Vascular calcification in chronic kidney disease: a review

Oliveira, Rodrigo Bueno de; Okazaki, Hirokazu; Stinghen, Andréa Emília Marques; Drüeke, Tilman B.; Massy, Ziad A.; Jorgetti, Vanda

doi:10.5935/0101-2800.20130024

Cited by 30 publications

(19 citation statements)

References 124 publications

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“…In the CKD population, active inducers of calcification include hypercalcemia, increased levels of parathyroid hormone (PTH), inflammatory cytokines, oxidative stress, uremic toxins, advanced glycation end products, and perhaps most importantly, Pi [20]. A number of these calcification inducers are increased and, simultaneously, active inhibitors are decreased, likely explaining the extremely high prevalence of vascular intimal, medial, and valvular calcification [25–27]. …”

Section: Mechanisms Of Vcmentioning

confidence: 99%

Vascular calcification in CKD-MBD: Roles for phosphate, FGF23, and Klotho

Yamada

Giachelli

2017

Bone

234

177

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Vascular calcification (VC) is highly prevalent in aging, diabetes mellitus, and chronic kidney disease (CKD). VC is a strong predictor of cardiovascular morbidity and mortality in the CKD population. Complex pathological mechanisms are involved in the development of VC, including osteochondrogenic differentiation and apoptosis of vascular smooth muscle cells, instability and release of extracellular vesicles loaded calcium and phosphate, and elastin degradation. Elevated serum phosphate is a late manifestation of CKD, and has been shown to accelerate mineral deposition in both the vessel wall and heart valves. α-Klotho and fibroblast growth factor 23 (FGF23) are emerging factors in CKD-mineral and bone disorder (CKD-MBD) and are thought to be involved in the pathogenesis of uremic VC. There are discordant reports regarding the biomedical effects of FGF23 on VC. In contrast, mounting evidence supports a well-supported protective role for α-Klotho on VC. Further studies are warranted to elucidate potential roles of FGF23 and α-Klotho in VC and to determine where and how they are synthesized in normal and disease conditions. A thorough systemic evaluation of the biomedical interplay of phosphate, FGF23, and α-Klotho may potentially lead to new therapeutic options for patients with CKD-MBD.

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Section: Mechanisms Of Vcmentioning

confidence: 99%

Vascular calcification in CKD-MBD: Roles for phosphate, FGF23, and Klotho

Yamada

Giachelli

2017

Bone

234

177

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“…In fact, CKD is associated with numerous metabolic and endocrine disturbances, including inflammation coupled to abnormalities in calcium and phosphate metabolism, that contribute to this event (Lewis, ; Nitschke & Rutsch, ; Tintut, Patel, Parhami, & Demer, ). Hyperphosphatemia is prelevent in this disease and is caused mainly by hormonal imbalances (De Oliveira et al, ). Elevation in phosphate levels was described to induce medial calcification and VSMC osteogenic differentiation in different in vitro, ex vivo, and in vivo models (Chen et al, ; Giachelli, ; Jono et al, ; Larsson et al, ).…”

Section: Introductionmentioning

confidence: 99%

Characterization and assessment of potential microRNAs involved in phosphate‐induced aortic calcification

Fakhry

Skafi

Fayyad‐Kazan

et al. 2017

Journal Cellular Physiology

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Medial artery calcification, a hallmark of type 2 diabetes mellitus and chronic kidney disease (CKD), is known as an independent risk factor for cardiovascular mortality and morbidity. Hyperphosphatemia associated with CKD is a strong stimulator of vascular calcification but the molecular mechanisms regulating this process remain not fully understood. We showed that calcification was induced after exposing Sprague-Dawley rat aortic explants to high inorganic phosphate level (P , 6 mM) as examined by Alizarin red and Von Kossa staining. This calcification was associated with high Tissue-Nonspecific Alkaline Phosphatase (TNAP) activity, vascular smooth muscle cells de-differentiation, manifested by downregulation of smooth muscle 22 alpha (SM22α) protein expression which was assessed by immunoblot analysis, immunofluorescence, and trans-differentiation into osteo-chondrocyte-like cells revealed by upregulation of Runt related transcription factor 2 (Runx2), TNAP, osteocalcin, and osteopontin mRNA levels which were determined by quantitative real-time PCR. To unravel the possible mechanism(s) involved in this process, microRNA (miR) expression profile, which was assessed using TLDA technique and thereafter confirmed by individual qRT-PCR, revealed differential expression 10 miRs, five at day 3 and 5 at day 6 post P treatment versus control untreated aortas. At day 3, miR-200c, -155, 322 were upregulated and miR-708 and 331 were downregulated. After 6 days of treatment, miR-328, -546, -301a were upregulated while miR-409 and miR-542 were downregulated. Our results indicate that high P levels trigger aortic calcification and modulation of certain miRs. These observations suggest that mechanisms regulating aortic calcification might involve miRs, which warrant further investigations in future studies.

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“…These complications may occur early in the course of CKD and contribute to the development and progression of vascular calcification (VC), an independent, strong predictor of cardiovascular risk that provides incremental prognostic value over traditional risk markers [2].…”

Section: Introductionmentioning

confidence: 99%

Peritoneal Delivery of Sodium Pyrophosphate Blocks the Progression of Pre-existing Vascular Calcification in Uremic Apolipoprotein-E Knockout Mice

et al. 2015

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Chronic kidney disease (CKD) is generally associated with disturbances of mineral and bone metabolism. They contribute to the development of vascular calcification (VC), a strong, independent predictor of cardiovascular risk. Pyrophosphate (PPi), an endogenous inhibitor of hydroxyapatite formation, has been shown to slow the progression of VC in uremic animals. Since in patients with CKD treatment is usually initiated for already existing calcifications, we aimed to compare the efficacy of PPi therapy with that of the phosphate binder sevelamer, using a uremic apolipoprotein-E knockout mouse model with advanced VCs. After CKD creation or sham surgery, 12-week-old female mice were randomized to one sham group and four CKD groups (n = 18-19/group). Treatment was initiated 8 weeks after left nephrectomy allowing prior VC development. Uremic groups received either intraperitoneal PPi (high dose, 1.65 mg/kg or low dose, 0.33 mg/kg per day), oral sevelamer (3 % in diet), or placebo treatment for 8 weeks. Both intima and media calcifications worsened with time in placebo-treated CKD mice, based on both quantitative image analysis and biochemical measurements. Progression of calcification between 8 and 16 weeks was entirely halted by PPi treatment, as it was by sevelamer treatment. PPi did not induce consistent bone histomorphometry changes. Finally, the beneficial vascular action of PPi probably involved mechanisms different from that of sevelamer. Further studies are needed to gain more precise insight into underlying mechanisms and to see whether PPi administration may also be useful in patients with CKD and VC.

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Vascular calcification in chronic kidney disease: a review

Cited by 30 publications

References 124 publications

Vascular calcification in CKD-MBD: Roles for phosphate, FGF23, and Klotho

Vascular calcification in CKD-MBD: Roles for phosphate, FGF23, and Klotho

Characterization and assessment of potential microRNAs involved in phosphate‐induced aortic calcification

Peritoneal Delivery of Sodium Pyrophosphate Blocks the Progression of Pre-existing Vascular Calcification in Uremic Apolipoprotein-E Knockout Mice

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