Increased Levels of Serum Parathyroid Hormone and Fibroblast Growth Factor-23 Are the Main Factors Associated with the Progression of Vascular Calcification in Long-Hour Hemodialysis Patients

Gadrey, Jean; Bresson, Éric; Lorriaux, Christie; Mayor, Brice; Hurot, Jean-Marc; Deleaval, Patrick; Chazot, Charles

doi:10.1159/000334424

Cited by 45 publications

(37 citation statements)

References 75 publications

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“…High level of iPTH activates bone resorption through enhancing osteoclast formation by increased osteoblastic production of the receptor activator of nuclear factor kappa-B ligand (RANKL), a master regulator of osteoclastogenesis [19]. It results in increased release of serum phosphate and calcium from bone, which also contributed to vascular calcification [20]. This finding was in accordance with our results of the relation between irisin and vascular calcification.…”

Section: Discussionsupporting

confidence: 88%

Lower Serum Irisin Levels Are Associated with Increased Vascular Calcification in Hemodialysis Patients

Lian¹,

He²,

Lata³

et al. 2018

Kidney Blood Press Res

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Background/Aims: Vascular calcification, which involves an active cellular transformation of vascular smooth muscle cells into bone forming cells, is prevalent and predicts mortality in dialysis patients. Its mechanisms are complex and unclear. We presume that irisin, a newly identified myokine also may play roles in vascular calcification in hemodialysis patients. This study aims to evaluate serum irisin levels and establish their relation to vascular calcification and other parameters in hemodialysis patients. Methods: A total of 150 patients on maintenance hemodialysis treatment and 38 age-and sex-matched healthy controls were enrolled in this cross-sectional study. Serum irisin concentrations were measured by ELISA. Vascular calcification was evaluated by abdominal aortic calcification scores. Results: Serum irisin concentrations were significantly lower in hemodialysis patients than in controls [52.8 (22.0, 100.0) vs. 460.8 (434.8, 483.4) ng/ml, P<0.01]. In addition, irisin was negatively correlated with the parathyroid hormone level (P=0.01). The HD patients with vascular calcification showed significantly lower serum irisin concentrations [39.0 (21.7, 86.2) vs.79.0 (39.5, 130.2) ng/mL, P<0.01]. Compared with the group without vascular calcification multivariate logistic regression analyses revealed that serum irisin, HD vintage and age were significant independent determinant factors for vascular calcification in HD patients. Conclusion: Our results are the first to provide a clinical evidence of the association between serum irisin and vascular calcification in HD patients. Lower irisin levels, long-term hemodialysis and old ages are independent risk factors in HD patients.

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Section: Discussionsupporting

confidence: 88%

Lower Serum Irisin Levels Are Associated with Increased Vascular Calcification in Hemodialysis Patients

Lian¹,

He²,

Lata³

et al. 2018

Kidney Blood Press Res

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“…Associations between OPG and mortality among patients without diabetes were independent of inflammation and FGF-23, which is noteworthy because each is an independent risk factor for mortality in patients undergoing dialysis (34)(35)(36). In fact, FGF-23 has been associated with vascular calcification in several studies (37)(38)(39), but not consistently (40), and experimental studies do not support a direct role of FGF-23 in promoting calcification (40,41). Prior associations between FGF-23 and calcification may be in part due to its correlation with phosphate and klotho deficiency.…”

Section: Discussionmentioning

confidence: 91%

Biomarkers of Vascular Calcification and Mortality in Patients with ESRD

Scialla

Kao

Crainiceanu

et al. 2014

Clinical Journal of the American Society of Nephrology

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Background Vascular calcification is common among patients undergoing dialysis and is associated with mortality. Factors such as osteoprotegerin (OPG), osteopontin (OPN), bone morphogenic protein-7 (BMP-7), and fetuin-A are involved in vascular calcification.Design, setting, participants, & measurements OPG, OPN, BMP-7, and fetuin-A were measured in blood samples from 602 incident dialysis patients recruited from United States dialysis centers between 1995 and 1998 as part of the Choices for Healthy Outcomes In Caring for ESRD Study. Their association with all-cause and cardiovascular mortality were assessed using Cox proportional hazards models adjusted for demographic characteristics, comorbidity, serum phosphate, and calcium. An interaction with diabetes was tested because of its known association with vascular calcification. Predictive accuracy of selected biomarkers was explored by C-statistics in nested models with training and validation subcohorts.Results Higher OPG and lower fetuin-A levels were associated with higher mortality over up to 13 years of follow-up (median, 3.4 years). The adjusted hazard ratios (HR) for highest versus lowest tertile were 1.49 (95% confidence interval [95% CI], 1.08 to 2.06) for OPG and 0.69 (95% CI, 0.52 to 0.92) for fetuin-A. In stratified models, the highest tertile of OPG was associated with higher mortality among patients without diabetes (HR, 2.42; 95% CI, 1.35 to 4.34), but not patients with diabetes (HR, 1.26; 95% CI, 0.82 to 1.93; P for interaction=0.001). In terms of cardiovascular mortality, higher fetuin-A was associated with lower risk (HR, 0.85 per 0.1 g/L: 95% CI, 0.75 to 0.96). In patients without diabetes, higher OPG was associated with greater risk (HR for highest versus lowest tertile, 2.91; 95% CI, 1.06 to 7.99), but not in patients with diabetes or overall. OPN and BMP-7 were not independently associated with outcomes overall. The addition of OPG and fetuin-A did not significantly improve predictive accuracy of mortality.Conclusions OPG and fetuin-A may be risk factors for all-cause and cardiovascular mortality in patients undergoing dialysis, but do not improve risk prediction.

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“…PTH functions to maintain normal serum calcium and phosphorus levels, and it too may play a role in vascular calcification. Elevated PTH levels are one of the main factors associated with progression of vascular calcification in hemodialysis patients, and treatment of secondary hyperparathyroidism with calcimimetics prevents progression of calcification and may actually attenuate vascular calcification in this population (47,90,121). In vitro, rats treated with PTH infusions develop significant vascular calcification independently of diet or renal function, which suggests that PTH is a direct or indirect cause of vascular calcification (74).…”

Section: Risk Factors For Vascular Calcification In Ckdmentioning

confidence: 99%

A current understanding of vascular calcification in CKD

Paloian

Giachelli

2014

American Journal of Physiology-Renal Physiology

279

264

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Patients with chronic kidney disease (CKD) and end-stage renal disease (ESRD) have significant cardiovascular morbidity and mortality that is in part due to the development of vascular calcification. Vascular calcification is an active, highly regulated process that shares many similarities with normal bone formation. New discoveries related to extracellular vesicles, microRNAs, and calciprotein particles continue to reveal the mechanisms that are involved in the initiation and progression of vascular calcification in CKD. Further innovations in these fields are critical for the development of biomarkers and therapeutic options for patients with CKD and ESRD.

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Increased Levels of Serum Parathyroid Hormone and Fibroblast Growth Factor-23 Are the Main Factors Associated with the Progression of Vascular Calcification in Long-Hour Hemodialysis Patients

Cited by 45 publications

References 75 publications

Lower Serum Irisin Levels Are Associated with Increased Vascular Calcification in Hemodialysis Patients

Lower Serum Irisin Levels Are Associated with Increased Vascular Calcification in Hemodialysis Patients

Biomarkers of Vascular Calcification and Mortality in Patients with ESRD

A current understanding of vascular calcification in CKD

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