title: Tumor Necrosis Factor-Alpha and 8-Hydroxy-2'-Deoxyguanosine are Associated with Elevated Urinary Angiopoietin-2 Level in Type 2 Diabetic Patients with Albuminuria.
abstract: OBJECTIVE
  We previously showed that urine and serum Angiopoietin-2 (Ang-2) levels increased significantly with the degree of albuminuria in diabetes patients, but the reasons remain unclear. Consequently we aimed to determine whether there was an association between Ang-2, inflammatory cytokines (TNF-α and IL-18) and reactive oxygen species (8-OHdG and SOD) in type 2 diabetes patients with albuminuria.
  
  
  METHODS
  This retrospective study evaluated 113 patients with type 2 diabetes and normoalbuminuria, microalbuminuria, or macroalbuminuria and 30 healthy controls. Serum and urine TNF-α, IL-18 and 8-OHdG levels were measured by ELISA. Superoxide dismutase (SOD) activity was determined by spectrophotometry.
  
  
  RESULTS
  Serum and urine TNF-α, IL-18 and 8-OHdG levels increased significantly with the degree of albuminuria, and were positively correlated with increased Ang-2. In contrast, SOD activity decreased with the degree of albuminuria and was negatively correlated with Ang-2. Multivariable linear regression analysis revealed that serum Ang-2 level was independently associated with serum levels of TNF-α (P<0.001), 8-OHdG (P=0.001), and IL-18 (P=0.003). Urinary Ang-2 level was independently associated with urinary TNF-α (P<0.001) and 8-OHdG (P=0.004) levels.
  
  
  CONCLUSIONS
  TNF-α and 8-OHdG are associated with elevated urinary Angiopoietin-2 levels in type 2 diabetic patients with albuminuria.
authors.affiliation: Department of Nephrology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
authors.forename: Fang-Fang
authors.initials: FF
authors.lastname: He
authors.forename: Hui-Qing
authors.initials: HQ
authors.lastname: Li
authors.forename: Qing-Xian
authors.initials: QX
authors.lastname: Huang
authors.forename: Qiu-Yuan
authors.initials: QY
authors.lastname: Wang
authors.forename: Hua-Jun
authors.initials: HJ
authors.lastname: Jiang
authors.forename: Shan
authors.initials: S
authors.lastname: Chen
authors.forename: Hua
authors.initials: H
authors.lastname: Su
authors.forename: Chun
authors.initials: C
authors.lastname: Zhang
authors.forename: Yu-Mei
authors.initials: YM
authors.lastname: Wang
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D000328:Adult; D000419:Albuminuria / Q000097:blood*; D042702:Angiopoietin-2 / Q000652:urine*; D003430:Cross-Sectional Studies; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000097:blood*; D005260:Female; D006801:Humans; D020382:Interleukin-18 / Q000378:metabolism; D007678:Kidney Glomerulus / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D012189:Retrospective Studies; D013482:Superoxide Dismutase / Q000097:blood / Q000378:metabolism; D000072105:Superoxide Dismutase-1; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: C586513:ANGPT2 protein, human; D042702:Angiopoietin-2; D020382:Interleukin-18; D017382:Reactive Oxygen Species; C000606290:SOD1 protein, human; D014409:Tumor Necrosis Factor-alpha; D000080242:8-Hydroxy-2'-Deoxyguanosine; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases; C498910:NOX4 protein, human; D003849:Deoxyguanosine