Charité University Medicine Berlin, Campus Virchow Clinic, Department of Nephrology and Internal Intensive Care Medicine, Berlin, Germany.
Department of Internal Medicine II, Martin-Luther-University Halle, Halle, Germany.
Blood Purif. 2018;45(1-3):131-138. doi: 10.1159/000484925. Epub 2017 Dec 22.
Vascular calcification is a common phenomenon in patients with chronic kidney disease and strongly associated with increased cardiovascular mortality. Vascular calcification is an active process mediated in part by inflammatory processes in vascular smooth muscle cells (VSMC). These could be modified by the insufficient removal of proinflammatory cytokines through conventional high-flux (HF) membranes. Recent trials demonstrated a reduction of inflammation in VSMC by use of dialysis membranes with a higher and steeper cut-off. These membranes caused significant albumin loss. Therefore, the effect of high retention Onset (HRO) dialysis membranes on vascular calcification and its implications in vitro was evaluated.
In the PERCI II trial, 48 chronic dialysis patients were dialyzed using HF and HRO dialyzers and serum samples were collected. Calcifying VSMC were incubated with the serum samples. Calcification was determined using alizarin red staining (AZR) and determination of alkaline phosphatase (ALP) activity. Furthermore, apoptosis was evaluated, and release of matrix Gla protein (MGP), osteopontin (OPN) and growth differentiation factor 15 (GDF-15) were measured in cell supernatants.
Vascular calcification in vitro was significantly reduced by 24% (ALP) and 36% (AZR) after 4 weeks of HRO dialysis and by 33% (ALP) and 48% (AZR) after 12 weeks of dialysis using HRO membranes compared to HF dialysis. Apoptosis was significantly lower in the HRO group. The concentrations of MGP and OPN were significantly elevated after incubation with HF serum compared to HRO serum and healthy controls. Similarly, GDF-15 release in the supernatant was elevated after incubation with HF serum, an effect significantly ameliorated after treatment with HRO medium.
Expanded haemodialysis therapy reduces the pro-calcific potential of serum from dialysis patients in vitro. With a markedly reduced albumin filtration compared to high cut-off dialysis, use of the HRO dialyzers may possibly provide a treatment option for chronic dialysis patients to reduce the progression of vascular calcification.
血管钙化是慢性肾脏病患者的常见现象，与心血管死亡率的增加密切相关。血管钙化是血管平滑肌细胞（VSMC）中部分炎症过程介导的活跃过程。这些过程可以通过传统高通量（HF）膜对促炎细胞因子的清除不足来改变。最近的试验表明，使用更高和更陡峭截止值的透析膜可减少 VSMC 中的炎症。这些膜会导致显著的白蛋白丢失。因此，评估高通量保留起始（HRO）透析膜对血管钙化的影响及其在体外的意义。
在 PERCI II 试验中，48 名慢性透析患者使用 HF 和 HRO 透析器进行透析，并收集血清样本。用血清样本孵育钙化的 VSMC。通过茜素红染色（AZR）和碱性磷酸酶（ALP）活性测定来确定钙化。此外，还评估了细胞凋亡，并测量细胞上清液中基质 Gla 蛋白（MGP）、骨桥蛋白（OPN）和生长分化因子 15（GDF-15）的释放。
与 HF 透析相比，HRO 透析 4 周后血管钙化分别减少 24%（ALP）和 36%（AZR），12 周后分别减少 33%（ALP）和 48%（AZR）。HRO 组的细胞凋亡明显较低。与 HRO 血清和健康对照组相比，HF 血清孵育后 MGP 和 OPN 的浓度明显升高。同样，HF 血清孵育后上清液中 GDF-15 的释放增加，而用 HRO 培养基处理后，这种作用明显改善。
扩展血液透析治疗可降低体外透析患者血清的促钙化潜能。与高通量透析相比，HRO 透析器的使用白蛋白滤过率显著降低，可能为慢性透析患者提供一种治疗选择，以减少血管钙化的进展。
