Klimontov Vadim V, Korbut Anton I, Orlov Nikolai B, Dashkin Maksim V, Konenkov Vladimir I
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.
J Clin Med. 2020 Sep 18;9(9):3006. doi: 10.3390/jcm9093006.
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.
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。
