Letters to the Editor Reply to: “Risk Factors for Carotid Artery Disease and Chronic Kidney Disease: Same or Unique?” Carotid Artery Disease and Chronic Kidney Disease—Which Came the First: The Chicken or the Egg?

Dear Editor, We read with great interest the letter by Bosevski et al. (1) and would be willing to address the question: Is carotid artery disease (CARD) a risk factor for chronic kidney disease (CKD), or does CARD interact with other traditional risk factors for prognosis of CKD? CARD, being an atherosclerotic vascular disorder, is one of the common pathways for heart failure and kidney disease. While carotid intima media thickness (CIMT) reflects the focal changes in vascular morphology after the development of atherosclerosis, vascular stiffness reflects the functional properties of carotid arteries and provides information on changes in arteries due to atherosclerosis. Is CARD a risk factor for CKD or can morphological and functional assessments of vascular damage be useful to predict the progression of renal function decline? The Multi-Ethnic Study of Atherosclerosis (MESA) in adults (N = 4878) aged 45–84 years without baseline clinical cardiovascular disease showed that increased CIMT is associated with urine albumin-to-creatinine ratio (UACR) progression. In a general real-life population (N = 611) without known kidney failure, the CIMT mean values and the prevalence of carotid plaques were decreased with increasing tertile of glomerular filtration rate (GFR) (2). However, to the best of our knowledge, whether increased IMT might be a risk factor for declining renal function has not been studied yet. On the other hand, there is an evidence that arterial stiffness different from other parameters of vascular damage may be a risk factor for accelerated renal function decline. This effect was shown to be independent of the conventional risk factors for cardiovascular disease via abnormal central hemodynamics and/or pulsatile nephropathy. Both the kidney and brain are low-resistance, high-flow end organs, which renders them vulnerable to pulsatile changes in the blood flow. This hemodynamic stress on the kidney vasculature may result in an endothelial dysfunction and microvascular ischemia, leading to kidney injury and declining renal function. The analysis of the Rotterdam study has shown that markers of arterial stiffness were independently associated with future decline in kidney function. They observed that the higher pulse pressure and greater carotid stiffness were associated with steeper estimated glomerular filtration rate (eGFR) annual decline and higher-incident CKD risk. A recent report on a Chinese population has shown that arterial stiffness increases the risk of proteinuria, suggesting that it could be considered a target for delaying the CKD development (3). Hence, atherogenic states and renal dysfunction may be components of a vicious cycle, and vascular function abnormalities associated with atherosclerosis may accelerate this cycle. Other possible mechanisms include chronic inflammation, oxidative stress, and the activation of the renin–angiotensin system. In CKD, all mechanisms are accelerated and so may be considered as treatment strategies. A recent systematic review and meta-analysis showed that circulating levels of asymmetric dimethylarginine (ADMA) in CKD patients were positively related to CIMT and would be a predictor of an early-onset atherosclerosis in patients with CKD (4). The combined treatment with ramipril and telmisartan have resulted in the reduction of CIMT and protein thiols (PSH) plasma concentrations, suggesting that the reduction of oxidative stress could have an important role in lowering CIMT levels in CKD. Ang-(1-7), the new member of renin-angiotensin system (RAS), was also considered a new therapeutic option for atherosclerosis that merits further development and exploration. Patients with CKD are exposed to mutual interaction of both traditional and nontraditional risk factors for the disease progression, and thus, therapeutic targeting of both should be considered. Nevertheless, further studies concerning treatment and controlling of these biomarkers and cardiovascular risk in CKD patients, along with the