Cardiovascular risk markers associated with arterial calcification in patients with chronic kidney disease Stages 3 and 4

Abstract

Background: The contribution of pro-inflammatory markers to cardiovascular (CV) risk and vascular calcification in chronic kidney disease (CKD) remains largely to be elucidated. We investigated the association between plasma levels of several biomarkers and calcification volume in three different vascular beds in CKD Stages 3 and 4 patients.

Methods: This is a cross-sectional, exploratory study in patients with an estimated glomerular filtration rate (eGFR) ≥20 and ≤45 mL/min/1.73 m² and serum phosphorus ≥3.5 and <6.0 mg/dL enrolled in a previously published randomized, double blind, placebo-controlled single-centre trial. Ethylenediaminetetraacetic acid (EDTA) plasma samples were collected at baseline before patients received study medication and analysed for the presence of a number of biomarkers. Coronary artery calcium (CAC), thoracic aortic calcification (TAC) and abdominal aortic calcification (AAC) volumes were measured using standard electron-beam computed tomography protocols. Associations were adjusted for age, sex, smoking, body mass index, diabetes mellitus status, low-density lipoprotein cholesterol (LDL-C), systolic blood pressure and eGFR.

Results: Associations with CAC were found for β2-microglobulin (B2M), fibroblast growth factor 23 (FGF23), interleukin-8 (IL-8) and IL-18. AAC was associated with: B2M, FGF23 and IL-2 receptor alpha (IL-2 RA). TAC was associated with: B2M, FGF23, IL-2 RA, IL-18 and tumour necrosis factor receptor type I. For most of the analysed biomarkers, there were non-significant trends of associations with calcification.

Conclusions: This exploratory study found that elevated plasma levels of several inflammatory biomarkers are significantly associated with arterial calcification in CKD Stages 3 and 4 patients. A greater understanding of inflammation and calcification in CKD patients may help the development of CV risk-assessment algorithms for better management of these patients.

Keywords: arterial calcification; biomarkers; cardiovascular risk; chronic kidney disease; inflammation.

Fig. 1.

Standardized coefficient of association and 95% CIs between plasma levels of the assayed biomarkers and (a) CAC volume; (b) AAC volume; (c) TAC volume, respectively. The size of the black box indicates sample size. B2M, β2-microglobulin; FGF23, fibroblast growth factor 23 C-terminal; IL-18, interleukin-18; IL-8, interleukin-8; IL2.RA, interleukin-2 receptor alpha; LAP.TGFB1, latency-associated peptide transforming growth factor β1; MCP1, monocyte chemotactic protein 1; OPG, osteoprotegerin; OPN, osteopontin; MICA, major histocompatibility complex Class I-related chain A; MIP1BETA, macrophage inflammatory protein 1 beta; MMP2, matrix metalloproteinase-2; NGAL, neutrophil gelatinase-associated lipocalin; TIMP1, tissue inhibitor of metalloproteinases 1; TNFRI, tumour necrosis factor receptor Type I.