Targeting a Silent Disease: Vascular Calcification in Chronic Kidney Disease

Abstract

Chronic kidney disease (CKD) patients have a higher risk of developing early cardiovascular disease (CVD). Although vascular calcification (VC) is one of the strongest predictors of CVD risk, its diagnosis among the CKD population remains a serious clinical challenge. This is mainly due to the complexity of VC, which results from various interconnected pathological mechanisms occurring at early stages and at multiples sites, affecting the medial and intimal layers of the vascular tree. Here, we review the most used and recently developed imaging techniques, here referred to as imaging biomarkers, for VC detection and monitoring, while discussing their strengths and limitations considering the specificities of VC in a CKD context. Although imaging biomarkers have a crucial role in the diagnosis of VC, with important insights into CVD risk, circulating biomarkers represent an added value by reflecting the molecular dynamics and mechanisms involved in VC pathophysiological pathways, opening new avenues into the early detection and targeted interventions. We propose that a combined strategy using imaging and circulating biomarkers with a role in multiple VC molecular mechanisms, such as Fetuin-A, Matrix Gla protein, Gla-rich protein and calciprotein particles, should represent high prognostic value for management of CVD risk in the CKD population.

Chronic Kidney Disease with Mineral Bone Disorder and Vascular Calcification: An Overview

“…Various imaging techniques used in clinical contexts can detect VC, computed tomography (CT), vascular and intravascular ultrasound, arteriography, and positron-emitting tomography [ 152 , 153 , 154 ]. However, current techniques cannot differentiate between intimal and medial artery calcification [ 155 ].…”

Apabetalone (RVX-208): A Potential Epigenetic Therapy for the Treatment of Cardiovascular, Renal, Neurological, Viral, and Cancer Disorders

“…From a mechanistic point of view, cardiovascular disease and chronic kidney disease are intrinsically linked partly due to the ability of the latter to contribute to vascular calcification and inflammation, thereby negatively impacting cardiac health. 48,49 Under certain disease states, vascular calcification occurs due to the deposition of calcium phosphate and hydroxyapatite in blood vessels. 50,51 Of importance, BET proteins have been implicated in vascular calcification and stiffness.…”

“…From a mechanistic point of view, cardiovascular disease and chronic kidney disease are intrinsically linked partly due to the ability of the latter to contribute to vascular calcification and inflammation, thereby negatively impacting cardiac health. , Under certain disease states, vascular calcification occurs due to the deposition of calcium phosphate and hydroxyapatite in blood vessels. , Of importance, BET proteins have been implicated in vascular calcification and stiffness . Conversely, a BET inhibitor like apabetalone reduces extracellular calcium deposition and matrix mineralization markers in vascular smooth muscle cells probably by downregulating the mRNA, protein, and enzyme levels of alkaline phosphatase (ALP) .…”

AIF1: Function and Connection with Inflammatory Diseases

“…CKD is a general term for heterogeneous disorders that affect the structure and function of the kidney, and this damage is present for 3 months or more [89]. CKD patients have a higher risk of developing CVD, and vascular calcification (VC) is one of the strongest predictors of CVD risk [90]. Serum aldosterone levels are increased in CKD patients, and mediate the VC process [91,92].…”