Relationship between low levels of circulating TRAIL and atheromatosis progression in patients with chronic kidney disease

PLoS One. 2018 Sep 11;13(9):e0203716. doi: 10.1371/journal.pone.0203716. eCollection 2018.

Abstract

Background: Chronic kidney disease (CKD) patients experience a high risk of cardiovascular disease (CV); however, the factors involved in CV-related morbidity and mortality in these patients have not been fully defined. Tumor necrosis factor related apoptosis-inducing ligand (TRAIL) is a cytokine, which exhibits pleiotropic activities on endothelial, vascular smooth muscle and inflammatory cells, with relevant effects on atheromatous plaque formation. On this basis, the present study aims to investigate the role of TRAIL in atheromatosis progression in CKD patients.

Methods: Circulating TRAIL levels were measured in 378 CKD patients belonging to the Spanish National Observatory of Atherosclerosis in Nephrology (NEFRONA) study. All patients were free of previous CV events. Carotid and femoral B-mode ultrasound was performed to detect the presence of plaque at baseline and after 24 months of follow-up.

Results: The lowest levels of TRAIL at baseline were significantly (p<0.05) associated with the appearance, after 24 months of follow-up, of at least two new atheromatous plaques in all territories and of one new plaque in the carotid artery, even after adjusting for CV risk factors. In addition, the patients with low levels of TRAIL at baseline were characterized by the presence of at least one hypoechoic plaque in the carotid artery. This association was significant (p<0.05) even after adjusting for CKD stage.

Conclusions: Overall, the results of our study suggest TRAIL as an assertable independent prognostic biomarker for atheromatosis plaque formation in CKD patients. This observation further supports the potential role of TRAIL for the prevention/treatment of CV disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Atherosclerosis / complications
  • Atherosclerosis / pathology*
  • Biomarkers / blood
  • Carotid Arteries / diagnostic imaging
  • Carotid Arteries / pathology
  • Disease Progression
  • Female
  • Humans
  • Male
  • Middle Aged
  • Prognosis
  • Renal Insufficiency, Chronic / complications
  • Renal Insufficiency, Chronic / diagnosis*
  • Renal Insufficiency, Chronic / pathology
  • Severity of Illness Index
  • TNF-Related Apoptosis-Inducing Ligand / blood*
  • Ultrasonography

Substances

  • Biomarkers
  • TNF-Related Apoptosis-Inducing Ligand

Grants and funding

The NEFRONA study was funded by a research grant from Abbvie and the Spanish government RETIC (RD16/0009/0011) and FIS PI16/01354. MVA is the recipient of the Italian Ministry of Health grant No. GR-2013-02358192. SG is the recipient of the "Associazione Italiana per la Ricerca sul Cancro, AIRC" fellowship, No. 18055. Moreover, the authors would like to thank Fondazione Dott. Carlo Fornasini (Poggio Renatico, Ferrara, Italy). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.