Kurashina Tomoyuki, Nagasaka Shoichiro, Watanabe Naoya, Yabe Daisuke, Sugi Noriko, Nin Kazuko, Hosokawa Masaya, Nomura Yoshio, Fukushima Mitsuo, Nakai Yoshikatsu, Nishimura Fusanori, Taniguchi Ataru
Division of Endocrinology and Metabolism, Jichi Medical University.
J Atheroscler Thromb. 2014;21(7):730-8. doi: 10.5551/jat.21055. Epub 2014 Apr 8.
Chronic kidney disease (CKD) is associated with cardiovascular events. Tumor necrosis factor (TNF) and/or its receptors have been postulated to be involved in renal pathophysiology. It is unclear whether an increased TNF system activity is present before the development of apparent CKD.
Four hundred and twenty non-diabetic Japanese subjects with an estimated GFR (eGFR) greater than 60 ml/min/1.73 m(2) were recruited for measurement of the HbA1c, insulin, TNF system activity (TNF-α, soluble TNF receptor 1 (sTNF-R1) and sTNF-R2) levels and various parameters, including the lipid, high-sensitivity C-reactive protein (hsCRP), high-molecular-weight (HMW) adiponectin and leptin levels. The subjects were stratified according to the eGFR: the G1 level (eGFR ≧90 ml/min/1.73 m(2)) and the G2 level (90 ＞eGFR ≧60 ml/min/1.73 m(2)).
Whereas no significant differences were observed in gender, body mass index (BMI), blood pressure, insulin, TNF-α, hsCRP, HMW adiponectin or leptin between the two groups, the values for age, HbA1c, triglycerides, sTNF-R1 and sTNF-R2 were significantly higher in the subjects with a G2 level of eGFR than in those with a G1 level. In contrast, the HDL cholesterol levels were significantly lower in the subjects with a G2 level than in those with a G1 level. Linear negative correlations were also observed between eGFR and age, BMI, HbA1c, triglycerides, sTNF-R1 and sTNFR2, respectively. A multiple logistic regression analysis revealed that only sTNF-R2 was associated with the presence of a G2 level of eGFR (Odds ratio 1.092, 95% CI 1.013-1.177, P=0.021).
The circulating sTNF-R2 level is closely associated with the kidney function in non-diabetic Japanese subjects.
慢性肾脏病（CKD）与心血管事件相关。肿瘤坏死因子（TNF）和/或其受体被认为参与肾脏病理生理过程。目前尚不清楚在明显的CKD发生之前，TNF系统活性是否升高。
招募420名估计肾小球滤过率（eGFR）大于60 ml/min/1.73 m²的非糖尿病日本受试者，测量糖化血红蛋白（HbA1c）、胰岛素、TNF系统活性（TNF-α、可溶性TNF受体1（sTNF-R1）和sTNF-R2）水平以及各种参数，包括血脂、高敏C反应蛋白（hsCRP）、高分子量（HMW）脂联素和瘦素水平。根据eGFR将受试者分层：G1水平（eGFR≧90 ml/min/1.73 m²）和G2水平（90＞eGFR≧60 ml/min/1.73 m²）。
两组之间在性别、体重指数（BMI）、血压、胰岛素、TNF-α、hsCRP、HMW脂联素或瘦素方面未观察到显著差异，但G2水平eGFR的受试者在年龄、HbA1c、甘油三酯、sTNF-R1和sTNF-R2的值显著高于G1水平的受试者。相反，G2水平的受试者高密度脂蛋白胆固醇水平显著低于G1水平的受试者。eGFR与年龄、BMI、HbA1c、甘油三酯、sTNF-R1和sTNFR2之间也分别观察到线性负相关。多元逻辑回归分析显示，只有sTNF-R2与G2水平的eGFR存在相关（比值比1.092，95%可信区间1.013 - 1.177，P = 0.021）。
在非糖尿病日本受试者中，循环sTNF-R2水平与肾功能密切相关。
