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。