Table 2: Open in new tab Main therapies...

		Evidence of efficiency
SNF472	Inhibits crystal formation and growth	↓ VICs mineralization	[162]	Slowed the progression of AV mineralization in HD patients	[163]
		↓ Pig leaflet mineralization	[164]
STS	Chelates precipitated calcium to form soluble calcium thiosulfate	In mice: ↓ Vascular calcifciation ↓ TNF-α, IL-1β, IL-6 in serum and aorta	[165]	Prevented VC in HD patients	[166]
Calcimimetics	Decreases serum PTH and CaxP	↓ PTH in rats, which prevented VECs EndMT, and VC	[74]	Slowed AV calcification in HD patients when given in combination with low-dose vitamin D	[167]
	Promotes PBMCs-induced decalcification	↑ CaSR expression in PBMCs from CKD patients, which rescues their capacity to prevent vascular calcification	[168]
	Activation of CaSR in VICs and monocytes	Deleterious effect: ↑ VICs osteogenic transition and calcification	[56]
		Deleterious effect: ↑ Monocytes/macrophages chemtaxis, infiltration, and inflammation	[169–171]
Phosphate-lowering therapies	Decreases serum phosphorus	In ApoE KO mice with CKD, sevelamer, and lanthanum carbonate reduced valvular atherosclerosis and calcification	[172, 173]	Sevelamer and calcium-based phosphate binder slowed AV and MV calcification in HD patients	[174, 175]
Anti-IL-6	Neutralization of IL-6	Reduces indoxyl-sulfate-induced VICs mineralization	[58]	Subcutaneous administration of ziltivekimab (CKD stages 5–3) or clazakizumab (HD) reduced hsCRP Clazakizumab also reduced phospholipase A2 and lp(a)	[176–178]
HD
HDF, HCO, and MCO dialysis	Improve clearance of uremic retention solute with middle-to-high molecular weight compared to standard high-flux dialysis	↓ Monocyte inflammation ↓ VSMC calcification (MCO/HCO)	[179–182]	Reduce systemic inflammation to a greater extent than conventional high-flux dialysis	[180, 183, 184]
Acetate-free, citrate-acidified bicarbonate dialysis	Reduces serum calcification propensity	Protects against calcium deposition in rat aortic rings cultured ex vivo	[185]	Improves serum calcification propensity, assessed by T50, in HD patients	[186]
Peritoneal dialysis	Greater preservation of residual renal function Improved CKD-MBD More physiological approach to volume removal Reduced valvular shear stress	ND
Vitamin K	Carboxylation of matrix-gla protein	ND	Vit K1 improved vitamin K status and retarded thoracic aortic calcification progress but had no effect on VC in HD patients (Vitavask trial)	[187, 188]

Evidence of efficiency

Treatment

Mechanism of action

Preclinical

Reference

Clinical

Reference

SNF472

Inhibits crystal formation and growth

↓ VICs mineralization

[162]

Slowed the progression of AV mineralization in HD patients

[163]

↓ Pig leaflet mineralization

[164]

STS

Chelates precipitated calcium to form soluble calcium thiosulfate

In mice:
↓ Vascular calcifciation
↓ TNF-α, IL-1β, IL-6 in serum and aorta

[165]

Prevented VC in HD patients

[166]

Calcimimetics

Decreases serum PTH and CaxP

↓ PTH in rats, which prevented VECs EndMT, and VC

[74]

Slowed AV calcification in HD patients when given in combination with low-dose vitamin D

[167]

Promotes PBMCs-induced decalcification

↑ CaSR expression in PBMCs from CKD patients, which rescues their capacity to prevent vascular calcification

[168]

Activation of CaSR in VICs and monocytes

Deleterious effect:
↑ VICs osteogenic transition and calcification

[56]

Deleterious effect:
↑ Monocytes/macrophages chemtaxis, infiltration, and inflammation

[169–171]

Phosphate-lowering therapies

Decreases serum phosphorus

In ApoE KO mice with CKD, sevelamer, and lanthanum carbonate reduced valvular atherosclerosis and calcification

[172, 173]

Sevelamer and calcium-based phosphate binder slowed AV and MV calcification in HD patients

[174, 175]

Anti-IL-6

Neutralization of IL-6

Reduces indoxyl-sulfate-induced VICs mineralization

[58]

Subcutaneous administration of ziltivekimab (CKD stages 5–3) or clazakizumab (HD) reduced hsCRP
Clazakizumab also reduced phospholipase A2 and lp(a)

[176–178]

HDF, HCO, and MCO dialysis

Improve clearance of uremic retention solute with middle-to-high molecular weight compared to standard high-flux dialysis

↓ Monocyte inflammation ↓ VSMC calcification
(MCO/HCO)

[179–182]

Reduce systemic inflammation to a greater extent than conventional high-flux dialysis

[180, 183, 184]

Acetate-free, citrate-acidified bicarbonate dialysis

Reduces serum calcification propensity

Protects against calcium deposition in rat aortic rings cultured ex vivo

[185]

Improves serum calcification propensity, assessed by T50, in HD patients

[186]

Peritoneal dialysis

Greater preservation of residual renal function
Improved CKD-MBD
More physiological approach to volume removal
Reduced valvular shear stress

Vitamin K

Carboxylation of matrix-gla protein

Vit K1 improved vitamin K
status and retarded thoracic aortic calcification progress but had no effect on VC in HD patients (Vitavask trial)

[187, 188]

		Evidence of efficiency
SNF472	Inhibits crystal formation and growth	↓ VICs mineralization	[162]	Slowed the progression of AV mineralization in HD patients	[163]
		↓ Pig leaflet mineralization	[164]
STS	Chelates precipitated calcium to form soluble calcium thiosulfate	In mice: ↓ Vascular calcifciation ↓ TNF-α, IL-1β, IL-6 in serum and aorta	[165]	Prevented VC in HD patients	[166]
Calcimimetics	Decreases serum PTH and CaxP	↓ PTH in rats, which prevented VECs EndMT, and VC	[74]	Slowed AV calcification in HD patients when given in combination with low-dose vitamin D	[167]
	Promotes PBMCs-induced decalcification	↑ CaSR expression in PBMCs from CKD patients, which rescues their capacity to prevent vascular calcification	[168]
	Activation of CaSR in VICs and monocytes	Deleterious effect: ↑ VICs osteogenic transition and calcification	[56]
		Deleterious effect: ↑ Monocytes/macrophages chemtaxis, infiltration, and inflammation	[169–171]
Phosphate-lowering therapies	Decreases serum phosphorus	In ApoE KO mice with CKD, sevelamer, and lanthanum carbonate reduced valvular atherosclerosis and calcification	[172, 173]	Sevelamer and calcium-based phosphate binder slowed AV and MV calcification in HD patients	[174, 175]
Anti-IL-6	Neutralization of IL-6	Reduces indoxyl-sulfate-induced VICs mineralization	[58]	Subcutaneous administration of ziltivekimab (CKD stages 5–3) or clazakizumab (HD) reduced hsCRP Clazakizumab also reduced phospholipase A2 and lp(a)	[176–178]
HD
HDF, HCO, and MCO dialysis	Improve clearance of uremic retention solute with middle-to-high molecular weight compared to standard high-flux dialysis	↓ Monocyte inflammation ↓ VSMC calcification (MCO/HCO)	[179–182]	Reduce systemic inflammation to a greater extent than conventional high-flux dialysis	[180, 183, 184]
Acetate-free, citrate-acidified bicarbonate dialysis	Reduces serum calcification propensity	Protects against calcium deposition in rat aortic rings cultured ex vivo	[185]	Improves serum calcification propensity, assessed by T50, in HD patients	[186]
Peritoneal dialysis	Greater preservation of residual renal function Improved CKD-MBD More physiological approach to volume removal Reduced valvular shear stress	ND
Vitamin K	Carboxylation of matrix-gla protein	ND	Vit K1 improved vitamin K status and retarded thoracic aortic calcification progress but had no effect on VC in HD patients (Vitavask trial)	[187, 188]

Evidence of efficiency

Treatment

Mechanism of action

Preclinical

Reference

Clinical

Reference

SNF472

Inhibits crystal formation and growth

↓ VICs mineralization

[162]

Slowed the progression of AV mineralization in HD patients

[163]

↓ Pig leaflet mineralization

[164]

STS

Chelates precipitated calcium to form soluble calcium thiosulfate

In mice:
↓ Vascular calcifciation
↓ TNF-α, IL-1β, IL-6 in serum and aorta

[165]

Prevented VC in HD patients

[166]

Calcimimetics

Decreases serum PTH and CaxP

↓ PTH in rats, which prevented VECs EndMT, and VC

[74]

Slowed AV calcification in HD patients when given in combination with low-dose vitamin D

[167]

Promotes PBMCs-induced decalcification

↑ CaSR expression in PBMCs from CKD patients, which rescues their capacity to prevent vascular calcification

[168]

Activation of CaSR in VICs and monocytes

Deleterious effect:
↑ VICs osteogenic transition and calcification

[56]

Deleterious effect:
↑ Monocytes/macrophages chemtaxis, infiltration, and inflammation

[169–171]

Phosphate-lowering therapies

Decreases serum phosphorus

In ApoE KO mice with CKD, sevelamer, and lanthanum carbonate reduced valvular atherosclerosis and calcification

[172, 173]

Sevelamer and calcium-based phosphate binder slowed AV and MV calcification in HD patients

[174, 175]

Anti-IL-6

Neutralization of IL-6

Reduces indoxyl-sulfate-induced VICs mineralization

[58]

Subcutaneous administration of ziltivekimab (CKD stages 5–3) or clazakizumab (HD) reduced hsCRP
Clazakizumab also reduced phospholipase A2 and lp(a)

[176–178]

HDF, HCO, and MCO dialysis

Improve clearance of uremic retention solute with middle-to-high molecular weight compared to standard high-flux dialysis

↓ Monocyte inflammation ↓ VSMC calcification
(MCO/HCO)

[179–182]

Reduce systemic inflammation to a greater extent than conventional high-flux dialysis

[180, 183, 184]

Acetate-free, citrate-acidified bicarbonate dialysis

Reduces serum calcification propensity

Protects against calcium deposition in rat aortic rings cultured ex vivo

[185]

Improves serum calcification propensity, assessed by T50, in HD patients

[186]

Peritoneal dialysis

Greater preservation of residual renal function
Improved CKD-MBD
More physiological approach to volume removal
Reduced valvular shear stress

Vitamin K

Carboxylation of matrix-gla protein

Vit K1 improved vitamin K
status and retarded thoracic aortic calcification progress but had no effect on VC in HD patients (Vitavask trial)

[187, 188]

Table 2:

Open in new tab

Main therapies under investigation to prevent VC. ApoE, apolipoprotein E; HDF, hemodiafiltration; ND, not determined.

		Evidence of efficiency
Treatment	Mechanism of action	Preclinical	Reference	Clinical	Reference
SNF472	Inhibits crystal formation and growth	↓ VICs mineralization	[162]	Slowed the progression of AV mineralization in HD patients	[163]
		↓ Pig leaflet mineralization	[164]
STS	Chelates precipitated calcium to form soluble calcium thiosulfate	In mice: ↓ Vascular calcifciation ↓ TNF-α, IL-1β, IL-6 in serum and aorta	[165]	Prevented VC in HD patients	[166]
Calcimimetics	Decreases serum PTH and CaxP	↓ PTH in rats, which prevented VECs EndMT, and VC	[74]	Slowed AV calcification in HD patients when given in combination with low-dose vitamin D	[167]
	Promotes PBMCs-induced decalcification	↑ CaSR expression in PBMCs from CKD patients, which rescues their capacity to prevent vascular calcification	[168]
	Activation of CaSR in VICs and monocytes	Deleterious effect: ↑ VICs osteogenic transition and calcification	[56]
		Deleterious effect: ↑ Monocytes/macrophages chemtaxis, infiltration, and inflammation	[169–171]
Phosphate-lowering therapies	Decreases serum phosphorus	In ApoE KO mice with CKD, sevelamer, and lanthanum carbonate reduced valvular atherosclerosis and calcification	[172, 173]	Sevelamer and calcium-based phosphate binder slowed AV and MV calcification in HD patients	[174, 175]
Anti-IL-6	Neutralization of IL-6	Reduces indoxyl-sulfate-induced VICs mineralization	[58]	Subcutaneous administration of ziltivekimab (CKD stages 5–3) or clazakizumab (HD) reduced hsCRP Clazakizumab also reduced phospholipase A2 and lp(a)	[176–178]
HD
HDF, HCO, and MCO dialysis	Improve clearance of uremic retention solute with middle-to-high molecular weight compared to standard high-flux dialysis	↓ Monocyte inflammation ↓ VSMC calcification (MCO/HCO)	[179–182]	Reduce systemic inflammation to a greater extent than conventional high-flux dialysis	[180, 183, 184]
Acetate-free, citrate-acidified bicarbonate dialysis	Reduces serum calcification propensity	Protects against calcium deposition in rat aortic rings cultured ex vivo	[185]	Improves serum calcification propensity, assessed by T50, in HD patients	[186]
Peritoneal dialysis	Greater preservation of residual renal function Improved CKD-MBD More physiological approach to volume removal Reduced valvular shear stress	ND
Vitamin K	Carboxylation of matrix-gla protein	ND		Vit K1 improved vitamin K status and retarded thoracic aortic calcification progress but had no effect on VC in HD patients (Vitavask trial)	[187, 188]

		Evidence of efficiency
Treatment	Mechanism of action	Preclinical	Reference	Clinical	Reference
SNF472	Inhibits crystal formation and growth	↓ VICs mineralization	[162]	Slowed the progression of AV mineralization in HD patients	[163]
		↓ Pig leaflet mineralization	[164]
STS	Chelates precipitated calcium to form soluble calcium thiosulfate	In mice: ↓ Vascular calcifciation ↓ TNF-α, IL-1β, IL-6 in serum and aorta	[165]	Prevented VC in HD patients	[166]
Calcimimetics	Decreases serum PTH and CaxP	↓ PTH in rats, which prevented VECs EndMT, and VC	[74]	Slowed AV calcification in HD patients when given in combination with low-dose vitamin D	[167]
	Promotes PBMCs-induced decalcification	↑ CaSR expression in PBMCs from CKD patients, which rescues their capacity to prevent vascular calcification	[168]
	Activation of CaSR in VICs and monocytes	Deleterious effect: ↑ VICs osteogenic transition and calcification	[56]
		Deleterious effect: ↑ Monocytes/macrophages chemtaxis, infiltration, and inflammation	[169–171]
Phosphate-lowering therapies	Decreases serum phosphorus	In ApoE KO mice with CKD, sevelamer, and lanthanum carbonate reduced valvular atherosclerosis and calcification	[172, 173]	Sevelamer and calcium-based phosphate binder slowed AV and MV calcification in HD patients	[174, 175]
Anti-IL-6	Neutralization of IL-6	Reduces indoxyl-sulfate-induced VICs mineralization	[58]	Subcutaneous administration of ziltivekimab (CKD stages 5–3) or clazakizumab (HD) reduced hsCRP Clazakizumab also reduced phospholipase A2 and lp(a)	[176–178]
HD
HDF, HCO, and MCO dialysis	Improve clearance of uremic retention solute with middle-to-high molecular weight compared to standard high-flux dialysis	↓ Monocyte inflammation ↓ VSMC calcification (MCO/HCO)	[179–182]	Reduce systemic inflammation to a greater extent than conventional high-flux dialysis	[180, 183, 184]
Acetate-free, citrate-acidified bicarbonate dialysis	Reduces serum calcification propensity	Protects against calcium deposition in rat aortic rings cultured ex vivo	[185]	Improves serum calcification propensity, assessed by T50, in HD patients	[186]
Peritoneal dialysis	Greater preservation of residual renal function Improved CKD-MBD More physiological approach to volume removal Reduced valvular shear stress	ND
Vitamin K	Carboxylation of matrix-gla protein	ND		Vit K1 improved vitamin K status and retarded thoracic aortic calcification progress but had no effect on VC in HD patients (Vitavask trial)	[187, 188]

This Feature Is Available To Subscribers Only