Department of Nephrology and Internal Intensive Care Medicine, Charité-Universitaetsmedizin Berlin, Campus Virchow Clinic, Berlin, Germany.
Department of Internal Medicine II, Martin-Luther-University Halle, Halle, Germany.
Nephrol Dial Transplant. 2016 Oct;31(10):1706-12. doi: 10.1093/ndt/gfw293. Epub 2016 Jul 20.
Vascular calcification is enhanced in chronic dialysis patients, possibly due to the insufficient removal of various intermediate molecular weight uraemic toxins such as interleukins with conventional membranes. In this study, we assessed the modulation of in vitro vascular calcification with the use of high cut-off (HCO) membranes in chronic dialysis patients.
In a PERCI trial, 43 chronic dialysis patients were treated with conventional high-flux and HCO filters for 3 weeks in a randomized order following a 2-period crossover design. After each phase, serum predialysis samples were drawn. Calcifying human coronary vascular smooth muscle cells (VSMCs) were incubated with the patient's serum samples. Calcification was assessed with alkaline phosphatase (ALP) and alizarin red staining. In the clinical trial, HCO dialysis reduced the serum levels of the soluble tumour necrosis factor receptor (sTNFR) 1 and 2, vascular cell adhesion molecule 1 (VCAM-1) and soluble interleukin-2 receptor (sIL2R). We therefore investigated the in vitro effects of these mediators on vascular calcification.
VSMCs incubated with HCO dialysis serum showed a 26% reduction of ALP with HCO serum compared with high-flux serum. Alizarin was 43% lower after incubation with the HCO serum compared with the high-flux serum. While sIL2R and sTNFR 1 and 2 showed no effects on VSMC calcification, VCAM-1 caused a dose-dependent enhancement of calcification.
The use of HCO dialysis membranes in chronic dialysis patients reduces the procalcific effects of serum on VSMC in vitro. The mechanisms of the strong effect of HCO on in vitro calcification are not completely understood. One factor may be lower levels of VCAM-1 in HCO serum samples, since VCAM-1 was able to induce vascular calcification in our experiments. Neither sTNFR 1, sTNFR 2 nor sIL2R enhance vascular calcification in vitro. Regardless of the mechanisms, our results encourage further studies of highly permeable filters in chronic dialysis patients.
慢性透析患者的血管钙化增强，这可能是由于常规膜对各种中等分子量的尿毒症毒素（如白细胞介素）的清除不足所致。在这项研究中，我们评估了使用高通量（HCO）膜对慢性透析患者体外血管钙化的调节作用。
在 PERCI 试验中，43 名慢性透析患者采用常规高通量和 HCO 过滤器，以随机顺序进行 3 周的治疗，采用 2 期交叉设计。每个阶段后，抽取患者透析前的血清样本。将钙化的人冠状动脉血管平滑肌细胞（VSMCs）与患者的血清样本孵育。通过碱性磷酸酶（ALP）和茜素红染色评估钙化。在临床试验中，HCO 透析降低了可溶性肿瘤坏死因子受体（sTNFR）1 和 2、血管细胞黏附分子 1（VCAM-1）和可溶性白细胞介素-2 受体（sIL2R）的血清水平。因此，我们研究了这些介质对血管钙化的体外作用。
与高通透性血清相比，用 HCO 透析血清孵育的 VSMCs 的 ALP 减少了 26%。用 HCO 血清孵育后，茜素红降低了 43%。虽然 sIL2R 和 sTNFR 1 和 2 对 VSMC 钙化没有影响，但 VCAM-1 导致钙化呈剂量依赖性增强。
在慢性透析患者中使用 HCO 透析膜可降低血清对 VSMC 的体外促钙化作用。HCO 对体外钙化的强烈作用的机制尚不完全清楚。一个因素可能是 HCO 血清样本中 VCAM-1 水平较低，因为在我们的实验中，VCAM-1 能够诱导血管钙化。sTNFR 1、sTNFR 2 和 sIL2R 均不能在体外增强血管钙化。无论机制如何，我们的结果都鼓励在慢性透析患者中进一步研究高通透性过滤器。
