Intact FGF23 and α‐klotho during acute inflammation/sepsis in CKD patients

Dounousi, Evangelia; Torino, Claudia; Pizzini, Patrizia; Cutrupi, Sebastiano; Panuccio, Vincenzo; D’Arrigo, Graziella; ElHafeez, Samar Abd; Tripepi, Giovanni; Mallamaci, Francesca; Zoccali, Carmine

doi:10.1111/eci.12588

Cited by 30 publications

(13 citation statements)

References 37 publications

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“…The DII has been previously validated with several inflammatory markers such as C-reactive protein, interleukin-6, and homocysteine [28][29][30]. Previous studies have suggested that a high DII, which represents a pro-inflammatory diet, may increase the incidence of age-related chronic diseases and all-cause mortality [7,31]. However, to the best of our knowledge, there are no previous studies investigating the association between DII and well-recognized anti-ageing biomarkers such as the S-Klotho protein.…”

Section: Discussionmentioning

confidence: 99%

Dietary Inflammatory Index and S-Klotho Plasma Levels in Middle-Aged Adults

2020

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Background: Soluble Klotho (S-Klotho) is an aging suppressor with a close link with inflammation. However, it is still unknown whether the dietary inflammatory potential is associated with S-Klotho plasma level. We aimed to investigate the association of the Dietary Inflammatory Index (DII) with S-Klotho plasma levels in middle-aged sedentary adults. Methods: 73 middle-aged sedentary adults (40–65 years old) participated in the present study. DII was determined from 28 dietary items obtained by 24 h recalls and food frequency questionnaires. The S-Klotho plasma levels were measured using a solid-phase sandwich enzyme-linked immunosorbent assay. Results: a weak positive association was observed between DII and S-Klotho plasma levels (β = 52.223, R2 = 0.057, p = 0.043), which disappeared after controlling for body mass index (p = 0.057). Conclusions: A pro-inflammatory dietary pattern measured with the DII was slightly and positively associated with S-Klotho plasma levels in middle-aged sedentary adults.

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Section: Discussionmentioning

confidence: 99%

Dietary Inflammatory Index and S-Klotho Plasma Levels in Middle-Aged Adults

2020

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“…These hyperoxaluric rats may have enhanced gene activity, as previously reported in CDDP-induced kidney injury, although it was decreased in the volume depletion model [ 25 ]. In the sepsis model, acute inflammation suppressed FGF23 expression, which in turn upregulated Klotho synthesis [ 9 ]. It is plausible that the elevated Klotho mRNA expression was caused by a lack of negative feedback due to reduced FGF23 or Klotho protein production, and the failure in mRNA translation, such as endoplasmic reticulum (ER) stress induced by ROS and inflammation, inhibited Klotho protein production.…”

Section: Discussionmentioning

confidence: 99%

Changes of Klotho protein and Klotho mRNA expression in a hydroxy-L-proline induced hyperoxaluric rat model

Jaturakan

Buranakarl

Dissayabutra

et al. 2017

The Journal of Veterinary Medical Science

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Klotho protein is recognized as having a renoprotective effect and is used as a biomarker for kidney injury. We investigated the level of Klotho protein in hyperoxaluria-induced kidney injury and the effects of vitamin E (Vit E) and vitamin C (Vit C) supplementation. Hyperoxaluria was induced by feeding 2% (w/v) Hydroxy-L-proline (HLP) in the drinking water for 21 days. Rats were divided into 5 groups; control (Group 1, n=7), HLP treated rats that received nothing else (Group 2, n=7), Vit E (Group 3, n=6), Vit C (Group 4, n=6) and both Vit E and Vit C (Group 5, n=7). Vit E (200 mg/kg) was injected on days 1, 6, 11 and 16, while Vit C (500 mg/kg) was given intravenously on days 1 and 11. The Klotho protein levels and oxidative status were measured. The expression level of kidney Klotho protein expression was significantly reduced by HLP-treatment, while the mRNA expression was higher (P<0.05), the plasma and kidney malondialdehyde and kidney superoxide dismutase activities were increased, and the kidney reduced glutathione and urinary total antioxidant status were decreased (P<0.05). All of these changes were ameliorated by administration of Vit E, Vit C or especially the co-administration of both. In conclusion, HLP-induced hyperoxaluria reduced the kidney Klotho protein level, which could be restored by Vit E and/or Vit C.

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“…Associations between inflammatory markers and FGF23 have been reported in many inflammatory diseases (•56-62). Recently, we and others have shown that inflammatory cytokines are direct regulators of FGF23 production in cardiac fibroblasts (63) and osteoblasts (•24, •25).…”

Section: Inflammation Regulates Fgf23 Production and Cleavagementioning

confidence: 97%

Inflammation regulates fibroblast growth factor 23 production

Francis

David²

2016

Current Opinion in Nephrology and Hypertension

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Purpose of review Fibroblast growth factor 23 (FGF23) is a hormone secreted by osteocytes and osteoblasts that regulates phosphorus and vitamin D homeostasis. FGF23 levels increase progressively in chronic kidney disease (CKD), and FGF23 excess might be a causal factor of left ventricular hypertrophy, CKD progression and death. Therefore, understanding the molecular mechanisms that control FGF23 production is a critical to design therapies to lower FGF23 levels. The present review focuses on the role of inflammatory stimuli on FGF23 regulation and summarizes recent studies that support a novel framework linking inflammation to FGF23 regulation. Recent findings Inflammation and iron deficiency, which are common occurrences in CKD have emerged as novel FGF23 regulators. Recent findings show that inflammation increases FGF23 production in bone through direct and iron-related indirect mechanisms. In these settings, Hypoxia Inducible Factor (HIF)-1α orchestrates FGF23 transcription in response to inflammation and is primarily responsible for coordinating FGF23 production and cleavage. Summary We demonstrate that inflammation increases FGF23 production and may contribute to elevated FGF23 levels in CKD. Osseous HIF-1α may represent a therapeutic target to lower FGF23 levels in CKD patients and minimize the negative consequences associated with FGF23 excess.

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Intact FGF23 and α‐klotho during acute inflammation/sepsis in CKD patients

Cited by 30 publications

References 37 publications

Dietary Inflammatory Index and S-Klotho Plasma Levels in Middle-Aged Adults

Dietary Inflammatory Index and S-Klotho Plasma Levels in Middle-Aged Adults

Changes of Klotho protein and Klotho mRNA expression in a hydroxy-L-proline induced hyperoxaluric rat model

Inflammation regulates fibroblast growth factor 23 production

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