The Relationship of Fetuin-A with Coronary Calcification, Carotid Atherosclerosis, and Mortality Risk in Non-Dialysis Chronic Kidney Disease

Abstract

Objective: This study investigated the relationship of fetuin-A with coronary calcification, carotid atherosclerosis, and mortality risk in non-dialysis chronic kidney disease (CKD).

Methods: The study included 135 adult patients with CKD at stages 3-5, who were divided into coronary artery calcification (CAC) and non-CAC groups. We excluded current smokers and individuals with diabetes mellitus, inflammatory conditions, liver diseases, acute kidney failure, chronic hemodialysis, and cancer. We conducted kidney function tests, complete blood counts, and measured serum levels of fetuin-A, tumor necrosis factor-alpha (TNF-α), high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), total cholesterol (TC), total triglycerides (TG), high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol. Cardiac spiral computed tomography was used to calculate the CAC score, employing the Agatston method. Carotid ultrasonography was performed to assess carotid intima-media thickness (CIMT) and to detect the presence of plaques.

Results: CAC patients had considerably higher levels of TNF-α (p<0.001), IL-6 (p<0.001), hs-CRP (p=0.006), TC, TG, parathyroid hormone (PTH) (p<0.001) and phosphorus (p<0.001) than non-CAC patients. They also had significantly lower levels of fetuin-A (p<0.001). Fetuin-A was considerably lower in CKD subgroups as CKD progressed. Fetuin-A (p=0.046), age (p=0.009), TNF-α (p=0.027), IL-6 (p=0.005), TG (p=0.002), PTH (p=0.002), and phosphorus (p=0.004) were significant predictors of CAC. CAC and fetuin-A were strong predictors of all-cause mortality and cardiovascular (CV) mortality. Fetuin-A was a significant predictor of CIMT (p=0.045).

Conclusion: Fetuin-A reliably predicted CAC and CIMT. Fetuin-A and CAC emerged as significant risk factors for all-cause and CV mortality in non-dialysis CKD.

Keywords: Atherosclerosis; Dyslipidemia; Hyperparathyroidism; Inflammation.

Fig. 1. Receiver operating characteristic curve showing the accuracy of low levels of serum fetuin-A in predicting coronary artery calcification.

AUC, area under the curve.

Fig. 2. Kaplan Meier showing that patients with CACs ≥400 HU had significantly higher all-cause mortality than those with CACs <400 HU.

CAC, coronary artery calcification; HU, hounsfield units.

Fig. 3. Receiver operating characteristic curve analysis revealing the accuracy of low fetuin-A levels in predicting carotid atherosclerosis

AUC, area under the curve.

Fig. 4. Simple scatter plot showing the correlation of CIMT with fetuin-A.

CIMT, carotid intima-media thickness.