Abstract Background and Aims Atherosclerosis and its associated cardiovascular diseases starting from the early stages of chronic kidney disease (CKD) are the most important cause of increased morbi-mortality in the CKD process. In studies performed in patients with end-stage renal disease (ESRD), it is observed that the calcification occured in the vascular structures was an important component of the atero-arteriolosclerosis process. The number of studies investigating the relationship between vascular calcification and the development of atherosclerosis and increased morbi-mortality in the process of CKD are quite small and limited to patients undergoing hemodialysis (HD) treatment for ESRD. We aimed to investigate the factors affecting the development of atherosclerosis and the role of calcification inhibitors fetuin-A, matrix-Gla protein (MGP), osteoprotegerin (OPG) in atherosclerosis progress. Method Our study was planned to investigate the relationship of serum OPG, MGP and fetuin-A levels with the development of atherosclerosis in the stage 2-3-4-5 chronic kidney patients who did not require dialysis treatment. Thirty-two (17 female, 15 male) healthy individuals and 92 (49 females, 43 males) CKD cases were included. The healthy control group did not have a history of regular use of medication for any reason, known acute or chronic disease. Chronic kidney disease group, with no acute disease, no history of known malignancy and cerebrovascular disease. The patients' GFR was also calculated with CKD-EPI Formula. The mean carotid artery intima media thickness was calculated by dividing the sum of right and left carotid artery intima media thickness. Statistical analysis was performed with IBM SPSS Statistics 20.0.0. Results The laboratory data of the healthy control group, stage 2 CKD group, stage 3 CKD group, stage 4 CKD group and stage 5 CKD groups were statistically compared with the healthy control group, between themselves and the whole CKD group, the results were given in Table-1. Chronic kidney disease group divided into two groups; carotid artery intima media thickness less than 0.750 millimeters (without subclinical atherosclerosis) and those above 0.750 millimeters (with subclinical atherosclerosis). The mean C-IMT, CRP, FETUIN-A, OPG and MGP of the two groups were compared statistically and the results are shown in Table-2. In chronic kidney patients, age (r = 0.493, p <0.001), BMI (r = 0.337, p = 0.001), CRP (r = 0.301, p = 0.004), TG (r = 0.245, p = 0.019 ), urea (r = 0.228, p = 0.029), SBP (r = 0.212, p = 0.043), fasting blood sugar (r = 0.212, p = 0.043) have positive linear relationship, fetuin-A (r = -0.409, P = 0.001), OPG (r = -0.235, p = 0.024), GFR (r = -0.209, p = 0.046) have a negative linear relationship with CIMT. The multiple relationships between CIMT and other variables are given in Table-3. The mean CIMT (r =-0.417, p = 0.001), right CIMT (r = -0.412, p = 0.001), left CIMT (r = -0.410, p = 0.001), urea (r = -353, p = 0.007), CRP (r = -0.322, p = 0.014), UPE (r = -0.301, p = 0.022), creatinine (r = -0.277, p = 0.035), age (r = -0.262, p = 0.047) show a negative linear relationship with Fetuin-A. Multiple relationships between fetuin-A and other variables are given in Table-4. Conclusion Our study shows that; In particular, fetuin-A levels, which is a vascular calcification inhibitor, begin to decline from the early stages of CKD and is significantly lower in patients with atherosclerosis. This suggests that fetuin-A may be used as an early marker in CKD with increased cardiovascular mortality. On the other hand, contradictions related to the levels of OPG and MGP in CKD and its role in the development of atherosclerosis continue. The results in our study also support this situation. Reducing mortality and morbidity in CKD primarily depends on reducing the risk of cardiovascular events. Pre-recognition of these risks is important, so large-scale studies on vascular calcification inhibitors are needed.