Crosstalk between Renal and Vascular Calcium Signaling: The Link between Nephrolithiasis and Vascular Calcification

Abstract

Calcium (Ca2+) is an important mediator of multicellular homeostasis and is involved in several diseases. The interplay among the kidney, bone, intestine, and parathyroid gland in Ca2+ homeostasis is strictly modulated by numerous hormones and signaling pathways. The calcium-sensing receptor (CaSR) is a G protein–coupled receptor, that is expressed in calcitropic tissues such as the parathyroid gland and the kidney, plays a pivotal role in Ca2+ regulation. CaSR is important for renal Ca2+, as a mutation in this receptor leads to hypercalciuria and calcium nephrolithiasis. In addition, CaSR is also widely expressed in the vascular system, including vascular endothelial cells (VECs) and vascular smooth muscle cells (VSMCs) and participates in the process of vascular calcification. Aberrant Ca2+ sensing by the kidney and VSMCs, owing to altered CaSR expression or function, is associated with the formation of nephrolithiasis and vascular calcification. Based on emerging epidemiological evidence, patients with nephrolithiasis have a higher risk of vascular calcification, but the exact mechanism linking the two conditions is unclear. However, a dysregulation in Ca2+ homeostasis and dysfunction in CaSR might be the connection between the two. This review summarizes renal calcium handling and calcium signaling in the vascular system, with a special focus on the link between nephrolithiasis and vascular calcification.

Risks of Carotid Artery Stenosis and Atherosclerotic Cardiovascular Disease in Patients with Calcium Kidney Stone: Assessment of Systemic Inflammatory Biomarkers

“…It is widely acknowledged that kidney stones are associated with several ASCVDs including myocardial infarction, stroke, and vascular calcification [ 12 , 13 ]. Atherosclerotic carotid artery stenosis is an important cause of ischemic stroke and is strongly associated with vascular calcification [ 14 ].…”

The Association between Aortic Calcification Index and Urinary Stones: A Cross-Sectional Study

“…Studies have found that vascular calcification and kidney stones are both related to low serum levels of fetuin-A [ 19 , 20 , 21 ]. In addition, the dysfunction in the calcium-sensing receptor can lead to a dysregulation in renal calcium handling and the failure to prevent vascular calcification [ 22 ]. Furthermore, matrix vesicles, which are the extracellular membrane-bound vesicles and participate in the progression of cardiovascular calcification, could cause nucleation and crystallization, lead to crystal deposition in the renal papilla, and eventually lead to the formation of stones [ 23 ].…”

Vascular Calcification Is Associated with Fetuin-A and Cortical Bone Porosity in Stone Formers

“…SF were divided into two groups according to the mean value of AAC, in order to identify the main differences between groups. Determinants of AAC Score were further investigated using univariable linear regression, which included potentially relevant clinical and/or laboratorial factors for VC (i.e., age, sex [ 47 ], smoking [ 48 ], BMI [ 49 ], renal function, serum levels of Fet-A [ 50 ], sclerostin [ 51 ], ionized calcium [ 50 ], phosphate [ 50 ], PTH, BAP, klotho, FGF23 [ 52 ], 25OH and 1-25OH-vitamin D [ 53 ], blood lipids [ 54 ], urinary calcium, and phosphate [ 50 ]). Subsequently, all variables with a p < 0.05 were included in a multivariable linear regression model to identify independent determinants of AAC score.…”