Serum Vascular Adhesion Protein-1 Predicts End-Stage Renal Disease in Patients with Type 2 Diabetes.
Serum Vascular Adhesion Protein-1 Predicts End-Stage Renal Disease in Patients with Type 2 Diabetes.
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DOI：
10.1371/journal.pone.0147981
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Chuang LM
中科院分区：
文献类型：
--
作者：
Li HY;Lin HA;Nien FJ;Wu VC;Jiang YD;Chang TJ;Kao HL;Lin MS;Wei JN;Lin CH;Shih SR;Hung CS;Chuang LM
糖尿病是全球终末期肾病（ESRD）的主要原因。血管粘附蛋白-1（VAP-1）参与炎症反应并催化伯胺脱氨为醛、过氧化氢和氨，这两者都参与糖尿病并发症的发病机制。我们已经表明，血清VAP-1在糖尿病患者和慢性肾脏病（CKD）患者中较高，并且可以预测糖尿病受试者的心血管死亡率。在这项研究中，我们调查了血清VAP-1是否可以预测糖尿病患者的ESRD。在这项前瞻性队列研究中，1996年至2003年期间在台湾国立台湾大学医院共招募了604例2型糖尿病受试者，并随访了中位数为12.36年。终末期肾病的发展是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联系起来确定的。血清VAP-1浓度在登记时通过时间分辨免疫荧光法测定。血清VAP-1水平在最高三分位数的受试者ESRD的发病率最高（p<0.001）。经吸烟、心血管疾病史、体重指数、高血压、HbA 1c、糖尿病病程、总胆固醇、他汀类药物使用、踝臂指数、估计GFR和蛋白尿校正后，血清VAP-1每增加1个标准差，患终末期肾病的风险比为1.55（95%CI 1.12-2.14，p<0.01）。我们开发了一个包括血清VAP-1、HbA 1c、估计的GFR和蛋白尿的风险评分，该评分可以预测ESRD，具有良好的性能（ROC曲线下面积= 0.9406，95%CI 0.8871-0.9941，灵敏度= 77.3%，特异性= 92.8%）。我们还开发了一种基于CKD分期和包括血清VAP-1在内的风险评分的算法，该算法可将这些受试者分为3类，ESRD风险分别为0.101%/年、0.131%/年和2.427%/年。总之，血清VAP-1可以预测终末期肾病，是一个有用的生物标志物，以改善2型糖尿病患者的危险分层。
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. 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. 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. In conclusion, serum VAP-1 can predict ESRD and is a useful biomarker to improve risk stratification in type 2 diabetic subjects.