Fibroblast growth factor 23 modifies the pharmacological effects of angiotensin receptor blockade in experimental renal fibrosis

Jong, Maarten A. de; Mirković, Katarina; Mencke, Rik; Hoenderop, Joost G. J.; Bindels, René J. M.; Vervloet, Marc G.; Hillebrands, Jan-Luuk; Born, Jacob van den; Navis, Gerjan; Borst, Martin H. de

doi:10.1093/ndt/gfw105

Cited by 27 publications

(26 citation statements)

References 17 publications

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“…Further renal conditions including fibrosis , albuminuria and autosomal dominant polycystic kidney disease (ADPKD) are associated with elevated FGF23 levels. Also, impaired liver function and lung disease stimulate FGF23 production.…”

Section: Fgf23 Regulation: Insights From Rare Disorders and Renal Dismentioning

confidence: 99%

Regulation of fibroblast growth factor 23 (FGF23) in health and disease

et al. 2019

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Fibroblast growth factor 23 (FGF23) is mainly produced in the bone and, upon secretion, forms a complex with a FGF receptor and coreceptor αKlotho. FGF23 can exert several endocrine functions, such as inhibiting renal phosphate reabsorption and 1,25‐dihydroxyvitamin D3 production. Moreover, it has paracrine activities on several cell types, including neutrophils and hepatocytes. Klotho and Fgf23 deficiencies result in pathologies otherwise encountered in age‐associated diseases, mainly as a result of hyperphosphataemia‐dependent calcification. FGF23 levels are also perturbed in the plasma of patients with several disorders, including kidney or cardiovascular diseases. Here, we review mechanisms controlling FGF23 production and discuss how FGF23 regulation is perturbed in disease.

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Section: Fgf23 Regulation: Insights From Rare Disorders and Renal Dismentioning

confidence: 99%

Regulation of fibroblast growth factor 23 (FGF23) in health and disease

et al. 2019

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“…FGF‐23 blocks the conversion of angiotensin‐II into angiotensin (1–7) . The increase in FGF23 disturbs the renin‐angiotensin aldosterone system (RASS) system and lessens the angiotensin receptor blocker (ARB) efficacy . The activated angiotensin‐II will enhance the production of aldosterone.…”

Section: Traditional Factors Related To the Osteogenic Trans‐differenmentioning

confidence: 99%

“…51 The increase in FGF23 disturbs the renin-angiotensin aldosterone system (RASS) system and lessens the angiotensin receptor blocker (ARB) efficacy. 52 The activated angiotensin-II will enhance the production of aldosterone. Phosphate and calcium stimulate the Na-Pi cotransporter, and aldosterone also contributes to activate the Na-Pi cotransporter, resulting in increased phosphate entrance into VSMC.…”

Section: Traditional Factors Related To the Osteogenic Trans-differenmentioning

confidence: 99%

Mineral bone disorders in chronic kidney disease

Hou

2018

Nephrology

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As the GFR loss aggravates, the disturbed mineral metabolism worsens the bone microstructure and remodelling ‐ scenario, which is known as CKD‐mineral bone disease (MBD). CKD‐MBD is characterized by : (i) abnormal metabolism of calcium, phosphorus, parathyroid hormone (PTH), or vitamin D; (ii) abnormalities in bone turnover, mineralization, volume linear growth or strength; (iii) soft‐tissue calcifications, either vascular or extra‐osseous. Uremic vascular calcification and osteoporosis are the most common complications related to CKD‐MBD. Disregulated bone turnover by uremic toxin or secondary hyperparathyroidism disturbed bone mineralization and makes it difficult for calcium and inorganic phosphate to enter into bone, resulting in increased serum calcium and inorganic phosphate. Vascular calcification worsens by hyperphosphatemia and systemic inflammation. Since vitamin D deficiency plays an important role in renal osteodystrophy, supplement of nutritional vitamin D is important in treating uremic osteoporosis and vascular calcification at the same time. Its pleotropic effect improves the bone remodeling initiated by osteoblast and alleviates the risk factors for vascular calcification with less hypercalcemia than vitamin D receptor analogs. Therefore, nutritional vitamin D should be considered in managing CKDMBD.

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“…Because aldosterone, similar to FGF23, also activates SGK1 in distal renal tubules, FGF23 and aldosterone signaling may have synergistic effects on NCC activation and volume homeostasis. The interaction between FGF23 and the renin-angiotensin-aldosteronesystem (RAAS) has recently been indirectly supported by a study showing that FGF23 treatment interferes with the beneficial effects of angiotensin receptor blockade in mice subjected to unilateral ureteral obstruction as a model of renal fibrosis [73].…”

Section: Distal Tubular Calcium and Sodium Transportmentioning

confidence: 99%

FGF23-Klotho signaling axis in the kidney

Erben

Andrukhova

2017

Bone

125

110

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Fibroblast growth factor-23 (FGF23) is a bone-derived hormone protecting against the potentially deleterious effects of hyperphosphatemia by suppression of phosphate reabsorption and of active vitamin D hormone synthesis in the kidney. The kidney is one of the main target organs of FGF23 signaling. The purpose of this review is to highlight the recent advances in the area of FGF23-Klotho signaling in the kidney. During recent years, it has become clear that FGF23 acts independently on proximal and distal tubular epithelium. In proximal renal tubules, FGF23 suppresses phosphate reabsorption by a Klotho dependent activation of extracellular signal-regulated kinase-1/2 (ERK1/2) and of serum/glucocorticoid-regulated kinase-1 (SGK1), leading to phosphorylation of the scaffolding protein Na/H exchange regulatory cofactor (NHERF)-1 and subsequent internalization and degradation of sodium-phosphate cotransporters. In distal renal tubules, FGF23 augments calcium and sodium reabsorption by increasing the apical membrane expression of the epithelial calcium channel TRPV5 and of the sodium-chloride cotransporter NCC through a Klotho dependent activation of with-no-lysine kinase-4 (WNK4). In proximal and distal renal tubules, FGF receptor-1 is probably the dominant FGF receptor mediating the effects of FGF23 by forming a complex with membrane-bound Klotho in the basolateral membrane. The newly described sodium- and calcium-conserving functions of FGF23 may have major implications for the pathophysiology of diseases characterized by chronically increased circulating FGF23 concentrations such as chronic kidney disease.

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Fibroblast growth factor 23 modifies the pharmacological effects of angiotensin receptor blockade in experimental renal fibrosis

Abstract: Our findings show pharmacological interaction between exogenous FGF23 and losartan, thus serving as a proof of principle for crosstalk between the FGF23-klotho axis and RAAS.

Cited by 27 publications

References 17 publications

Regulation of fibroblast growth factor 23 (FGF23) in health and disease

Regulation of fibroblast growth factor 23 (FGF23) in health and disease

Mineral bone disorders in chronic kidney disease

FGF23-Klotho signaling axis in the kidney

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