title: Serum Vascular Adhesion Protein-1 Predicts End-Stage Renal Disease in Patients with Type 2 Diabetes.
abstract: 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.
authors: Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
authors: Hung-Yuan
authors: HY
authors: Li
authors: Lo-Sheng Sanatorium and Hospital, Ministry of Health and Welfare, Taipei, Taiwan.
authors: Hung-An
authors: HA
authors: Lin
authors: Department of Internal Medicine, National Taiwan University Hospital Yun-Lin Branch, Yun-Lin, Taiwan.
authors: Feng-Jung
authors: FJ
authors: Nien
authors: Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
authors: Vin-Cent
authors: VC
authors: Wu
authors: Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
authors: Yi-Der
authors: YD
authors: Jiang
authors: Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
authors: Tien-Jyun
authors: TJ
authors: Chang
authors: Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
authors: Hsien-Li
authors: HL
authors: Kao
authors: Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.|Graduate Institute of Clinical Medicine, Medical College, National Taiwan University, Taipei, Taiwan.
authors: Mao-Shin
authors: MS
authors: Lin
authors: Chia Nan University of Pharmacy and Science, Tainan, Taiwan.
authors: Jung-Nan
authors: JN
authors: Wei
authors: Division of Cardiovascular Surgery, Department of Surgery, Taipei Medical University-Wan Fang Hospital, Taipei, Taiwan.
authors: Cheng-Hsin
authors: CH
authors: Lin
authors: Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
authors: Shyang-Rong
authors: SR
authors: Shih
authors: Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
authors: Chi-Sheng
authors: CS
authors: Hung
authors: Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.|Graduate Institute of Clinical Medicine, Medical College, National Taiwan University, Taipei, Taiwan.|Graduate Institute of Preventive Medicine, National Taiwan University School of Public Health, Taipei, Taiwan.
authors: Lee-Ming
authors: LM
authors: Chuang
mesh_terms: D000368:Aged; D006631:Amine Oxidase (Copper-Containing) / Q000097:blood*; D015415:Biomarkers; D015815:Cell Adhesion Molecules / Q000097:blood*; D015897:Comorbidity; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000150:complications* / Q000453:epidemiology / Q000401:mortality; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D053208:Kaplan-Meier Estimate; D007676:Kidney Failure, Chronic / Q000175:diagnosis* / Q000453:epidemiology / Q000209:etiology* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012307:Risk Factors; D013624:Taiwan / Q000453:epidemiology
chemical_list: D015415:Biomarkers; D015815:Cell Adhesion Molecules; C076668:AOC3 protein, human; D006631:Amine Oxidase (Copper-Containing)