 AVF 成熟失败的敏感性为 87%，特异性为 94%[AUC：0.947，95%CI（0.815-0.994），P<.001]。
ESKD 患者的 HIF-2α 水平高于健康受试者。HIF-2α 可能是 AVF 成熟失败的标志物。
