Antonelou Marianna H, Georgatzakou Hara T, Tzounakas Vasillis L, Velentzas Athanassios D, Kokkalis Apostolos C, Kriebardis Anastasios G, Papassideri Issidora S
Department of Cell Biology and Biophysics, Faculty of Biology, NKUA, Greece.
Chronic Hemodialysis Centre "Ionion", Piraeus, Greece.
J Proteomics. 2014 Apr 14;101:88-101. doi: 10.1016/j.jprot.2014.02.009. Epub 2014 Feb 15.
Chronic kidney disease is a risk factor for cardiovascular mortality. This study uncovers pieces of hematological and erythrocyte protein variability observed in end stage renal disease (ESRD) in relation to disease progression/duration and mortality. Using a variety of experimental approaches, erythropoietin/dialysis-treated patients were compared to healthy individuals and had been followed for 36months. During that period, half of the patients died from cardiovascular diseases. The high levels of uremic toxins in those patients were associated with damaged erythrocytes, bad tolerance and poor response to hemodialysis therapy. The postmortem study revealed significant variation in alkaline phosphatase, duration of dialysis, erythrocyte transformation and intracellular hemoglobin concentration compared to the survived patients. The erythrocyte proteins showed substantial remodeling characteristic of pathologic regulation of cell hydration and susceptibility to the dialysis-induced oxidation defects. According to the follow-up study, duration of hemodialysis was associated with a trend towards increased intracellular hemoglobin concentration, membrane expression of glucose transporter-1 and stomatin as well as lower levels of circulating stomatocytes. The uremic index variation in long survived patients is accurately reflected in plasma and erythrocyte oxidative stress modifications. The ESRD patients exhibit impressive compensatory responses to the chronic challenges of the uremic milieu.
This study demonstrates novel blood modifications probably associated with the duration of erythropoietin/hemodialysis treatment, disease progression and cardiovascular mortality in end stage renal disease. The observed variability adds new pieces to the erythrocyte pathophysiology puzzle in end stage renal disease and suggests novel hematologic and proteomic factors for consideration in future large scale studies on cardiovascular morbidity and mortality candidate biomarkers in uremic patients.
慢性肾脏病是心血管疾病死亡的一个危险因素。本研究揭示了在终末期肾病（ESRD）中观察到的血液学和红细胞蛋白变异性与疾病进展/病程及死亡率的关系。使用多种实验方法，将接受促红细胞生成素/透析治疗的患者与健康个体进行比较，并随访36个月。在此期间，一半的患者死于心血管疾病。这些患者体内高水平的尿毒症毒素与红细胞受损、耐受性差及对血液透析治疗反应不佳有关。尸检研究显示，与存活患者相比，碱性磷酸酶、透析时长、红细胞转化及细胞内血红蛋白浓度存在显著差异。红细胞蛋白显示出细胞水合病理调节及对透析诱导氧化缺陷易感性的显著重塑特征。根据随访研究，血液透析时长与细胞内血红蛋白浓度升高、葡萄糖转运蛋白-1和 stomatin 的膜表达增加以及循环中口形红细胞水平降低的趋势相关。长期存活患者的尿毒症指数变化准确反映在血浆和红细胞氧化应激改变中。ESRD 患者对尿毒症环境的慢性挑战表现出令人印象深刻的代偿反应。
本研究证明了可能与促红细胞生成素/血液透析治疗时长、疾病进展及终末期肾病心血管死亡率相关的新型血液改变。观察到的变异性为终末期肾病红细胞病理生理学难题增添了新内容，并提示了新的血液学和蛋白质组学因素，以供未来关于尿毒症患者心血管发病率和死亡率候选生物标志物的大规模研究参考。
