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载有维生素 E 的膜式透析器可减轻血液透析所致炎症反应。

Vitamin e-loaded membrane dialyzers reduce hemodialysis inflammaging.

机构信息

Unit of Nephrology and Dialysis, Transplantation; Fondazione IRCCS Policlinico «San Matteo», Viale Camillo Golgi 19, 27100, Pavia, Italy.

UOC di Nefrologia e Dialisi, Trapianto, Fondazione IRCCS Policlinico «San Matteo», Viale Camillo Golgi, 19, 27100, Pavia, Italy.

出版信息

BMC Nephrol. 2019 Nov 15;20(1):412. doi: 10.1186/s12882-019-1585-6.

Abstract

BACKGROUND

Inflammaging is a persistent, low-grade, sterile, nonresolving inflammatory state, associated with the senescence of the immune system. Such condition downregulates both innate and adaptive immune responses during chronic disorders as type II diabetes, cancer and hemodialysis, accounting for their susceptibility to infections, malignancy and resistance to vaccination. Aim of this study was to investigate hemodialysis inflammaging, by evaluating changes of several hemodialysis treatments on indoleamine 2,3-dioxygenase-1 activity and nitric oxide formation.

METHODS

We conducted a randomized controlled observational crossover trial. Eighteen hemodialysis patients were treated with 3 different hemodialysis procedures respectively: 1) Low-flux bicarbonate hemodialysis, 2) Low-flux bicarbonate hemodialysis with vitamin E - loaded dialyzers, and 3) Hemodialfitration. The control group consisted of 14 hospital staff healthy volunteers. Blood samples were collected from all 18 hemodialysis patients just after the long interdialytic interval, at the end of each hemodialysis treatment period.

RESULTS

Hemodialysis kynurenine and kynurenine/L - tryptophan blood ratio levels were significantly higher, when compared to the control group, indicating an increased indoleamine 2,3-dioxygenase-1 activity in hemodialysis patients. At the end of the low-flux bicarbonate hemodialysis with vitamin E - loaded dialyzers period, L - tryptophan serum levels remained unchanged vs both low-flux bicarbonate hemodialysis and hemodialfitration. Kynurenine levels instead decreased, resulting in a significant reduction of kynurenine/L - tryptophan blood ratio and indoleamine 2,3-dioxygenase-1 activity, when matched to both low-flux bicarbonate hemodialysis and HDF respectively. Serum nitric oxide control group levels, were significantly lower when compared to all hemodialysis patient groups. Interestingly, low-flux bicarbonate hemodialysis with vitamin E - loaded dialyzers nitric oxide serum levels from venous line blood samples taken 60 min after starting the hemodialysis session were significantly lower vs serum taken simultaneously from the arterial blood line.

CONCLUSIONS

The treatment with more biocompatible hemodialysis procedure as low-flux bicarbonate hemodialysis with vitamin E - loaded dialyzers, reduced indoleamine 2,3-dioxygenase-1 activity and nitric oxide formation when compared to both low-flux bicarbonate hemodialysis and hemodialfitration. These data suggest that low-flux bicarbonate hemodialysis with vitamin E - loaded dialyzers lowering hemodialysis inflammaging, could be associated to changes of proinflammatory signalling a regulated molecular level.

TRIAL REGISTRATION

NCT Number: NCT02981992; Other Study ID Numbers: 20100014090. First submitted: November 26, 2016. First posted: December 5, 2016. Last Update Posted: December 5, 2016.

摘要

背景

炎症衰老(Inflammaging)是一种持续的、低度的、无菌的、未解决的炎症状态,与免疫系统衰老有关。在 2 型糖尿病、癌症和血液透析等慢性疾病中,这种情况会下调先天和适应性免疫反应,导致它们易感染、恶性肿瘤和对疫苗的抵抗力下降。本研究旨在通过评估几种血液透析治疗对吲哚胺 2,3-双加氧酶-1 活性和一氧化氮形成的影响,来研究血液透析炎症衰老。

方法

我们进行了一项随机对照观察性交叉试验。18 名血液透析患者分别接受 3 种不同的血液透析程序:1)低通量碳酸氢盐血液透析,2)载有维生素 E 的低通量碳酸氢盐血液透析,和 3)血液透析滤过。对照组由 14 名医院工作人员健康志愿者组成。所有 18 名血液透析患者在长透析间期后、每次血液透析治疗结束时采集血液样本。

结果

与对照组相比,血液透析犬尿氨酸和犬尿氨酸/L-色氨酸血液比值明显升高,表明血液透析患者吲哚胺 2,3-双加氧酶-1 活性增加。在载有维生素 E 的低通量碳酸氢盐血液透析结束时,L-色氨酸血清水平与低通量碳酸氢盐血液透析和血液透析滤过相比保持不变。然而,犬尿氨酸水平下降,导致犬尿氨酸/L-色氨酸血液比值和吲哚胺 2,3-双加氧酶-1 活性显著降低,与低通量碳酸氢盐血液透析和 HDF 分别匹配。对照组的血清一氧化氮水平明显低于所有血液透析患者组。有趣的是,从血液透析开始后 60 分钟从静脉线采集的载有维生素 E 的低通量碳酸氢盐血液透析的血清一氧化氮水平明显低于从动脉线同时采集的血清。

结论

与低通量碳酸氢盐血液透析和血液透析滤过相比,使用更具生物相容性的血液透析程序,如载有维生素 E 的低通量碳酸氢盐血液透析,可以降低吲哚胺 2,3-双加氧酶-1 活性和一氧化氮的形成。这些数据表明,载有维生素 E 的低通量碳酸氢盐血液透析降低血液透析炎症衰老可能与调节分子水平的促炎信号改变有关。

试验注册

NCT02981992;其他研究 ID 号:20100014090。首次提交:2016 年 11 月 26 日。首次发布:2016 年 12 月 5 日。最后更新发布:2016 年 12 月 5 日。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2f90/6858730/36b5448d78e1/12882_2019_1585_Fig1_HTML.jpg

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