<scp>FGF</scp>23 regulates renal sodium handling and blood pressure

Andrukhova, Olena; Slavić, Svetlana; Smorodchenko, Alina; Zeitz, Ute; Shalhoub, Victoria; Lanske, Beate; Pohl, Elena E.; Erben, Reinhold G.

doi:10.1002/emmm.201303716

Cited by 285 publications

(227 citation statements)

References 61 publications

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“…FGF‐23 exerts a direct stimulatory effect on the renin‐angiotensin‐aldosterone system through suppression of angiotensin‐converting enzyme‐2,30 which suggests an alternative mechanism of the negative cardiovascular outcomes associated with FGF‐23. Other mechanisms by which FGF‐23 could lead to adverse cardiovascular consequences include calcitriol deficiency, altered phosphorus homeostasis, systemic inflammation and oxidative stress, and sodium retention 31, 32, 33. Additionally, FGF‐23 may downregulate soluble α‐klotho,34 an enzyme with anti‐aging effects that was shown to protect the heart against cardiac hypertrophy and cardiac remodeling 35, 36.…”

Section: Discussionmentioning

confidence: 99%

Fibroblast Growth Factor‐23 and Heart Failure With Reduced Versus Preserved Ejection Fraction: MESA

Almahmoud

Soliman

Bertoni

et al. 2018

JAHA

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BackgroundHigher fibroblast growth factor‐23 (FGF‐23) levels are associated with incident heart failure (HF) in MESA (the Multiethnic Study of Atherosclerosis). FGF‐23 is also associated with left ventricular hypertrophy. Whether the FGF‐23 association with HF is similar for heart failure with reduced ejection fraction (HFrEF) and heart failure with preserved ejection fraction (HFpEF) is not well established.Methods and ResultsWe studied 6542 participants (mean age 62±10 years, 53% women, mean estimated glomerular filtration rate of 81±18 mL/min per 73 m2) from MESA who were free of cardiovascular disease at baseline (2000–2002). HF events were ascertained by an adjudication committee for a median follow‐up of 12.1 years. We classified HF events as HFrEF (ejection fraction [EF] <50%) or HFpEF [EF] ≥50%) at the time of diagnosis. Cox proportional hazard regression was used to compute hazard ratios and 95% confidence intervals for the association between baseline serum FGF‐23 and incident HFrEF and HFpEF. A total of 134 events were classified as HFpEF, 151 HFrEF, and 49 unknown EF. Following imputation, 149 were classified as HFpEF, 176 HFrEF, and 291 participants had HF (34 participants had HFpEF then HFrEF). In the fully adjusted model, higher FGF‐23 levels were associated with incident HFpEF but not with HFrEF (hazard ratio 1.29, 95% confidence interval, 1.08–1.54) versus (hazard ratio 1.04, 95% confidence interval, 0.84–1.29) for each 20 pg/mL higher serum FGF‐23 concentration.Conclusions FGF‐23 association with HF is driven by the association with HFpEF but not with HFrEF in a population‐based cohort. Further studies are needed to determine the pathological mechanisms mediating this association.

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Section: Discussionmentioning

confidence: 99%

Fibroblast Growth Factor‐23 and Heart Failure With Reduced Versus Preserved Ejection Fraction: MESA

Almahmoud

Soliman

Bertoni

et al. 2018

JAHA

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“…Nonetheless, no significant effects on plasma 1,25(OH) 2 D 3 were observed. FGF23 release could be a compensatory mechanism for the polyuria [53]. The increased urinary phosphate excretion could, at least partially, result from increased FGF23 release.…”

Section: Discussionmentioning

confidence: 99%

Down-Regulation of Renal Klotho Expression by Shiga Toxin 2

Feger¹,

Mia²,

Pakladok³

et al. 2014

Kidney Blood Press Res

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Background/Aims: Shiga toxin 2 may trigger classical hemolytic uremic syndrome (HUS) eventually leading to renal failure. Klotho, a transmembrane protein, protease and hormone mainly expressed in kidney is involved in the regulation of renal phosphate excretion and also retains renal protective effects. Renal failure is associated with renal depletion of klotho. The present study explored the influence of Shiga toxin 2 on renal klotho expression. Methods: Mice were injected with either solvent or Shiga toxin 2 and urinary flow rate and phosphate excretion were determined in metabolic cages. Renal transcript levels were measured by quantitative RT-PCR and renal protein abundance by Western blotting. Plasma concentrations of 1,25(OH)₂D₃ and FGF23 were determined by ELISA and plasma phosphate and urea concentrations by photometry. Results: Shiga toxin 2 treatment was followed by increase of plasma urea concentration, urinary flow rate and renal phosphate excretion but not of plasma phosphate concentration. Shiga toxin 2 treatment strongly decreased klotho mRNA expression and klotho protein abundance in renal tissue. Shiga toxin 2 treatment further increased tumor necrosis factor (TnfE) mRNA levels, as well as protein abundance of phosphorylated p38 MAPK in renal tissue. The treatment significantly increased renal Cyp27b1 and decreased renal Cyp24a1 mRNA levels without significantly altering plasma 1,25(OH)₂D₃ levels. Shiga toxin 2 treatment was further followed by increase of plasma FGF23 concentrations. Conclusion: Shiga toxin 2 treatment stimulated TnfE transcription, down-regulated renal klotho expression and increased FGF23 formation, effects presumably contributing to renal tissue injury. i 2015 S. Karger AG, Basel

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“…FGF23 is a protein secreted primarily by bone tissue (osteoclasts and osteocytes) that regulates phosphate excretion together with parathyroid hormone (PTH), via interaction with FGF receptors. Physiologically, FGF23 requires the presence of co-receptor Klotho to perform its activity at the level of proximal and distal kidney tubules by inhibiting the sodium-phosphate co-transporter mechanism in a modality resembling PTH action, resulting in a phosphaturic effect and in sodium storage that leads to the development of hypervolemia and potentially HTN [36] . A second action of FGF23 to reduce phosphorus levels is to inhibit the synthesis of 1-25 dihydroxide vitamin D or calciferol [OH] 2 D).…”

Section: Fibroblast Growth Factor-23 As a Uremic Toxinmentioning

confidence: 99%

The Cardiovascular Burden in End-Stage Renal Disease

Cozzolino

Galassi

Pivari

et al. 2017

Contributions to Nephrology

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It is well documented that chronic kidney disease patients have an extremely high risk of developing cardiovascular (CV) disease (CVD) compared to the general population. Declining renal function itself represents a continuum of CV risk, and in those individuals who survive to reach end-stage renal disease, the risk of suffering a cardiac event is uncomfortably and unacceptably high. Several pathophysiological pathways have been suggested to account for this, including endothelial dysfunction, dyslipidemia, inflammation, left ventricular hypertrophy, troponins, phosphate, vitamin D, fibroblast growth factor-23, and NT-proBNP. All these conditions and biomarkers may have clear associations with current and subsequent CVD.

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FGF23 regulates renal sodium handling and blood pressure

Cited by 285 publications

References 61 publications

Fibroblast Growth Factor‐23 and Heart Failure With Reduced Versus Preserved Ejection Fraction: MESA

Fibroblast Growth Factor‐23 and Heart Failure With Reduced Versus Preserved Ejection Fraction: MESA

Down-Regulation of Renal Klotho Expression by Shiga Toxin 2

The Cardiovascular Burden in End-Stage Renal Disease

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