Targeting a Silent Disease: Vascular Calcification in Chronic Kidney Disease
Abstract
:1. Introduction
2. Vascular Calcification and Cardiovascular Clinical Outcomes
3. Imaging Cardiovascular Calcification in CKD Patients
3.1. Radiology Techniques
3.2. Ultrasonography Techniques
3.3. Molecular Imaging Techniques
4. Circulating Biomarkers of Vascular Calcification in CKD
4.1. Fetuin-A, Matrix Gla Protein and Gla Rich Protein in Vascular Calcification in CKD: Potential Biomarker Utility
4.2. Calciprotein Particles (CPPs) as a Potential Biomarker of Vascular Calcification Progression in CKD
CPP-Fetuin-A and T50 Calcification and Tests
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Clinical Assessment | Anatomical Sites | Population | VC Scores | Refs. |
---|---|---|---|---|
X-Ray Techniques | ||||
Plain X-ray | Hands, pelvis, femur | Hemodialysis patients | Adragão Score | [28,29] |
Lateral Dual-energy X-ray Absorptiometry | Abdominal aorta artery | Dialysis patients | Kauppila Score | [30,31] |
Ultrasonography Techniques | ||||
Duplex Ultrasound | Common femoral artery, proximal and distal superficial femoral artery and popliteal artery | Peripheral arterial disease patients | DULLAC Score | [32] |
Echocardiography | Aortic valve Mitral annular and aortic root | Coronary disease patients | THC Score | [33] |
Transthoracic Echocardiography | Coronary arteries | Coronary disease patients | Echo Score | [34] |
B-mode Doopler Ultrasound | Carotid arteries, abdominal aorta and lower limbs vessels | Low-intermediate cardiovascular risk patients | CALC Score | [35] |
Intravascular Ultrasound | Coronary arteries | Coronary disease patients | IVUS Calcium Score | [36] |
Molecular Imaging Techniques | ||||
Electron Beam or Multislice Computed Tomography | Coronary arteries | CKD patients | Agatston Score | [37] |
Coronary arteries | Asymptomatic patients | Agatston Score | [38,39,40] | |
Coronary arteries | Coronary artery disease patients | Agatston Score | [41] | |
Thoracic aorta | Peritoneal dialysis patients | Agatston Score | [38] | |
Abdominal aorta | Asymptomatic patients | Agatston Score | [40] | |
Mitral and aortic valve | CKD | Agatston Score | [42] | |
Coronary arteries | Coronary calcification patients | Volume Score | [43] | |
Coronary arteries | Asymptomatic patients | Mass Score | [44] |
Promoters | Role in Vascular Calcification | Inhibitors | Role in Vascular Calcification |
---|---|---|---|
FGF-23 [80] | Hormone that functions as a central endocrine factor that regulates phosphate balance by modulating phosphate reabsorption in the kidney, parathyroid hormone (PTH) secretion and vitamin D metabolism. | Fetuin-A [84] | Binds directly to calcium and phosphate forming mineral complexes (Calciprotein Particles). It represses growth of crystal and mineral deposition. |
OC [85] | Vitamin K-dependent protein (VKDP) secreted by osteoblasts functioning as a negative regulator of bone formation, regulator of mineral maturation rate and mechanical stabilizer of bone matrix; regulator of glucose metabolism. | MGP [86] | VKDP functioning as an inhibitor of soft tissue calcification involved in the VSMCs phenotypic differentiation, binding to calcium and calcium-phosphate circulating forms, thereby preventing its growth and matrix deposition. |
Phosphate [87] | Promotes VSMC differentiation and apoptosis; elevates FGF-23; decreases Klotho expression; clusters with calcium in mineral complexes and promotes matrix mineralization. | GRP [46] | VKDP functioning as an inhibitor of soft tissue calcification involved in the VSMCs phenotypic differentiation and mineralization competence of extracellular vesicles; inhibitor of mineral crystal maturation and growth in blood; anti-inflammatory agent. |
Calcium [88] | Clusters with phosphate in mineral complexes and promotes matrix mineralization; influences parathyroid hormone and Vitamin D production stimulus affecting FGF-23 levels. | OPN [89] | Prevents calcium crystal growth and accelerates osteoclast function. |
OPG [90] | Binds to the RANKL, thereby interfering with RANK-RANKL axis. Inhibition of RANKL-RANK inhibits the differentiation of osteoclast maturation, and thus, bone resorption. | ||
α-Klotho [79] | Klotho decreases kidney phosphate reabsorption by acting as a coreceptor for FGF23. Reduced levels are associated with cell senescence, cell apoptosis, oxidation induced cell damage and lower autophagy activity. | ||
Vitamin K [91] | Is the co-factor of γ-glutamyl carboxylase enzyme, responsible for the y-carboxylation of VKDPs. |
Clinical Markers | Population | VC Detection Method | Evidence of VC Marker and Score Association | Refs. |
---|---|---|---|---|
Phosphate | CKD | CAC | Yes | [97] |
Nondialysis CKD | Kauppila and Adragão | Yes | [98] | |
Nondialysis CKD | Kauppila and Adragão | No | [99] | |
GF23 | CKD | Adragão | Yes | [46] |
Hemodialysis | CAC-Agatston | Yes | [100] | |
Hemodialysis | Echocardiography | No | [89] | |
Hemodialysis | CAC-Agatston | Yes | [101] | |
α-Klotho | Hemodialysis | CAC | Yes | [102] |
OPN | Hemodialysis | Echocardiography | Yes | [89] |
OC | Hemodialysis | Transthoracic Echocardiography | No | [103] |
OPG | Hemodialysis | CAC-Agatston | Yes | [90] |
Hemodialysis | CAC-Agatston | Yes | [100] | |
Vitamin K status/ dp-ucMGP | Hemodialysis | CAC-Agatston | No | [104] |
CKD | CAC-Agatston | No | [105] | |
Hemodialysis | CAC-Agatston | No | [106] | |
CKD | CAC | Yes | [86,107] | |
Hemodialysis | Kauppila | Yes | [108] | |
Hemodialysis | CAC-Agatston | No | [100] | |
GRP | CKD | Adragão | Yes | [46] |
CVD | CAC | No | [109] | |
CKD | Ultrasound | Yes | [110] | |
CKD | Echocardiography | Yes | [111] | |
Fetuin-A | Renal Transplant | CAC | Yes | [112] |
ESRD | CAC | No | [113] | |
CKD | CAC | Yes | [84] |
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Marreiros, C.; Viegas, C.; Simes, D. Targeting a Silent Disease: Vascular Calcification in Chronic Kidney Disease. Int. J. Mol. Sci. 2022, 23, 16114. https://doi.org/10.3390/ijms232416114
Marreiros C, Viegas C, Simes D. Targeting a Silent Disease: Vascular Calcification in Chronic Kidney Disease. International Journal of Molecular Sciences. 2022; 23(24):16114. https://doi.org/10.3390/ijms232416114
Chicago/Turabian StyleMarreiros, Catarina, Carla Viegas, and Dina Simes. 2022. "Targeting a Silent Disease: Vascular Calcification in Chronic Kidney Disease" International Journal of Molecular Sciences 23, no. 24: 16114. https://doi.org/10.3390/ijms232416114