title: Endothelial dysfunction and inflammation in asymptomatic proteinuria.
abstract: 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.
authors.affiliation: Institute of Biomedical and Clinical Science, Peninsula Medical School, and Renal Unit, Royal Devon and Exeter Hospital, Exeter, United Kingdom. k.paisley@virgin.net
authors.forename: Karen E
authors.initials: KE
authors.lastname: Paisley
authors.forename: Martin
authors.initials: M
authors.lastname: Beaman
authors.forename: John E
authors.initials: JE
authors.lastname: Tooke
authors.forename: Vidya
authors.initials: V
authors.lastname: Mohamed-Ali
authors.forename: Gordon D O
authors.initials: GD
authors.lastname: Lowe
authors.forename: Angela C
authors.initials: AC
authors.lastname: Shore
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000032:analysis; D002097:C-Reactive Protein / Q000378:metabolism; D002199:Capillary Permeability; D016022:Case-Control Studies; D004730:Endothelium, Vascular / Q000473:pathology* / Q000503:physiopathology*; D005260:Female; D006801:Humans; D008297:Male; D008833:Microcirculation; D008875:Middle Aged; D011507:Proteinuria / Q000150:complications* / Q000503:physiopathology*; D012039:Regional Blood Flow; D012995:Solubility; D014657:Vasculitis / Q000209:etiology*; D014664:Vasodilation; D014841:von Willebrand Factor / Q000378:metabolism
chemical_list: D015415:Biomarkers; D014841:von Willebrand Factor; D002097:C-Reactive Protein