2型糖尿病患者血清TNF-α水平与糖尿病肾脏疾病相关性研究

黄若妃　陈天喜　陈娟　夏静瑶　陈福宇

[摘要] 目的 探討2型糖尿病患者外周血中TNF-α水平与糖尿病肾脏疾病的相关性以及外周血TNF-α水平用于糖尿病肾脏疾病患者早期诊断的临床价值。 方法 选择2018年9月至2019年9月永康市第一人民医院就诊的DKD患者50例，设为糖尿病肾脏疾病组（DKD组），并根据患者尿白蛋白/尿肌酐将DKD患者分为微量蛋白尿组（n=32）、大量蛋白尿组（n=18），选同期T2DM不合并DKD患者200例，设为单纯糖尿病组（T2DM组）。检测并比较分析两组患者UACR、肾小球滤过率，检测并分析T2DM组患者和DKD组患者以及DKD患者两个亚组间TNF-α水平差异，采用 Pearson或Spearman分析外周血TNF-α与eGFR或UACR的相关性，采用 Logistic 多元回归分析法分析TNF-α水平与DKD的关系，最后绘制ROC曲线分析TNF-α、eGFR或UACR用于DKD诊断的特异性和敏感性。 结果 DKD组血清TNF-α水平高于T2DM组患者，且大量蛋白尿组血清TNF-α水平高于微量蛋白尿和单纯糖尿病组;TNF-α高水平是 DKD 的高危因素;血清TNF-α分别与 UACR 呈正相关（P<0.05），与 eGFR 呈负相关。ROC曲线分析显示，外周血TNF-α水平检测DKD的曲线下面积为 0.893，95%可信区间为0.675～1.000，敏感性和特异性分别为81.3%和89.3%，高于eGFR或UACR检测DKD的敏感性（73.4%，75.1%）和特异性（80.1%，83.5%）。 结论 TNF-α可能参与DKD进程，在DKD病情变化中发挥重要作用，并在一定程度上反映肾小球滤过率，可作为 DKD 早期诊断的指标。

[关键词] 2型糖尿病;糖尿病肾脏疾病;肿瘤坏死因子α;蛋白尿

[中图分类号] R587.2          [文献标识码] A          [文章编号] 1673-9701（2021）04-0030-04

Study of correlation between serum TNF-α level and diabetic kidney disease in patients with type 2 diabetes mellitus

HUANG Ruofei   CHEN Tianxi   CHEN Juan   XIA Jingyao   CHEN Fuyu

Department of Endocrinology， the First People′s Hospital of Yongkang City in Zhejiang Province， Yongkang 321300， China.

[Abstract] Objective To explore the correlation between TNF-α level in peripheral blood and diabetic kidney disease（DKD） in patients with type 2 diabetes mellitus（T2DM） and the clinical value of TNF-α level in peripheral blood in early diagnosis of DKD. Methods A total of 50 patients with DKD admitted to the First People′s Hospital of Yongkang from September 2018 to September 2019 were selected as DKD group. According to urinary albumin and creatinine， patients with DKD were divided into microalbuminuria group（32 cases） and massive proteinuria group（18 cases）. A total of 200 T2DM patients without DKD were selected as simple diabetes group. Urine Albumin-to-Creatinine Ratio（UACR） and glomerular filtration rate were detected and compared between the two groups. The differences of tumor necrosis factor-α（TNF-α） level between T2DM patients， DKD patients and DKD patients in two subgroups were detected and analyzed. Pearson or Spearman was used to analyze the correlation between TNF-α in peripheral blood and eGFR or UACR. Multiple Logistic regression analysis was used to analyze the relationship between TNF-α level and DKD. Finally， ROC curve was drawn to analyze the specificity and sensitivity of TNF-α， eGFR or UACR in the diagnosis of DKD. Results The serum TNF-α level in DKD group was higher than that in T2DM group， and the serum TNF-α level in massive proteinuria group was higher than that in microalbuminuria and simple diabetes group. The high level of TNF-α was a high-risk factor of DKD. Serum TNF-α was positively correlated with UACR（P<0.05） and negatively correlated with eGFR. ROC analyses showed that the area under the curve of peripheral blood TNF-α in the detection of DKD was 0.893， and the 95% confidence interval was 0.675-1.000. The sensitivity and specificity were 81.3% and 89.3%， respectively， which were higher than those of eGFR（sensitivity： 73.4%; specificity： 80.1%） or UACR（sensitivity： 75.1%; specificity： 83.5%）. Conclusion TNF-α may participate in the process of DKD， playing an important role in the change of DKD， and reflecting glomerular filtration rate to a certain extent， which can be used as a method for early diagnosis of DKD.

[Key words] Type 2 diabetes mellitus; Diabetic kidney disease; Tumor necrosis factor alpha; Proteinuria

糖尿病肾脏疾病（Diabetic kidney disease，DKD）是糖尿病患者常见的微血管并发症之一，也是糖尿病发病和糖尿病相关死亡的关键原因之一，研究指出40%～50%的1型糖尿病（Type 1 diabetes，T1DM）或2型糖尿病（Type 2 diabetes，T2DM）患者最终都会发展为DKD[1-3]。此外，DKD也是诱发终末期肾病（End-stage renal disease，ESRD）的主要原因之一，通過诱发ESRD而导致患者严重的肾脏损伤和肾功能障碍，进而导致患者的不良预后和死亡率的升高[4]。流行病学统计指出，中国糖尿病患者中DKD的发病率高达52.2%，DKD已成为严重的公共健康问题，严重影响人民健康。……