Bone-Vascular Axis in Chronic Kidney Disease

Evenepoel, Pieter; Opdebeeck, Britt; David, Karel; D’Haese, Patrick C.

doi:10.1053/j.ackd.2019.09.006

Cited by 58 publications

(46 citation statements)

References 168 publications

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“…( 35 ) Our group and others suggested that sclerostin could be the signaling molecule in the VC‐bone axis because it is highly expressed in calcified vessels and as such could potentially be secreted into circulation. ( 24,39,48 ) Our model of CKD‐induced VC was accompanied by a large increase in plasma sclerostin, which was not reflected in the uremic rat's bone's expression of sclerostin as its mRNA levels were significantly lower to normal controls. The ex vivo cultures of aorta demonstrated a high secretion of sclerostin from the calcified aorta.…”

Section: Discussionmentioning

confidence: 89%

Chronic Kidney Disease–Induced Vascular Calcification Impairs Bone Metabolism

Mace

Gravesen

Nordholm

et al. 2020

Journal of Bone and Mineral Research

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An association between lower bone mineral density (BMD) and presence of vascular calcification (VC) has been reported in several studies. Chronic kidney disease (CKD) causes detrimental disturbances in the mineral balance, bone turnover, and development of severe VC. Our group has previously demonstrated expression of Wnt inhibitors in calcified arteries of CKD rats. Therefore, we hypothesized that the CKD‐induced VC via this pathway signals to bone and induces bone loss. To address this novel hypothesis, we developed a new animal model using isogenic aorta transplantation (ATx). Severely calcified aortas from uremic rats were transplanted into healthy rats (uremic ATx). Transplantation of normal aortas into healthy rats (normal ATx) and age‐matched rats (control) served as control groups. Trabecular tissue mineral density, as measured by μCT, was significantly lower in uremic ATx rats compared with both control groups. Uremic ATx rats showed a significant upregulation of the mineralization inhibitors osteopontin and progressive ankylosis protein homolog in bone. In addition, we found significant changes in bone mRNA levels of several genes related to extracellular matrix, bone turnover, and Wnt signaling in uremic ATx rats, with no difference between normal ATx and control. The bone histomorphometry analysis showed significant lower osteoid area in uremic ATx compared with normal ATx along with a trend toward fewer osteoblasts as well as more osteoclasts in the erosion lacunae. Uremic ATx and normal ATx had similar trabecular number and thickness. The bone formation rate did not differ between the three groups. Plasma biochemistry, including sclerostin, kidney, and mineral parameters, were similar between all three groups. ex vivo cultures of aorta from uremic rats showed high secretion of the Wnt inhibitor sclerostin. In conclusion, the presence of VC lowers BMD, impairs bone metabolism, and affects several pathways in bone. The present results prove the existence of a vasculature to bone tissue cross‐talk. © 2020 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

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Section: Discussionmentioning

confidence: 89%

Chronic Kidney Disease–Induced Vascular Calcification Impairs Bone Metabolism

Mace

Gravesen

Nordholm

et al. 2020

Journal of Bone and Mineral Research

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“…Previous studies have shown an association between VC and low bone mineral density (BMD) or bone mass in CKD patients [6,7,22]. Osteoporosis and VC are closely related because they share pathogenic factors, such as inflammation and vitamin D, vitamin K, and Klotho deficiencies [23]. Renal osteodystrophy, which is the bone component of CKD-MBD, affects bone quality as well as bone quantity [24].…”

Section: Discussionmentioning

confidence: 99%

Sex-specific relationship between vascular calcification and incident fracture in patients with end-stage renal disease

Nam

Hwang

Kim

et al. 2020

Kidney Res Clin Pract

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Chronic kidney disease-mineral and bone disorder (CKD-MBD) is a clinical syndrome that describes a systemic disorder of mineral and bone metabolism caused by CKD. CKD-MBD includes biochemical abnormalities of calcium, phosphorus, parathyroid hormone (PTH), and vitamin D, bone disease, and vascular calcification (VC) [1]. The incidence of fracture increases as CKD progresses [2]. In the Dialysis Outcomes and Practice Patterns Study (DOPPS), across all countries studied the incidence of fracture was significantly higher in patients receiving maintenance dialysis compared with the gen

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“…Most patients with CKD 3 to 5 stages show an increased serum parathyroid hormone level [6]. In CKD-mineral and bone disorders, circulating factors released from vessels may affect bone metabolism, while the bone disease may increase vascular calcification, highlighting the mortality risk [6,7].…”

Section: Introductionmentioning

confidence: 99%

Dietary Patterns and Progression of Impaired Kidney Function in Japanese Adults: A Longitudinal Analysis for the Fukushima Health Management Survey, 2011–2015

Ohira

Yasumura

et al. 2021

Nutrients

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To investigate associations between dietary patterns and the risk of impaired kidney function, we analyzed data from 14,732 participants (40–89 years) who completed the baseline diet questionnaire of The Fukushima Health Management Survey in 2011. The incidence of chronic kidney disease (CKD) (estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 or proteinuria (≥1+ by dipstick test)) and annual changes in eGFR were assessed from 2012 to 2015. Three major dietary patterns were identified. The adjusted cumulative incidence ratio of the highest vs. lowest tertile of a vegetable diet scores was 0.90 (95% confidence interval (CI): 0.82, 1.00) for eGFR < 60 mL/min/1.73 m2, 0.68 (95% CI: 0.52, 0.90) for proteinuria, and 0.88 (95% CI: 0.80, 0.97) for CKD (P for trend = 0.031, 0.007, and 0.005, respectively). The incident risk of CKD in the highest tertile of juice diet scores was 18% higher than the lowest tertile. The odds ratio of the highest vs. lowest tertile of vegetable diet scores was 0.85 (95% CI: 0.75, 0.98) in the rapidly decreasing eGFR group (P for trend = 0.009). We did not observe significant associations for the meat dietary pattern. A Japanese vegetable diet could reduce the risk of developing impaired kidney function and CKD.

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Bone-Vascular Axis in Chronic Kidney Disease

Cited by 58 publications

References 168 publications

Chronic Kidney Disease–Induced Vascular Calcification Impairs Bone Metabolism

Chronic Kidney Disease–Induced Vascular Calcification Impairs Bone Metabolism

Sex-specific relationship between vascular calcification and incident fracture in patients with end-stage renal disease

Dietary Patterns and Progression of Impaired Kidney Function in Japanese Adults: A Longitudinal Analysis for the Fukushima Health Management Survey, 2011–2015

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