Cardiovascular events in chronic kidney disease (CKD)—an importance of vascular calcification and microcirculatory impairment

Abstract

In patients with chronic kidney disease (CKD), particularly in patients with hemodialysis, cardiovascular mortality rate is extremely high. Polyvascular diseases develop at an early stage of CKD. Pathophysiology includes insulin resistance and/or imbalance between nitric oxide (NO) and endothelin bioavailability as well as oxidative stress. Overlooked pathophysiology may be hemorheological disarrangement because of hyperfibrinogenemia, and higher rate of production for monocyte-platelet complexes in circulation, which plays an important role for atherosclerosis. In terms of clinical findings, most of nephrologists have already known about the importance of coronary artery disease, while few of nephrologists are aware of devastating influence of peripheral arterial disease (PAD) on prognosis for the patients with CKD which is known to be one of the independent risk factors for PAD. The understanding in pathophysiology of vascular calcification and strategic treatment is a critical issue to achieve favorable outcome for the patients with CKD. In this regard, FGF-23 and associated factors together with Klotho molecules play an important role. In this article, we aim to review the cardiovascular disease for the patients with CKD with a particular emphasis on the clinical aspects of polyvascular disease. Finally, we address to detect microcirculatory impairment and eradicate vascular calcification as early as possible prior to renal replacement therapy. Apparently, FGF-23-Klotho gene axis as well as vitamin D and phosphate control should be investigated vigorously.

Impact of vascular calcification on cardiovascular mortality in hemodialysis patients: clinical significance, mechanisms and possible strategies for treatment

“…As mentioned in a recent review [1], active atherosclerotic process has already begun in the early stages of chronic kidney disease (CKD), and atherosclerotic organ damages deteriorate along with the decreasing renal function. By the time of the initiation of renal replacement therapy (RRT), major atherosclerotic vascular damages have already been completed in many patients.…”

Cardiovascular Events in Hemodialysis Patients: Challenging against Vascular Calcification

“…However, prior to this finding, there is an increase in the parathyroid hormone (PTH) level and a decrease in the active vitamin D3 level. Recently, the timing and pathogenesis of inflammation have been clarified 6 ) : before the above changes, there is an increase in the FGF-23 level and a reduction in the expression of Klotho gene, which will be examined as an important factor in the future. Such a pathogenesis, including acidemia, other than classical risk factors, such as blood pressure and dyslipidemia, must be carefully evaluated in the process of pre-dialysis kidney disease progression and managed in the early stage.…”

Association between zinc deficiency and aorta stiffness in non-diabetic hemodialysis patients

“…Recent reports indicate that zinc plays an important role in suppressing the calcification of vascular smooth muscle [11,12]. Vascular calcification is serious problem, leading to poor prognosis in terms of cardiovascular events, particularly in patients with chronic kidney disease [13,14]. However, to our knowledge, there are no reports on the association between zinc and aorta stiffness in dialysis patients.…”