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

Abstract

BackgroundThe 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.MethodsThis 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.ResultsAssociations 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.ConclusionsThis 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.

Gender Specific Association between Serum Fibroblast Growth Factor 23/α-Klotho and Coronary Artery and Aortic Valve Calcification

“…This suggested that the risk factors for CAC and AVC are different, although coronary artery calcium and aortic valve calcium are, in general, positively correlated 27) . This notion might be supported by the findings in previous reports that lipoprotein(a) levels were associated with aortic valve calcification but not with coronary calcification 37) , was associated with greater coronary artery calcium volume among patients with CKD stages 3 and 4 33) . However, in several studies, including that of Kiu Weber et al, whether the observed association was independent of calcium/phosphate metabolism-related parameters was not assessed 22,33,34) .…”

“…This notion might be supported by the findings in previous reports that lipoprotein(a) levels were associated with aortic valve calcification but not with coronary calcification 37) , was associated with greater coronary artery calcium volume among patients with CKD stages 3 and 4 33) . However, in several studies, including that of Kiu Weber et al, whether the observed association was independent of calcium/phosphate metabolism-related parameters was not assessed 22,33,34) . Such adjustment should be performed to assess the statistical independence of the association, particularly because in the mice model of the genetic deletion of FGF23 and -Klotho, further deletion of vitamin D 1 -hydroxylase, leading to a decrease in serum 1,25(OH)2D, suppressed the ectopic arterial calcification observed 31,35) .…”

MICS, an easily ignored contributor to arterial calcification in CKD patients

“…Wang et al (101) observed that increased circulating inflammatory proteins such as CRP and IL-6 predicted a worse prognosis with AC in CKD patients. Similarly, in a cross-sectional study, Kiu et al (45) demonstrated that elevated plasma levels of several inflammatory biomarkers such as interleukin-8 (IL-8) and interleukin-18 (IL-18) are significantly associated with AC in CKD stages 3 and 4 patients. Moreover, high TNF-␣ and interleukin-1 (IL-1) levels were shown to progress AC in patients with CKD (63).…”

Phosphate Toxicity in CKD: The Killer among Us

“…Cardiovascular disease is the leading cause of death in patients with CKD in a manner independent of risk factors, such as a history of cardiovascular disease or the presence of documented proteinuria (78,79). The increased morbidity and mortality resulting from cardiovascular disease are associated with vascular calcification in these patients.…”