The Key Role of Phosphate on Vascular Calcification

Abstract

Vascular calcification (VC) is common in dialysis and non-dialysis chronic kidney disease (CKD) patients, even in the early stage of the disease. For this reason, it can be considered a CKD hallmark. VC contributes to cardiovascular disease (CVD) and increased mortality among CKD patients, although it has not been proven. There are more than one type of VC and every form represents a marker of systemic vascular disease and is associated with a higher prevalence of CVD in CKD patients, as shown by several clinical studies. Major risk factors for VC in CKD include: Increasing age, dialysis vintage, hyperphosphatemia (particularly in the setting of intermittent or persistent hypercalcemia), and a positive net calcium and phosphate balance. Excessive oral calcium intake, including calcium-containing phosphate binders, increases the risk for VC. Moreover, it has been demonstrated that there is less VC progression with non-calcium-containing phosphate binders. Unfortunately, until now, a specific therapy to prevent progression or to facilitate regression of VC has been found, beyond careful attention to calcium and phosphate balance.

Gla-Rich Protein (GRP) as an Early and Novel Marker of Vascular Calcification and Kidney Dysfunction in Diabetic Patients with CKD: A Pilot Cross-Sectional Study

“…Increased levels of serum P, FGF-23 and CaxP, and lower levels of α-Klotho, have all been associated with cardiovascular outcomes in the CKD population [19,36,37]. The association between high serum P levels and CKD is based on the role of phosphate as a primary stimulus for the osteochondrogenic transformation of VSMCs with calcifying capacity [36,38]. The association of GRP with CKD-MBD and VC are consistent with reported data regarding GRP functionality.…”

“…The relationship between bone mineral disorders and VC is well established and a major concern on the management of cardiovascular risk in the CKD population. In this complex interplay, the contribution of phosphate metabolism for VC and cardiovascular outcomes in CKD settings has been widely demonstrated [19,36]. Increased levels of serum P, FGF-23 and CaxP, and lower levels of α-Klotho, have all been associated with cardiovascular outcomes in the CKD population [19,36,37].…”

“…In this complex interplay, the contribution of phosphate metabolism for VC and cardiovascular outcomes in CKD settings has been widely demonstrated [19,36]. Increased levels of serum P, FGF-23 and CaxP, and lower levels of α-Klotho, have all been associated with cardiovascular outcomes in the CKD population [19,36,37]. The association between high serum P levels and CKD is based on the role of phosphate as a primary stimulus for the osteochondrogenic transformation of VSMCs with calcifying capacity [36,38].…”

Vascular Calcification—New Insights into Its Mechanism

“…Increased levels of calcium phosphate products associate with the development of vascular calcification in CKD [59]. Even when renal function is normal, increased phosphate in serum associates with cardiovascular mortality and coronary artery calcification, suggesting that phosphate plays an important role in the pathophysiology of VC [60].…”

Scavenging Intracellular ROS Attenuates p-Cresyl Sulfate-Triggered Osteogenesis through MAPK Signaling Pathway and NF-κB Activation in Human Arterial Smooth Muscle Cells

“…Chronic mineral dysregulation in CKD patients promotes UVC and culminates in premature CV death, even in the early stages of the disease [4][5][6]. Beyond careful attention to disturbances of calcium-phosphate (Ca-P) and vitamin D metabolism, there is an urgent need to explore new therapeutic targets for the intricate mechanism of UVC in clinical practice [7].…”