The relationship between inflammation, endothelial dysfunction and proteinuria in patients with diabetic nephropathy

Scand J Clin Lab Invest. 2011 Nov;71(7):606-12. doi: 10.3109/00365513.2011.598944. Epub 2011 Aug 24.

Abstract

Objectives: Diabetic nephropathy (DN) is a major manifestation of microangiopathy in patients with Diabetes Mellitus (DM). Inflammation is one of the major factors in the formation of endothelial dysfunction. Endothelial dysfunction is a major contributor to the complications of DM. The aim of the present study was to investigate the possible relationship between inflammation, endothelial dysfunction and proteinuria in patients with diabetic nephropathy.

Materials and methods: Plasma TNF-α and IL-6, pro-inflammatory cytokines, concentrations were measured in 25 patients with DN and in 30 diabetic control subjects. Also, we evaluated the markers of endothelial dysfunction such as flow mediated dilatation (FMD), nitrate-mediated dilatation (NMD) and carotid intima-media thickness (CIMT).

Results: TNF-α, IL-6 and high-sensitivity C-reactive protein concentrations were significantly higher (p = 0.012, p = 0.006 and p < 0.001, respectively) in the patients with DN than the controls. And, urinary protein concentrations were significantly higher (p < 0.001) but eGFR levels were significantly lower (p < 0.001) in the patients with DN. FMD was significantly lower in DN patients (p < 0.001). We have observed that FMD correlated negatively with body mass index (r = -0.424, p < 0.05). And there was also a positive correlation between TNF-α and urinary protein concentrations in the patients with DN (p < 0.05).

Conclusion: TNF-α, IL-6, hsCRP and urinary protein concentrations are higher in the DN patients. There were no correlations among pro-inflammatory cytokines concentrations and markers of vascular endotelial disfunction. These findings did not show vascular endothelial dysfunction, but may indicate glomerular endothelial dysfunction.

MeSH terms

  • Biomarkers / blood*
  • Blood Vessels / metabolism
  • C-Reactive Protein / analysis
  • Carotid Intima-Media Thickness
  • Diabetes Complications
  • Diabetes Mellitus / blood*
  • Diabetes Mellitus / physiopathology
  • Diabetic Nephropathies / blood*
  • Diabetic Nephropathies / complications
  • Diabetic Nephropathies / physiopathology
  • Endothelium / metabolism
  • Endothelium / physiopathology*
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Glomerular Filtration Rate
  • Humans
  • Inflammation / blood*
  • Inflammation / complications
  • Inflammation / physiopathology
  • Interleukin-6 / blood
  • Kidney Glomerulus / metabolism
  • Kidney Glomerulus / physiopathology*
  • Male
  • Middle Aged
  • Proteinuria / blood*
  • Proteinuria / complications
  • Proteinuria / physiopathology
  • Tumor Necrosis Factor-alpha / blood
  • Vasodilation

Substances

  • Biomarkers
  • Interleukin-6
  • Tumor Necrosis Factor-alpha
  • C-Reactive Protein