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X-linked hypophosphatemia, obesity and arterial hypertension: data from the XLH21 study

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Abstract

Background

The underlying mechanisms of obesity in X-linked hypophosphatemia (XLH) are not known. We aimed to evaluate whether FGF21, an endocrine FGF involved in the regulation of carbohydrate–lipid metabolism, could be involved.

Methods

We performed a prospective multicenter cross-sectional study comparing FGF23, Klotho, and FGF21 levels in teenagers with XLH compared to healthy controls (VITADOS cohort) after matching for age, gender, and puberty. Non-parametric tests were performed (results presented as median (min–max)).

Results

A total of 40 XLH teenagers (n = 20 Standard Of Care, SOC, n = 20 burosumab) were included. While patients receiving burosumab displayed increased BMI as compared to patients receiving SOC, systolic blood pressure expressed as percentile was progressively and significantly lower when comparing the three groups: 77 (4–99) in SOC, 47 (9–98) in burosumab, and 28 (1–94) in controls (p = 0.007). When compared to patients receiving SOC, patients receiving burosumab displayed significantly increased phosphate and 1,25(OH)2D levels. We found increased Klotho levels in patients receiving burosumab. No differences were found for either carbohydrate–lipid biomarkers or FGF21 between the three groups. A total of 21 XLH patients (53%) had insulin resistance (HOMA > 2.4, N = 10 SOC, N = 11 burosumab).

Conclusion

FGF21 does not explain obesity/overweight in XLH. Of note, this study was performed in France in 2018–2019, early after the approval authorizing burosumab only in case of severe XLH despite SOC. As such, the data on systolic blood pressure highlighting a possible impact of burosumab to decrease blood pressure as well as increase Klotho levels deserve further studies given their potential effect on long-term cardiovascular risk.

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Data availability

Datasets analyzed during the current study are not publicly available but are available from the corresponding author on reasonable request.

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Acknowledgements

The authors would like to acknowledge the clinical research associates from the different Reference Centers for their help to conduct this study.

Funding

The Hospices Civils de Lyon received a research grant from Kyowa Kirin for the XLH21 study. An institutional funding for the VITADOS cohort was provided by the Programme Hospitalier de Recherche Clinique Inter-régional (PHRCi 2011, JB). The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

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Authors and Affiliations

  1. Centre de Référence Des Maladies Rares du Calcium Et du Phosphate, Centre de Référence Des Maladies Rénales Rares, Filières Maladies Rares OSCAR, ORKID Et ERK-Net, Hôpital Femme Mère Enfant, Hospices Civils de Lyon, Bron, 69500, France

    Louisa Bloudeau, Sacha Flammier, Aurélia Bertholet-Thomas & Justine Bacchetta

  2. Centre de Référence Des Maladies Rares du Calcium Et du Phosphate, Filière de Santé Maladies Rares OSCAR, Endocrinologie Et Diabète de L’enfant, Hôpital Bicêtre Paris-Saclay, Université Paris Saclay, AP-HP, DMU SEA, INSERM U1185, Paris, 94270, France

    Agnès Linglart, Anna Barosi & Anya Rothenbuhler

  3. Centre d’Investigation Clinique, EPICIME-CIC 1407, Hospices Civils de Lyon, Bron, 69500, France

    Aurélie Portefaix

  4. Centre de Référence Des Maladies Rares du Calcium Et du Phosphate, CHU de Toulouse, Toulouse, 31059, France

    Sanaa Eddiry, Jean-Pierre Salles & Valérie Porquet-Bordes

  5. Service de Biochimie Et Biologie Moléculaire, Hôpital Lyon Sud, Pierre-Bénite, 69310, France

    Christelle Roger

  6. Faculté de Médecine Lyon Est, INSERM, UMR 1033, Université Claude Bernard Lyon1, Lyon, 69008, France

    Christelle Roger & Justine Bacchetta

  7. Faculté de Médecine Lyon Est, Université Claude Bernard Lyon 1, Lyon, 69008, France

    Justine Bacchetta

  8. Néphrologie, Rhumatologie Et Dermatologie Pédiatriques Hôpital Femme Mère Enfant, 59 boulevard Pinel, Bron Cedex, 69677, France

    Justine Bacchetta

Authors
  1. Louisa Bloudeau
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Corresponding author

Correspondence to Justine Bacchetta.

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Conflict of interest

JB and JPS received travel fees and consultant/speaker fees from Kyowa Kirin. JB is an investigator for clinical trials for Kyowa Kirin. AL is an investigator for clinical trials for Kyowa Kirin and her research team receives research grants from Kyowa Kirin.

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Bloudeau, L., Linglart, A., Flammier, S. et al. X-linked hypophosphatemia, obesity and arterial hypertension: data from the XLH21 study. Pediatr Nephrol 38, 697–704 (2023). https://doi.org/10.1007/s00467-022-05636-9

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  • DOI: https://doi.org/10.1007/s00467-022-05636-9

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