Supplementary Material for: The Role of Uremic Retention Solutes in the MIA Syndrome in Hemodialysis Subjects

<b><i>Introduction:</i></b> In chronic kidney disease (CKD), the high morbidity and mortality risk for cardiovascular disease (CVD) are not easily explained only on the basis of traditional factors. Among nontraditional ones involved in CKD, malnutrition, inflammation, and atherosclerosis/calcification have been described as the “MIA syndrome.” <b><i>Methods:</i></b> In this pilot study, we evaluated the association between the variation in serum levels of 27 uremic retention solutes plus 6 indexes related to the MIA syndrome processes in a population of dialysis patients. <b><i>Results:</i></b> As expected, we found a direct correlation between serum albumin and both phosphate and total cholesterol (<i>r</i> = 0.54 and 0.37, respectively; <i>p</i> &lt; 0.05). Moreover, total cholesterol and phosphate directly correlate (<i>r</i> = 0.40, <i>p</i> &lt; 0.05). The relationship between malnutrition and inflammation is highlighted by the correlation of serum cholesterol levels with serum alpha-1 acid glycoprotein and IL-6 levels (<i>r</i> = −0.56, <i>r</i> = −0.39, respectively; <i>p</i> &lt; 0.05). Moreover, the relation between inflammation and atherosclerosis/calcification is supported by the correlation of IL-6 with VEGF levels and vascular smooth muscle cell high-Pi in vitro calcification (<i>r</i> = 0.81, <i>r</i> = 0.66, respectively; <i>p</i> &lt; 0.01). <b><i>Conclusion:</i></b> We found significant correlations between several uremic retention solutes and malnutrition, inflammation, and atherosclerosis/calcification. Our findings support the hypothesis of a central role of the <i>uremic milieu</i> in the MIA syndrome and ultimately in the pathogenesis of CKD-specific CVD risk factors.

引言：慢性肾脏病（chronic kidney disease, CKD）患者罹患心血管疾病（cardiovascular disease, CVD）的高发病率与死亡率风险，难以仅通过传统危险因素加以阐释。在慢性肾脏病相关的非传统危险因素中，营养不良、炎症及动脉粥样硬化/钙化被统称为“MIA综合征”。
方法：本先导性研究针对透析患者群体，探讨了27种尿毒症潴留溶质的血清水平变化，以及6项与MIA综合征病理过程相关的指标之间的关联。
结果：正如预期，我们观察到血清白蛋白与磷酸盐、总胆固醇均呈显著正相关（相关系数r分别为0.54和0.37，p<0.05）。此外，总胆固醇与磷酸盐亦呈正相关（r=0.40，p<0.05）。血清胆固醇水平与血清α₁-酸性糖蛋白、IL-6水平的负相关（r分别为-0.56和-0.39，p<0.05），凸显了营养不良与炎症之间的内在关联。进一步而言，IL-6与血管内皮生长因子（vascular endothelial growth factor, VEGF）水平、血管平滑肌细胞高磷体外钙化的相关性（r分别为0.81和0.66，p<0.01），证实了炎症与动脉粥样硬化/钙化之间的联系。
结论：本研究发现多种尿毒症潴留溶质与营养不良、炎症及动脉粥样硬化/钙化之间存在显著相关性。研究结果支持“尿毒症微环境（uremic milieu）在MIA综合征中发挥核心作用，并最终参与慢性肾脏病特异性心血管疾病危险因素的发病机制”这一假说。