Tumor necrosis factor receptors 1 and 2 are associated with early glomerular lesions in type 2 diabetes.
Tumor necrosis factor receptors 1 and 2 are associated with early glomerular lesions in type 2 diabetes.
复制标题
肿瘤坏死因子受体1和2与2型糖尿病的早期肾小球病变有关。
DOI：
10.1038/ki.2015.278
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发表时间：
2016-01
影响因子：
19.6
通讯作者：
Krolewski AS
中科院分区：
文献类型：
--
作者：
Pavkov ME;Weil EJ;Fufaa GD;Nelson RG;Lemley KV;Knowler WC;Niewczas MA;Krolewski AS
血清肿瘤坏死因子受体1（TNFR 1）和2（TNFR 2）浓度升高与2型糖尿病终末期肾病风险增加密切相关。然而，当这些标记物升高时，对患者发生的早期肾小球结构病变知之甚少。在这里，我们研究了肿瘤坏死因子受体和肾小球结构之间的关系，在83名美国印第安人与2型糖尿病。血清肿瘤坏死因子受体和肾小球滤过率（GFR，碘酞酸盐）在研究检查中进行了测量，中位数为0.9个月内从经皮肾活检。通过斯皮尔曼相关性和多变量线性回归对TNFR与肾小球结构变量的关系进行量化，调整年龄、性别、糖尿病病程、血红蛋白A1 c、体重指数和平均动脉压。基线平均年龄为46岁，中位GFR为130 ml/min，中位白蛋白/肌酐比值为26 mg/g，中位TNFR 1为1500 pg/ml，中位TNFR 2为3284 pg/ml。经多变量校正后，TNFR 1和TNFR 2与内皮细胞开窗百分比和每个肾小球的总滤过表面积呈显著负相关。肾小球系膜体积分数、肾小球基底膜宽度、足细胞足突宽度、肾小球硬化百分比与肾小球系膜体积分数呈显著正相关。因此，TNFRs可能参与糖尿病肾病早期肾小球病变的发病机制。
Elevated serum tumor necrosis factor receptor 1 (TNFR1) and 2 (TNFR2) concentrations are strongly associated with increased risk of end-stage renal disease in type 2 diabetes. However, little is known about the early glomerular structural lesions that develop in patients when these markers are elevated. Here we examined the relationships between TNFRs and glomerular structure in 83 American Indians with type 2 diabetes. Serum TNFRs and glomerular filtration rates (GFR, iothalamate) were measured during a research exam performed within a median of 0.9 months from a percutaneous kidney biopsy. Associations of TNFRs with glomerular structural variables were quantified by Spearman's correlations and by multivariable linear regression after adjustment for age, gender, diabetes duration, hemoglobin A1c, body mass index, and mean arterial pressure. The baseline mean age was 46 years, median GFR 130 ml/min, median albumin/creatinine ratio 26 mg/g, median TNFR1 1500 pg/ml, and median TNFR2 3284 pg/ml. After multivariable adjustment, TNFR1 and TNFR2 significantly correlated inversely with the percentage of endothelial cell fenestration and the total filtration surface per glomerulus. There were significant positive correlations with mesangial fractional volume glomerular basement membrane width, podocyte foot process width, and percent of global glomerular sclerosis. Thus, TNFRs may be involved in the pathogenesis of early glomerular lesions in diabetic nephropathy.