Endothelial injury is closely related to osteopontin and TNF receptor-mediated inflammation in end-stage renal disease

Cytokine. 2019 Sep:121:154729. doi: 10.1016/j.cyto.2019.05.016. Epub 2019 May 30.

Abstract

Background: Endothelial dysfunction, inflammation and active mineralization are key processes involved in cardiovascular burden in end stage renal disease (ESRD). Serum (soluble) thrombomodulin (sTM) is an established marker of endothelial injury.

Patients: 80 patients in ESRD were recruited consecutively. Baseline distribution of sex, age, main comorbidities and Framingham score was similar. A biochemical panel including sTM, intact PTH (iPTH), interleukin-6 (IL-6), pentraxin 3 (PTX3), fibroblast growth factor 23 (FGF-23), osteopontin (OPN), osteoprotegerin (OPG), osteocalcin (OC), osteonectin (ON), soluble tumor necrosis factor receptor type 2 (TNFR2), transforming growth factor-β (TGF-β), hepatocyte growth factor (HGF), vascular endothelial growth factor receptor type 2 (sVEGFR2) and stromal cell-derived factor 1α (SDF1α) was investigated in each patient. Samples obtained while establishing haemodialysis (HD) access were stained for radial artery calcifications (RACs) with Alizarin red and examined histologically.

Results: After adjustment for HD status, sTM showed a significant positive correlation with serum creatinine, TNFR2, OPN, HGF, SDF1α, sVEGFR2, Pi, iPTH, FGF-23, OPG, OC and ON. In forward stepwise multiple regression, serum creatinine, TNFR2, and OPN were identified as significant, independent predictors of sTM. Grades 1-3 of RACs correlated with sTM (R = 0.50, p = 0.017), while grade 3 RACs were significantly associated with higher sTM (p = 0.02) than less advanced lesions.

Conclusion: Among novel renal and cardiovascular biomarkers, OPN and TNFR2 are closely related to sTM. This may link endothelial damage, vascular remodeling and inflammation. Progression of RAC parallels a presumed compensatory rise in sTM, reflecting endothelial injury. sTM has an intricate role in endothelial function and potential clinical and prognostic applications.

Keywords: End-stage renal disease; Inflammation; Osteopontin; TNF receptors; Thrombomodulin; Vascular remodelling.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Biomarkers / blood
  • Calcinosis / blood
  • Cardiovascular Diseases / blood
  • Endothelial Cells / metabolism*
  • Endothelial Cells / pathology*
  • Female
  • Fibroblast Growth Factor-23
  • Humans
  • Inflammation / pathology*
  • Kidney Failure, Chronic / metabolism*
  • Kidney Failure, Chronic / pathology*
  • Male
  • Middle Aged
  • Osteopontin / metabolism*
  • Radial Artery / metabolism
  • Radial Artery / pathology
  • Receptors, Tumor Necrosis Factor, Type II / metabolism*
  • Regression Analysis
  • Renal Dialysis
  • Risk Factors
  • Thrombomodulin / blood

Substances

  • Biomarkers
  • FGF23 protein, human
  • Receptors, Tumor Necrosis Factor, Type II
  • Thrombomodulin
  • Osteopontin
  • Fibroblast Growth Factor-23