Serum Fibroblast Growth Factor-23 Levels and Progression of Aortic Arch Calcification in Non-Diabetic Patients on Chronic Hemodialysis

Tamei, Noriko; Ogawa, Tetsuya; Ishida, Hideyuki; Ando, Yumiko; Nitta, Kosaku

doi:10.5551/jat.5595

Cited by 35 publications

(23 citation statements)

References 34 publications

(23 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In dialysis patients FGF-23 serum concentrations were shown to be clearly associated with vascular calcification and adverse cardiovascular outcome [83,84,85,86,87,88,89,90]. Although these findings are in favor of a causative role of FGF-23 in the development and progression of cardiovascular disease, a recent study on the progression of aortic arch calcification during a 5-year interval in non-diabetic patients on chronic hemodialysis (n=127) revealed an inverse association with the baseline serum concentration of FGF-23 [91]. By contrast, a negative association between FGF-23 serum levels and intensity of peripheral calcification was seen in a rather small cohort of diabetic (n=32) and non-diabetic hemodialysis patients (n=56) [85].…”

Section: Ckd-mbd Effects On the Cardiovascular Systemmentioning

confidence: 99%

Cardiovascular Risk and Mineral Bone Disorder in Patients with Chronic Kidney Disease

Staude

Jeske

Schmitz

et al. 2013

Kidney Blood Press Res

View full text Add to dashboard Cite

The term chronic kidney disease-mineral bone disorder has been coined recently to highlight that the disturbed mineral and bone metabolism is a major contributor to vascular calcification and finally cardiovascular disease. This syndrome is characterized by clinical, biochemical and/or histological findings, i.e. i) biochemical alterations in the homeostasis of calcium, phosphate and their key player parathyroid hormone (PTH), Fibroblast growth factor-23 (FGF-23), klotho and vitamin-D, ii) the occurrence of vascular and/or soft tissue calcification, and iii) an abnormal bone structure and/or turnover. Apart from the combined and synergistic action of "traditional" and uremia-related risk factors, promoters and inhibitors of calcification have to be considered as well. This review will focus on the disturbed mineral metabolism as the triggering force behind distortion of vascular integrity and cardiovascular malfunction in CKD patients.

show abstract

Section: Ckd-mbd Effects On the Cardiovascular Systemmentioning

confidence: 99%

Cardiovascular Risk and Mineral Bone Disorder in Patients with Chronic Kidney Disease

Staude

Jeske

Schmitz

et al. 2013

Kidney Blood Press Res

View full text Add to dashboard Cite

show abstract

“…Interestingly, there was no clear correlation between FGF23 levels and cardiac abnormalities, suggesting that the benefits of sevelamer administration were Vascular Toxicity of Phosphate in CKD calcification and suggested that the excessive accumulation of FGF23 may inhibit the calcification process in hemodialysis patients. 73 Regarding endothelial function, the PIVUS study involving elderly subjects with normal renal function reported an association between circulating levels of FGF23 (within the normal range) on the one hand and impaired endothelium-dependent relaxation, endothelium-independent relaxation and arterial stiffness on the other. 74 Kitagawa et al demonstrated that low serum levels of soluble Klotho are independently associated with vascular stiffness in CKD patients.…”

Section: Animal Studiesmentioning

confidence: 99%

Vascular Toxicity of Phosphate in Chronic Kidney Disease

Gross

Six

Kamel

et al. 2014

Circ J

View full text Add to dashboard Cite

In epidemiological studies of CKD patients and the general population, high phosphate levels are associated with CV disease (CVD). The association is even observed in early-stage CKD and is independent of other traditional CV risk factors. 5, 6 Along with other factors, hyperphosphatemia is involved in the development of vascular calcification (VC) and endothelial dysfunction (ED), 7-9 both of which are major nontraditional CV risk factors for CKD. Phosphate is able to act either directly on these parameters or indirectly via the FGF23/Klotho and PTH axes (Figure 1).We review the various effects of hyperphosphatemia on CV parameters, with a focus on its emerging role in ED. The efficacy of current therapies for improving phosphate-related CV outcomes is also discussed. Direct Effects of Phosphate on CV Calcification and ED Epidemiological and Interventional StudiesVC is deposition of calcium/phosphate, mostly as apatite, in the blood vessels, myocardium and cardiac valves. Calcification of both the intima and media occurs in CKD, 10 resulting in the stiffness of the large arteries (as evidenced by a higher pulse wave velocity) and thus promotion of CV morbidity/ mortality. The results of several epidemiological studies have highlighted an association between serum phosphate levels and VC in stage 5D CKD patients, 11,12 in early-stage CKD patients and in the general population (in whom serum phosphate levels are still within the normal range). 13, 14 Indeed, 2 elegant prospective studies of large cohorts of hosphate, principally provided by food, is involved in many physiological processes: it buffers the intracellular pH, ensures the stability of the skeleton and contributes to many essential biological functions (eg, DNA synthesis, cell membrane phospholipids, energy metabolism and intracellular signaling pathways that are regulated by phosphorylation/dephosphorylation).The physiological concentration of phosphate (0.8-1.5 mmol/L) is tightly regulated by, among others, the fibroblast growth factor 23 (FGF23)/Klotho axis, parathyroid hormone (PTH) and calcitriol (the active form of vitamin D). 1 In chronic kidney disease (CKD), the progressive loss of functional nephrons induces retention of phosphate, which in turn leads to (1) an increase in calcium/phosphate products and (2) FGF23 synthesis. With the aim of preventing hyperphosphatemia, FGF23 decreases circulating levels of calcitriol, thus inhibiting intestinal phosphate and calcium absorption. PTH, the overexpression of which is triggered by hypocalcemia, stimulates bone resorption for the primary purpose of restoring calcemia but in doing so it increases phosphatemia and thus the calcium/phosphate products. During the course of CKD, Klotho's downregulation in both the parathyroid gland and the kidney results in the loss of FGF23 being able to respectively (1) decrease PTH expression and (2) inhibit renal phosphate reabsorption. In late-stage CKD, the few remaining functional nephrons are no longer able to eliminate phosphate and a vicious circle (referred ...

show abstract

“…To the contrary, the second type of VC is located within the medial layer of arterial wall and is linked to factors such as mineral metabolism and uremia-related toxins [11]. Though the majority of available studies [12,13,14,15,16] suggest that the medial calcification may be the predominant type of VC in CKD patients, not all records seem to corroborate this notion. A recent cross-sectional, case-control study of 232 patients on chronic dialysis and 208 age- and sex- matched controls concluded that VC in large conduit arteries is predominantly located in the intima of the arteries and likely connected with atherosclerosis, traditional CV risk factors and inflammation [17].…”

Section: Localization and Risk Factors Of Vcmentioning

confidence: 79%

Physical Activity in Chronic Kidney Disease: a Plausible Approach to Vascular Calcification?

Basile

Lomonte²,

Lisi³

et al. 2014

Kidney Blood Press Res

View full text Add to dashboard Cite

Vascular calcification (VC) is a prominent feature that affects up to 40 to 80% of Chronic Kidney Disease (CKD) patients depending on the degree of renal impairment. Though etiology and pathogenesis of the different types of VC are far from being elucidated, it is conceivable that an imbalance between promoters and inhibitors represents the condition that triggers VC deposition and progression. In addition to traditional cardiovascular risk factors, several lines of evidence suggest that specific factors may affect the arterial system and prognosis in CKD. Over the last decade, a few pharmacological strategies aimed at controlling different selected risk factors for VC have been investigated yielding conflicting results. In light of the complicated interplay between inhibitors and promoters as well as the fact that VC represents the result of cumulative and prolonged exposure to multiple risk factors, a more comprehensive risk modification approach such as lifestyle modification or physical activity (PA) may represent a valid strategy to attenuate VC deposition and progression.We herein aim at reviewing the rationale and current evidence on the potential for lifestyle modification with a specific focus on PA as a cost-effective strategy for VC treatment.

show abstract

Serum Fibroblast Growth Factor-23 Levels and Progression of Aortic Arch Calcification in Non-Diabetic Patients on Chronic Hemodialysis

Cited by 35 publications

References 34 publications

Cardiovascular Risk and Mineral Bone Disorder in Patients with Chronic Kidney Disease

Cardiovascular Risk and Mineral Bone Disorder in Patients with Chronic Kidney Disease

Vascular Toxicity of Phosphate in Chronic Kidney Disease

Physical Activity in Chronic Kidney Disease: a Plausible Approach to Vascular Calcification?

Contact Info

Product

Resources

About