Nephrology Dialysis and Transplantation Department, Amiens University Hospital, 80054 Amiens, France.
Nephrology Section, Department of Internal Medicine and Pediatrics, Ghent University Hospital, Corneel Heymanslaan 10, 9000 Ghent, Belgium.
Int J Mol Sci. 2021 Sep 29;22(19):10549. doi: 10.3390/ijms221910549.
Chronic kidney disease (CKD) is a major cause of death worldwide and is associated with a high risk for cardiovascular and all-cause mortality. In CKD, endothelial dysfunction occurs and uremic toxins accumulate in the blood. miR-126 is a regulator of endothelial dysfunction and its blood level is decreased in CKD patients. In order to obtain a better understanding of the physiopathology of the disease, we correlated the levels of miR-126 with several markers of endothelial dysfunction, as well as the representative uremic toxins, in a large cohort of CKD patients at all stages of the disease. Using a univariate analysis, we found a correlation between eGFR and most markers of endothelial dysfunction markers evaluated in this study. An association of miR-126 with all the evaluated uremic toxins was also found, while uremic toxins were not associated with the internal control, specifically . The correlation between the expression of endothelial dysfunction biomarker Syndecan-1, free indoxyl sulfate, and total p-cresyl glucuronide on one side, and miR-126 on the other side was confirmed using multivariate analysis. As CKD is associated with reduced endothelial glycocalyx (eGC), our results justify further evaluation of the role of correlated parameters in the pathophysiology of CKD.
慢性肾脏病(CKD)是全球范围内主要的死亡原因之一,与心血管疾病和全因死亡率的高风险相关。在 CKD 中,内皮功能障碍发生,尿毒症毒素在血液中积累。miR-126 是内皮功能障碍的调节剂,其在 CKD 患者中的血液水平降低。为了更好地了解疾病的病理生理学,我们将 miR-126 水平与疾病各个阶段的大量 CKD 患者的几种内皮功能障碍标志物以及代表性尿毒症毒素进行了相关性分析。使用单变量分析,我们发现 eGFR 与本研究中评估的大多数内皮功能障碍标志物之间存在相关性。miR-126 与所有评估的尿毒症毒素也存在关联,而尿毒症毒素与内部对照物(具体为.)没有关联。使用多变量分析证实了内皮功能障碍生物标志物 Syndecan-1、游离吲哚硫酸和总对甲酚葡糖苷酸与 miR-126 之间的表达的相关性。由于 CKD 与内皮糖萼(eGC)减少相关,我们的结果证明了进一步评估相关参数在 CKD 病理生理学中的作用的合理性。