Endothelial dysfunction and inflammation in asymptomatic proteinuria

Kidney Int. 2003 Feb;63(2):624-33. doi: 10.1046/j.1523-1755.2003.00768.x.


Background: Proteinuria is associated with vascular risk and a systemic increase in vascular permeability. Endothelial dysfunction occurs early in atherosclerosis and modulates vascular permeability. Vascular risk and chronic inflammation are associated. This study investigates whether the increased vascular permeability in proteinuria reflects systemic endothelial dysfunction and chronic inflammation.

Methods: Twenty-one patients with asymptomatic proteinuria (1.29 g/24 h; range 0.18 to 3.17) and 21 matched controls were studied. Microvascular endothelial function was assessed using acetylcholine iontophoresis. Maximum microvascular hyperemia (MMH) was assessed by flux response to local skin heating. Macrovascular endothelial function was assessed by flow-associated dilation (FAD) in the brachial artery using ultrasound. von Willebrand factor (vWF) was measured as a marker of endothelial activation. Low-grade inflammation was assessed by measurement of circulating C-reactive protein (CRP) values using a high sensitivity assay.

Results: FAD was impaired in proteinuric subjects (AP) compared to controls [1.8 (0.2 to 5.3) AP vs. 3.8 (1.5 to 6.2) C %; P = 0.014]. There was no significant difference between groups in MMH or in the response to acetylcholine iontophoresis. The AP group had a higher CRP [4.0 (0.5 to 39.0) AP vs. 0.2 (0.1 to 21.3) C mg/L; P < 0.001] and tendency to higher vWF [101.5 (67.0 to 197.0) AP vs. 77.5 (45.0 to 185.0) C IU/dL; P = 0.046] compared to controls. In the AP, but not control, group there was an inverse correlation between CRP and microvascular function as determined by acetylcholine iontophoresis (r = -0.509; P = 0.018).

Conclusions: In AP subjects there is evidence of macrovascular endothelial dysfunction remote from the kidney and of low-grade inflammation that is associated with microvascular endothelial dysfunction.

MeSH terms

  • Adult
  • Biomarkers / analysis
  • C-Reactive Protein / metabolism
  • Capillary Permeability
  • Case-Control Studies
  • Endothelium, Vascular / pathology*
  • Endothelium, Vascular / physiopathology*
  • Female
  • Humans
  • Male
  • Microcirculation
  • Middle Aged
  • Proteinuria / complications*
  • Proteinuria / physiopathology*
  • Regional Blood Flow
  • Solubility
  • Vasculitis / etiology*
  • Vasodilation
  • von Willebrand Factor / metabolism


  • Biomarkers
  • von Willebrand Factor
  • C-Reactive Protein