Asymmetric dimethylarginine and angiopoietin-like protein-2 are independent predictors of cardiovascular risk in pre-dialysis non-diabetic chronic kidney disease patients

Int Urol Nephrol. 2020 Jul;52(7):1321-1328. doi: 10.1007/s11255-020-02484-0. Epub 2020 May 14.

Abstract

Background: Chronic kidney disease (CKD) is associated with increased cardiovascular (CVD) morbidity and mortality. Hence, this study was carried out to assess the biomarkers of endothelial dysfunction and inflammation as predictors of CVD risk in Indian patients with CKD.

Methods: In this case control study, we recruited 43 patients with CKD and 43 healthy control volunteers. Circulating levels of endothelial dysfunction markers [asymmetric dimethylarginine (ADMA), angiopoietin-like protein-2 (ANGPTL2), matrix metallopeptidase 9 (MMP-9)] and systemic inflammation [high-sensitivity C-reactive protein (hs-CRP)] were assessed in the study population. All study participants underwent brachial artery flow mediated dilation (FMD) to estimate endothelial dysfunction. Disease severity (e-GFR) was assessed by a nephrologist.

Results: CKD patients showed markedly elevated levels of ADMA, ANGPTL2, MMP-9, and hs-CRP. FMD and eGFR were significantly decreased in cases, as compared to the controls. ADMA, ANGPTL2, MMP-9 and hs-CRP showed significant positive correlation with one another and significant negative correlation with FMD and disease severity. We also observed a significant negative correlation of FMD with disease severity and duration of CKD. In the multiple linear regression model, ADMA and ANGPTL2 were found to be independent predictors of FMD.

Conclusion: In CKD patients, there is significantly increased endothelial dysfunction and systemic inflammation, which showed a positive correlation with disease severity. Thus, the markers of endothelial dysfunction such as ADMA and ANGPTL2 can be used as predictors of CVD risk in CKD.

Keywords: Cardiovascular disease risk; Chronic kidney disease; Endothelial dysfunction; Flow-mediated dilation; High sensitivity C-reactive protein; Inflammation.

MeSH terms

  • Adolescent
  • Adult
  • Angiopoietin-Like Protein 2
  • Angiopoietin-like Proteins / blood*
  • Arginine / analogs & derivatives*
  • Arginine / blood
  • Biomarkers / blood
  • Cardiovascular Diseases / blood*
  • Cardiovascular Diseases / epidemiology*
  • Cardiovascular Diseases / etiology
  • Case-Control Studies
  • Endothelium, Vascular / physiopathology
  • Female
  • Humans
  • Male
  • Middle Aged
  • Predictive Value of Tests
  • Renal Insufficiency, Chronic / blood*
  • Renal Insufficiency, Chronic / complications
  • Renal Insufficiency, Chronic / physiopathology
  • Risk Assessment
  • Young Adult

Substances

  • ANGPTL2 protein, human
  • Angiopoietin-Like Protein 2
  • Angiopoietin-like Proteins
  • Biomarkers
  • N,N-dimethylarginine
  • Arginine