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不对称二甲基精氨酸和血管生成素样蛋白 2 是透析前非糖尿病慢性肾脏病患者心血管风险的独立预测因子。

Asymmetric dimethylarginine and angiopoietin-like protein-2 are independent predictors of cardiovascular risk in pre-dialysis non-diabetic chronic kidney disease patients.

机构信息

Department of Biochemistry, Jawaharlal Institute of Postgraduate Medical Education and Research, Dhanvantari Nagar, Puducherry, 605006, India.

Department of Nephrology, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry, India.

出版信息

Int Urol Nephrol. 2020 Jul;52(7):1321-1328. doi: 10.1007/s11255-020-02484-0. Epub 2020 May 14.

Abstract

BACKGROUND

Chronic kidney disease (CKD) is associated with increased cardiovascular (CVD) morbidity and mortality. Hence, this study was carried out to assess the biomarkers of endothelial dysfunction and inflammation as predictors of CVD risk in Indian patients with CKD.

METHODS

In this case control study, we recruited 43 patients with CKD and 43 healthy control volunteers. Circulating levels of endothelial dysfunction markers [asymmetric dimethylarginine (ADMA), angiopoietin-like protein-2 (ANGPTL2), matrix metallopeptidase 9 (MMP-9)] and systemic inflammation [high-sensitivity C-reactive protein (hs-CRP)] were assessed in the study population. All study participants underwent brachial artery flow mediated dilation (FMD) to estimate endothelial dysfunction. Disease severity (e-GFR) was assessed by a nephrologist.

RESULTS

CKD patients showed markedly elevated levels of ADMA, ANGPTL2, MMP-9, and hs-CRP. FMD and eGFR were significantly decreased in cases, as compared to the controls. ADMA, ANGPTL2, MMP-9 and hs-CRP showed significant positive correlation with one another and significant negative correlation with FMD and disease severity. We also observed a significant negative correlation of FMD with disease severity and duration of CKD. In the multiple linear regression model, ADMA and ANGPTL2 were found to be independent predictors of FMD.

CONCLUSION

In CKD patients, there is significantly increased endothelial dysfunction and systemic inflammation, which showed a positive correlation with disease severity. Thus, the markers of endothelial dysfunction such as ADMA and ANGPTL2 can be used as predictors of CVD risk in CKD.

摘要

背景

慢性肾脏病(CKD)与心血管疾病(CVD)发病率和死亡率增加有关。因此,本研究旨在评估内皮功能障碍和炎症的生物标志物是否可作为印度 CKD 患者 CVD 风险的预测因子。

方法

在这项病例对照研究中,我们招募了 43 名 CKD 患者和 43 名健康对照志愿者。评估了研究人群中内皮功能障碍标志物(不对称二甲基精氨酸(ADMA)、血管生成素样蛋白 2(ANGPTL2)、基质金属蛋白酶 9(MMP-9))和全身炎症(高敏 C 反应蛋白(hs-CRP))的循环水平。所有研究参与者均接受肱动脉血流介导的扩张(FMD)以评估内皮功能障碍。肾脏病医生评估疾病严重程度(e-GFR)。

结果

CKD 患者的 ADMA、ANGPTL2、MMP-9 和 hs-CRP 水平显著升高。与对照组相比,病例组的 FMD 和 eGFR 明显降低。ADMA、ANGPTL2、MMP-9 和 hs-CRP 彼此之间呈显著正相关,与 FMD 和疾病严重程度呈显著负相关。我们还观察到 FMD 与疾病严重程度和 CKD 病程呈显著负相关。在多元线性回归模型中,ADMA 和 ANGPTL2 被发现是 FMD 的独立预测因子。

结论

在 CKD 患者中,内皮功能障碍和全身炎症显著增加,且与疾病严重程度呈正相关。因此,ADMA 和 ANGPTL2 等内皮功能障碍标志物可作为 CKD 患者 CVD 风险的预测因子。

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