血清血管黏附蛋白-1可预测2型糖尿病患者的终末期肾病
Serum Vascular Adhesion Protein-1 Predicts End-Stage Renal Disease in Patients with Type 2 Diabetes.
作者信息
Li Hung-Yuan, Lin Hung-An, Nien Feng-Jung, Wu Vin-Cent, Jiang Yi-Der, Chang Tien-Jyun, Kao Hsien-Li, Lin Mao-Shin, Wei Jung-Nan, Lin Cheng-Hsin, Shih Shyang-Rong, Hung Chi-Sheng, Chuang Lee-Ming
机构信息
Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
Lo-Sheng Sanatorium and Hospital, Ministry of Health and Welfare, Taipei, Taiwan.
出版信息
PLoS One. 2016 Feb 4;11(2):e0147981. doi: 10.1371/journal.pone.0147981. eCollection 2016.
BACKGROUND
Diabetes is the leading cause of end-stage renal disease (ESRD) worldwide. Vascular adhesion protein-1 (VAP-1) participates in inflammation and catalyzes the deamination of primary amines into aldehydes, hydrogen peroxide, and ammonia, both of which are involved in the pathogenesis of diabetic complications. We have shown that serum VAP-1 is higher in patients with diabetes and in patients with chronic kidney disease (CKD), and can predict cardiovascular mortality in subjects with diabetes. In this study, we investigated if serum VAP-1 can predict ESRD in diabetic subjects.
METHODS
In this prospective cohort study, a total of 604 type 2 diabetic subjects were enrolled between 1996 to 2003 at National Taiwan University Hospital, Taiwan, and were followed for a median of 12.36 years. The development of ESRD was ascertained by linking our database with the nationally comprehensive Taiwan Society Nephrology registry. Serum VAP-1 concentrations at enrollment were measured by time-resolved immunofluorometric assay.
RESULTS
Subjects with serum VAP-1 in the highest tertile had the highest incidence of ESRD (p<0.001). Every 1-SD increase in serum VAP-1 was associated with a hazard ratio of 1.55 (95%CI 1.12-2.14, p<0.01) for the risk of ESRD, adjusted for smoking, history of cardiovascular disease, body mass index, hypertension, HbA1c, duration of diabetes, total cholesterol, use of statins, ankle-brachial index, estimated GFR, and proteinuria. We developed a risk score comprising serum VAP-1, HbA1c, estimated GFR, and proteinuria, which could predict ESRD with good performance (area under the ROC curve = 0.9406, 95%CI 0.8871-0.9941, sensitivity = 77.3%, and specificity = 92.8%). We also developed an algorithm based on the stage of CKD and a risk score including serum VAP-1, which can stratify these subjects into 3 categories with an ESRD risk of 0.101%/year, 0.131%/year, and 2.427%/year, respectively.
CONCLUSIONS
In conclusion, serum VAP-1 can predict ESRD and is a useful biomarker to improve risk stratification in type 2 diabetic subjects.
背景
糖尿病是全球终末期肾病（ESRD）的主要病因。血管黏附蛋白-1（VAP-1）参与炎症反应，并催化伯胺脱氨生成醛、过氧化氢和氨，这两者均参与糖尿病并发症的发病机制。我们已经表明，糖尿病患者和慢性肾脏病（CKD）患者的血清VAP-1水平较高，并且可以预测糖尿病患者的心血管死亡率。在本研究中，我们调查了血清VAP-1是否可以预测糖尿病患者的ESRD。
方法
在这项前瞻性队列研究中，1996年至2003年期间，台湾大学附属医院共纳入了604例2型糖尿病患者，并对他们进行了为期12.36年的中位数随访。通过将我们的数据库与全国综合性的台湾肾脏病学会登记处相链接，确定ESRD的发生情况。入组时血清VAP-1浓度通过时间分辨免疫荧光测定法进行测量。
结果
血清VAP-1处于最高三分位数的受试者ESRD发病率最高（p<0.001）。血清VAP-1每增加1个标准差，ESRD风险的风险比为1.55（95%CI 1.12-2.14，p<0.01），对吸烟、心血管疾病史、体重指数、高血压、糖化血红蛋白、糖尿病病程、总胆固醇、他汀类药物使用、踝臂指数、估计肾小球滤过率和蛋白尿进行了校正。我们制定了一个风险评分，包括血清VAP-1、糖化血红蛋白、估计肾小球滤过率和蛋白尿，该评分可以很好地预测ESRD（ROC曲线下面积=0.9406，95%CI 0.8871-0.9941，敏感性=77.3%，特异性=92.8%）。我们还基于CKD分期和包括血清VAP-1的风险评分开发了一种算法，该算法可以将这些受试者分为3类，ESRD风险分别为每年0.101%、每年0.131%和每年2.427%。
结论
总之，血清VAP-1可以预测ESRD，是改善2型糖尿病患者风险分层的有用生物标志物。
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