The relationship between asymptomatic atherosclerosis and hepcidin-25 in chronic kidney disease patients

Abstract

BACKGROUND: The most common and lethal consequence of chronic kidney disease (CKD) is atherosclerotic cardiovascular disease. The persistent inflammation present in CKD increases hepcidin levels. Iron accumulates in the arterial wall in atherosclerosis. Hepcidin-25 was thought to accelerate the development of atherosclerotic plaques by blocking iron release from macrophages. Therefore, we sought to determine the relationship between hepcidin-25 and asymptomatic atherosclerosis in non-dialysis CKD patients. OBJECTIVES: Investigate the relationship between hepcidin-25 and subclinical atherosclerosis in non-dialysis CKD patients. DESIGN: Cross-sectional SETTINGS: Outpatient clinic for urology and nephrology at a university hospital SUBJECTS AND METHODS: Participants above the age of 18 years included a group of healthy controls and a group of CKD patients who were not routinely maintained on hemodialysis. The latter group was further divided according to eGFR into CKD-3, CKD-4 and CKD-5 subgroups. We excluded patients with comorbidities, patients with chronic liver disease, and other conditions or habits. CBC, kidney function tests, and serum levels of hepcidin-25 (SH-25), TNF-α, IL-6, high-sensitivity C-reactive protein (hs-CRP), TC, TG, LDL-C and HDL-C were assessed. To measure carotid intima media thickness (CIMT) and determine presence of plaques, carotid ultrasonography was performed. The near or far walls of common carotid artery, bulb, and internal carotid artery were used to measure CIMT. MAIN OUTCOME MEASURES: SH-25 association and indicators of subclinical atherosclerosis. SAMPLE SIZE: 128 participants, the control group (n=25) and the non-hemodialysis CKD patients (n=103) RESULTS: The CKD patients had significantly higher serum levels of markers of inflammation including IL-6, TNF-α, and hs-CRP ( P <.001 for each) compared to the controls. There was a significantly higher level of TC, TG and LDL-C ( P <.001 for each) and a lower level of HDL-C ( P <.001) in the CDK patients compared to controls. SH-25 was considerably higher in all CKD subgroups, especially with progression of CKD. CIMT was increased in CKD patients especially CKD-4 and CKD-5 subgroups when compared to healthy participants ( P <.001 for each). In the patient group, CIMT showed a positive correlation with SH-25, (r=.65 and P <.001), IL-6 (r=.65, P <.001), TNF-α (r=.71, P <.001), and hs-CRP (r=.52, P <.001). The ROC curve study showed that SH-25 (AUC=.86, P <.001), IL-6 (AUC=.83, P <.001), hs-CRP (AUC=.72, P <.001), TNF-α (AUC=.82, P <.001) were strong predictors of subclinical atherosclerosis in the CKD patients. CONCLUSIONS: SH-25 and CIMT had a positive relationship in CKD patients. The ROC curve showed that SH-25 is a reliable predictor of carotid atherosclerosis. Therefore, we suggest that SH-25 is a vital biomarker of asymptomatic atherosclerosis. LIMITATIONS: Single-center