Tumor Necrosis Factor-Alpha and 8-Hydroxy-2'-Deoxyguanosine are Associated with Elevated Urinary Angiopoietin-2 Level in Type 2 Diabetic Patients with Albuminuria

Kidney Blood Press Res. 2015;40(4):355-65. doi: 10.1159/000368510. Epub 2015 Jun 20.

Abstract

Background/aims: 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.

Conclusion: TNF-α and 8-OHdG are associated with elevated urinary Angiopoietin-2 levels in type 2 diabetic patients with albuminuria.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 8-Hydroxy-2'-Deoxyguanosine
  • Adult
  • Albuminuria / blood*
  • Angiopoietin-2 / urine*
  • Cross-Sectional Studies
  • Deoxyguanosine / analogs & derivatives*
  • Deoxyguanosine / metabolism
  • Diabetes Mellitus, Type 2 / blood*
  • Female
  • Humans
  • Interleukin-18 / metabolism
  • Kidney Glomerulus / metabolism
  • Male
  • Middle Aged
  • NADPH Oxidase 4
  • NADPH Oxidases / metabolism
  • Reactive Oxygen Species / metabolism
  • Retrospective Studies
  • Superoxide Dismutase / blood
  • Superoxide Dismutase / metabolism
  • Superoxide Dismutase-1
  • Tumor Necrosis Factor-alpha / metabolism*

Substances

  • ANGPT2 protein, human
  • Angiopoietin-2
  • Interleukin-18
  • Reactive Oxygen Species
  • SOD1 protein, human
  • Tumor Necrosis Factor-alpha
  • 8-Hydroxy-2'-Deoxyguanosine
  • Superoxide Dismutase
  • Superoxide Dismutase-1
  • NADPH Oxidase 4
  • NADPH Oxidases
  • NOX4 protein, human
  • Deoxyguanosine