Interrelationship of Multiple Endothelial Dysfunction Biomarkers with Chronic Kidney Disease

PLoS One. 2015 Jul 1;10(7):e0132047. doi: 10.1371/journal.pone.0132047. eCollection 2015.

Abstract

The interrelationship of multiple endothelial biomarkers and chronic kidney disease (CKD) has not been well studied. We measured asymmetric dimethylarginine (ADMA), L-arginine, soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular adhesion molecule-1 (sVCAM-1), soluble E-selectin (sE-selectin), von Willebrand factor (vWF), flow-mediated dilation (FMD), and nitroglycerin-induced dilation (NID) in 201 patients with CKD and 201 community-based controls without CKD. Multivariable analyses were used to examine the interrelationship of endothelial biomarkers with CKD. The multivariable-adjusted medians (interquartile ranges) were 0.54 (0.40, 0.75) in patients with CKD vs. 0.25 (0.22, 0.27) μmol /L in controls without CKD (p<0.0001 for group difference) for ADMA; 67.0 (49.6, 86.7) vs. 31.0 (27.7, 34.2) μmol/L (p<0.0001) for L-arginine; 230.0 (171.6, 278.6) vs. 223.9 (178.0, 270.6) ng/mL (p=0.55) for sICAM-1; 981.7 (782.6, 1216.8) vs. 633.2 (507.8, 764.3) ng/mL (p<0.0001) for sVCAM-1; 47.9 (35.0, 62.5) vs. 37.0 (28.9, 48.0) ng/mL (p=0.01) for sE-selectin; 1320 (1044, 1664) vs. 1083 (756, 1359) mU/mL (p=0.008) for vWF; 5.74 (3.29, 8.72) vs. 8.80 (6.50, 11.39)% (p=0.01) for FMD; and 15.2 (13.5, 16.9) vs. 19.1 (17.2, 21.0)% (p=0.0002) for NID, respectively. In addition, the severity of CKD was positively associated with ADMA, L-arginine, sVCAM-1, sE-selectin, and vWF and inversely associated with FMD and NID. Furthermore, FMD and NID were significantly and inversely correlated with ADMA, L-arginine, sVCAM-1, sE-selectin, and vWF. In conclusion, these data indicate that multiple dysfunctions of the endothelium were present among patients with CKD. Interventional studies are warranted to test the effects of treatment of endothelial dysfunction on CKD.

Publication types

  • Clinical Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Aged
  • Albuminuria / blood
  • Albuminuria / urine
  • Arginine / analogs & derivatives*
  • Arginine / blood*
  • Biomarkers
  • Blood Glucose / analysis
  • Cell Adhesion Molecules / blood*
  • Comorbidity
  • Creatinine / analysis
  • Diabetes Mellitus / blood
  • Diabetes Mellitus / epidemiology
  • Endothelium, Vascular / physiopathology*
  • Female
  • Humans
  • Hypercholesterolemia / blood
  • Hypercholesterolemia / epidemiology
  • Hypertension / blood
  • Hypertension / epidemiology
  • Inflammation
  • Kidney Function Tests
  • Lipids / blood
  • Male
  • Middle Aged
  • Nitric Oxide / metabolism
  • Renal Insufficiency, Chronic / blood*
  • Renal Insufficiency, Chronic / epidemiology
  • Risk
  • Sensitivity and Specificity
  • Thrombophilia / blood
  • Thrombophilia / etiology
  • Vasodilation
  • Young Adult
  • von Willebrand Factor / analysis*

Substances

  • Biomarkers
  • Blood Glucose
  • Cell Adhesion Molecules
  • Lipids
  • von Willebrand Factor
  • Nitric Oxide
  • N,N-dimethylarginine
  • Arginine
  • Creatinine