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From bone abnormalities to mineral metabolism dysregulation in autosomal dominant polycystic kidney disease

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Abstract

Autosomal dominant polycystic kidney disease (ADPKD) is the most common monogenic cause of kidney failure. It is a systemic disorder, not only affecting the kidneys, but also associated with cyst formation in other organs such as the liver, spleen, pancreas, and seminal vesicles. Other extra-renal symptoms may consist of intracranial arterial aneurysms, cardiac valvular defects, abdominal and inguinal hernias and colonic diverticulosis. Very little is known regarding bone involvement in ADPKD; however, recent evidence has revealed the potential role of fibroblast growth factor 23 (FGF23). FGF23 is an endocrine fibroblast growth factor acting in the kidney as a phosphaturic hormone and a suppressor of active vitamin D with key effects on the bone/kidney/parathyroid axis, and has been shown to increase in patients with ADPKD, even with normal renal function. The aim of this review is to provide an overview of bone and mineral abnormalities found in experimental models and in patients with ADPKD, and to discuss the possible role of FGF23 in this disease.

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Abbreviations

ADPKD:

Autosomal dominant polycystic kidney disease

[Ca2+]cyt :

Cytosolic Ca2+ concentration

CKD:

Chronic kidney disease

1,25(OH)2D:

1,25-dihydroxyvitamin D

FGF23:

Fibroblast growth factor 23

GFR:

Glomerular filtration rate

PC1:

Polycystin-1

PC2:

Polycystin-2

TmP/GFR:

Tubular maximum for phosphate corrected for the glomerular filtration rate

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Acknowledgements

This work was supported in part by an educational grant from the Research Foundation Flanders (FWO), Belgium. The authors would like to thank Pierre Cochat and Bruno Ranchin (University of Lyon, France), Elena Levtchenko and Pieter Evenepoel (University Hospital of Leuven) and Humbert De Smedt (KU Leuven) for their helpful thoughts and comments.

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Authors and Affiliations

  1. Department of Pediatric Nephrology, University Hospital of Leuven, Herestraat 49, 3000, Leuven, Belgium

    Djalila Mekahli

  2. Laboratory of Molecular and Cellular Signaling, Department of Cellular and Molecular Medicine, KU Leuven, Campus Gasthuisberg O&N I, Leuven, Belgium

    Djalila Mekahli

  3. Centre de Référence des Maladies Rénales Rares, Hôpital Femme Mère Enfant, Hospices Civils de Lyon, Bron, France

    Justine Bacchetta

  4. Université de Lyon, Lyon, France

    Justine Bacchetta

  5. Institut de Génomique Fonctionnelle de Lyon (IGFL), Ecole Normale Supérieure, Lyon, France

    Justine Bacchetta

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Correspondence to Djalila Mekahli.

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Mekahli, D., Bacchetta, J. From bone abnormalities to mineral metabolism dysregulation in autosomal dominant polycystic kidney disease. Pediatr Nephrol 28, 2089–2096 (2013). https://doi.org/10.1007/s00467-012-2384-5

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