Hepatic production of fibroblast growth factor 23 in autosomal dominant polycystic kidney disease.

Hepatic production of fibroblast growth factor 23 in autosomal dominant polycystic kidney disease.

J Clin Endocrinol Metab. 2018 Mar 29;:

Authors: Bienaimé F, Ambolet A, Aussilhou B, Brazier F, Fouchard M, Viau A, Barre P, Tissier AM, Correas JM, Paradis V, Terzi F, Friedlander G, Knebelmann B, Joly D, Prié D

Abstract
Context: the bone-derived hormone fibroblast growth factor 23 (FGF23) controls phosphate homeostasis and urinary phosphate excretion. FGF23 plasma levels increase at the early step of renal insufficiency to prevent hyperphosphatemia. Recent evidence suggests that this increase has off-target effects on cardiac and immune cells that compromises patients' health. Subjects with autosomal dominant polycystic kidney disease (ADPKD) have been reported to display higher FGF23 concentrations than non-ADPKD patients with similar renal function. The significance of this intriguing finding has remained obscure so far.
Methods and results: analysing the FGF23 plasma level in 434 ADPKD patients and 355 control subjects with a measured glomerular filtration rate (mGFR) between 60-120 ml/min/1.73m2, we confirmed that ADPKD patients display higher FGF23 plasma concentrations than controls. Remarkably, this increase 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 is devoid of phosphaturic activity. We found that the FGF23 plasma concentration independently correlated with the severity of cystic liver disease in ADPKD. We observed that, contrary to control liver tissues, the cystic liver from ADPKD patients markedly expresses FGF23 mRNA 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 contribute to the elevation of circulating FGF23 level in ADPKD patients.

PMID: 29618028 [PubMed - as supplied by publisher]

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