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白蛋白尿性和非白蛋白尿性糖尿病肾病患者循环细胞因子和生长因子的多重微珠阵列分析

Multiplex Bead Array Assay of a Panel of Circulating Cytokines and Growth Factors in Patients with Albuminuric and Non-AlbuminuricDiabetic Kidney Disease.

作者信息

Klimontov Vadim V, Korbut Anton I, Orlov Nikolai B, Dashkin Maksim V, Konenkov Vladimir I

机构信息

Research Institute of Clinical and Experimental Lymphology-Branch of the Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences, 630060 Novosibirsk, Russia.

出版信息

J Clin Med. 2020 Sep 18;9(9):3006. doi: 10.3390/jcm9093006.

Abstract

A panel of cytokines and growth factors, mediating low-grade inflammation and fibrosis, was assessed in patients with type 2 diabetes (T2D) and different patterns of chronic kidney disease (CKD). Patients with long-term T2D (N = 130) were classified into four groups: no signs of CKD; estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m without albuminuria; albuminuria and eGFR ≥60 mL/min/1.73 m; albuminuria and eGFR <60 mL/min/1.73 m. Thirty healthy subjects were acted as control. Twenty-seven cytokines and growth factors were assessed in serum by multiplex bead array assay. Serum hs-CRP, urinary nephrin, podocine, and WFDC2 were measured by ELISA. Patients with T2D showed elevated IL-1Ra, IL-6, IL-17A, G-CSF, IP-10, MIP-1α, and bFGF levels; concentrations of IL-4, IL-12, IL-15, INF-γ, and VEGF were decreased. IL-6, IL-17A, G-CSF, MIP-1α, and bFGF correlated negatively with eGFR; IL-10 and VEGF demonstrated negative associations with WFDC2; no relationships with podocyte markers were found. Adjusted IL-17A and MIP-1α were predictors of non-albuminuric CKD, IL-13 predicted albuminuria with preserved renal function, meanwhile, IL-6 and hsCRP were predictors of albuminuria with eGFR decline. Therefore, albuminuric and non-albuminuric CKD in T2D patients are associated with different pro-inflammatory shifts in the panel of circulating cytokines.

摘要

在2型糖尿病(T2D)患者以及不同类型的慢性肾脏病(CKD)患者中,对一组介导低度炎症和纤维化的细胞因子及生长因子进行了评估。患有长期T2D的患者(N = 130)被分为四组:无CKD迹象;估算肾小球滤过率(eGFR)<60 mL/(min·1.73 m²)且无蛋白尿;有蛋白尿且eGFR≥60 mL/(min·1.73 m²);有蛋白尿且eGFR<60 mL/(min·1.73 m²)。30名健康受试者作为对照。通过多重微珠阵列分析法评估血清中的27种细胞因子和生长因子。通过ELISA法检测血清高敏C反应蛋白(hs-CRP)、尿nephrin、podocine和WFDC2。T2D患者的白细胞介素-1受体拮抗剂(IL-1Ra)、白细胞介素-6(IL-6)、白细胞介素-17A(IL-17A)、粒细胞集落刺激因子(G-CSF)、干扰素诱导蛋白10(IP-10)、巨噬细胞炎性蛋白-1α(MIP-1α)和碱性成纤维细胞生长因子(bFGF)水平升高;白细胞介素-4(IL-4)、白细胞介素-12(IL-12)、白细胞介素-15(IL-15)、干扰素-γ(INF-γ)和血管内皮生长因子(VEGF)浓度降低。IL-6、IL-17A、G-CSF、MIP-1α和bFGF与eGFR呈负相关;IL-10和VEGF与WFDC2呈负相关;未发现与足细胞标志物有关联。校正后的IL-17A和MIP-1α是非蛋白尿性CKD的预测指标,IL-13预测肾功能正常时的蛋白尿,同时,IL-6和hsCRP是eGFR下降时蛋白尿的预测指标。因此,T2D患者的蛋白尿性和非蛋白尿性CKD与循环细胞因子组中不同的促炎变化相关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5d1f/7565054/9402b66bbf78/jcm-09-03006-g001.jpg

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