Coronary artery calcification, ADMA, and insulin resistance in CKD patients

Abstract

Background and objectives: It is known that coronary artery calcification (CAC) develops in chronic kidney disease (CKD) before initiation of renal replacement therapy, and factors associated with CKD mineral and bone disorders (CKD-MBDs) are involved. However, little information is available about any association between plasma levels of asymmetric dimethylarginine (ADMA), insulin resistance, and CAC.

Design, setting, participants, & measurements: A total of 111 CKD patients (79 men, 32 women; glomerular filtration rate [GFR] median, 33.7 ml/min per 1.73 m(2)), free of cardiovascular disease, were consecutively recruited along with 30 age-matched healthy subjects. Coronary artery calcification scores (CACS) were measured by multidetector-row CT according to Agatston score.

Results: In CKD patients, CACS was distributed widely from 0 to 2901, while in age-matched, healthy control subjects (n = 30), CACS showed a range from 0 to 307. GFR had a significant negative correlation with CACS. Plasma ADMA levels were negatively correlated with GFR and positively correlated with CACS. When CACS was divided into quartiles (<50, n = 56; 50 to 300, n = 24; 300 to 600, n = 14; >600, n = 17), the patients with CACS >600 had significantly higher values of HOMA-IR, plasma ADMA levels, and fibrinogen along with serum levels of phosphorus, compared with those in patients having CACS <50. Multivariate regression analysis determined HOMA-IR as an independent contributing factor to CACS.

Conclusions: CAC becomes more prevalent and severe with a decline in GFR, and plasma ADMA levels and insulin resistance, independent of factors associated with CKD-MBD, are correlated with CAC.

Figure 1.

The significant relationship between CACS and GFR is shown (r = 0.218, P < 0.05). When GFR decreases particularly below 60 ml/min per 1.73 m², CACS rapidly increases.

Figure 2.

When CACS was divided into quartiles, the patients with CACS >600 had significantly higher values of log HOMA-IR compared with those in patients with CACS <50 (*P < 0.05). y-axis shows log HOMA values.