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Hepatic Production of Fibroblast Growth Factor 23 in Autosomal Dominant Polycystic Kidney Disease

Abstract : Abstract Context The bone-derived hormone fibroblast growth factor (FGF) 23 controls phosphate homeostasis and urinary phosphate excretion. FGF23 plasma levels increase in the early stage of renal insufficiency to prevent hyperphosphatemia. Recent evidence suggests that this increase has effects on cardiac and immune cells that compromise patients’ health. Patients with autosomal dominant polycystic kidney disease (ADPKD) have been reported to have higher FGF23 concentrations than other patients with similar renal function. The significance of this finding has remained unknown. Methods and Results Analyzing the FGF23 plasma levels in 434 patients with ADPKD and 355 control subjects with a measured glomerular filtration rate (mGFR) between 60 and 120 mL/min per 1.73 m2, we confirmed that patients with ADPKD had higher FGF23 plasma concentrations than controls. Remarkably, this difference did not translate into renal phosphate leakage. Using different assays for FGF23, we found that this discrepancy was explained by a predominant increase in the cleaved C-terminal fragment of FGF23, which lacks phosphaturic activity. We found that FGF23 plasma concentration independently correlated with the severity of cystic liver disease in ADPKD. We observed that, in contrast to control liver tissues, the cystic liver from patients with ADPKD markedly expressed FGF23 messenger RNA and protein. In line with this finding, the surgical reduction of polycystic liver mass was associated with a decrease in FGF23 plasma levels independently of any modification in mGFR, phosphate, or iron status. Conclusion Our findings demonstrate that severely polycystic livers produce FGF23 and increase levels of circulating FGF23 in patients with ADPKD.
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https://hal-u-picardie.archives-ouvertes.fr/hal-03815054
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Soumis le : vendredi 14 octobre 2022 - 12:46:54
Dernière modification le : samedi 15 octobre 2022 - 03:10:46

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Frank Bienaimé, Ariane Ambolet, Béatrice Aussilhou, François Brazier, Marie Fouchard, et al.. Hepatic Production of Fibroblast Growth Factor 23 in Autosomal Dominant Polycystic Kidney Disease. Journal of Clinical Endocrinology and Metabolism, 2018, 103 (6), pp.2319-2328. ⟨10.1210/jc.2018-00123⟩. ⟨hal-03815054⟩

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