Arterial remodelling in chronic kidney disease: Impact of uraemic toxins and new pharmacological approaches

Abstract

Chronic kidney disease (CKD) is a major public health concern that affects around 10 per-cent of the world’s population. The severity of CKD is mainly due to the high prevalence of cardiovascular (CV) complications in this population. The aim of this review is to describe the arterial remodelling associated with CKD, to provide a quick overview of the mechanisms involved and to review the recent pharmacological approaches aimed at improving vascular health in CKD. CKD patients are exposed to metabolic and haemodynamic disorders that may affect the CV system. Large artery functional and geometric abnormalities have been well documented in CKD patients and are associated with an increase in arterial stiffness and a maladaptive remodelling. Uraemic toxins, such as indoxyl sulphate, p-cresyl sulphate, protein carbamylation and advanced glycation products, exert various effects on vascular smooth muscle cell functions. The low-grade inflammation associated with CKD may also affect arterial wall composition and remodelling. It is worth noting that the CV risk for CKD patients remains high despite the pharmacological control of traditional CV risk factors, suggesting the need for innovative therapeutic strategies. An interventional study targeting the NLRP3 inflammasome has provided some interesting preliminary results that need to be confirmed, especially in terms of safety.