Recent progress in the treatment of vascular calcification

Abstract

Vascular calcification is common in patients with advanced chronic kidney disease and is associated with poorer outcomes. Although the pathophysiology is not completely understood, it is clear that it is a multifactorial process involving altered mineral metabolism, as well as changes in systemic and local factors that can promote or inhibit vascular calcification, and all of these are potential therapeutic targets. Current therapy is closely linked to strategies for preventing disordered bone and mineral metabolism in advanced kidney disease and involves lowering the circulating levels of both phosphate and calcium. The efficacy of compounds that specifically target calcification, such as bisphosphonates and thiosulfate, has been shown in animals but only in small numbers of humans, and safety remains an issue. Additional therapies, such as pyrophosphate, vitamin K, and lowering of pH, are supported by animal studies, but are yet to be investigated clinically. As the mineral composition of vascular calcifications is the same as in bone, potential effects on bone must be addressed with any therapy for vascular calcification.

Cardiovascular Risk and Mineral Bone Disorder in Patients with Chronic Kidney Disease

“…Atherosclerosis is restricted to large and medium-sized conduit arteries and has been linked mainly to "traditional" risk factors like smoking, obesity, dyslipidaemia, hypertension and aging. By contrast, media calcification can occur in arteries of any size, is a typical age-related process and has been associated with increased stiffness and reduced cushioning function [17,18]. In patients with diabetes mellitus and/or chronic kidney disease, both forms of calcification are present but are usually not distinguished in epidemiological studies, since non-ambiguous discrimination is hardly achievable unless vessel specimens for histological evaluation are available [19].…”

Dietary L-Lysine Prevents Arterial Calcification in Adenine-Induced Uremic Rats

“…[5][6][7][8][9][10] However, satisfactory therapies have not yet been established. 11 Adenine-induced renal failure is one of the commonly used animal models for studying the development of vascular calcification, but the prevalence of vascular calcification in this model is not very high. Indeed, Price et al reported that vascular calcification was detected in only 30% of rats with adenine-induced chronic renal failure (adenine rats) fed a normal-protein diet.…”

Vitamin D and Vascular Calcification in Chronic Kidney Disease

“…The risk of inducing hypercalcemia and hyperphosphatemia with the administration of high doses of calcitriol in CKD patients led to the search for analogs that retain the effect of calcitriol on parathyroid glands while lacking the hypercalcemic and hyperphosphatemic effects [56] . New vitamin D compounds already in clinical use, which have an improved side effect profile, are limited to paricalcitol, 22-oxacalcitriol, and doxercalciferol [57] .…”

“…All the processes involved in the development of vascular calcification, mainly the systemic and local factors that can promote or inhibit vascular calcification, are potential therapeutic targets which are just being evaluated (see O'Neill and Lomashvili [56] for a recent revision).…”