Risk of cardiovascular involvement in pediatric patients with X-linked hypophosphatemia



To find out if cardiovascular alterations are present in pediatric patients with X-linked hypophosphatemia (XLH).

Study design

Multicentre prospective clinical study on pediatric patients included in the RenalTube database (www.renaltube.com) with genetically confirmed diagnosis of XLH by mutations in the PHEX gene. The study’s protocol consisted of biochemical work-up, 24-h ambulatory blood pressure monitoring (ABPM), carotid ultrasonography, and echocardiogram. All patients were on chronic treatment with phosphate supplements and 1-hydroxy vitamin D metabolites.


Twenty-four patients (17 females, from 1 to 17 years of age) were studied. Serum concentrations (X ± SD) of phosphate and intact parathyroid hormone were 2.66 ± 0.60 mg/dl and 58.3 ± 26.8 pg/ml, respectively. Serum fibroblast growth factor 23 (FGF23) concentration was 278.18 ± 294.45 pg/ml (normal < 60 pg/ml). Abnormally high carotid intima media thickness was found in one patient, who was obese and hypertensive as revealed by ABPM, which disclosed arterial hypertension in two other patients. Z scores for echocardiographic interventricular septum end diastole and left ventricular posterior wall end diastole were + 0.77 ± 0.77 and + 0.94 ± 0.86, respectively. Left ventricular mass index (LVMI) was 44.93 ± 19.18 g/m2.7, and four patients, in addition to the obese one, had values greater than 51 g/m2.7, indicative of left ventricular hypertrophy. There was no correlation between these echocardiographic parameters and serum FGF23 concentrations.


XLH pediatric patients receiving conventional treatment have echocardiographic measurements of ventricular mass within normal reference values, but above the mean, and 18% have LVMI suggestive of left ventricular hypertrophy without correlation with serum FGF23 concentrations. This might indicate an increased risk of cardiovascular involvement in XLH.

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Fig. 1


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Serum FGF23 determinations were performed in Dr. Mariano Rodríguez’s laboratory (IMIBIC/Hospital Universitario Reina Sofía, Córdoba, Spain), partly funded by the Funfación Nutrición y Crecimiento.


This study was funded by grants PI12/00987 (National Plan I + D + I 2008–2011) and PI15/02122 (National Plan I + D + I 2013–2016) of the Instituto de Salud Carlos III, by Fondos FEDER, by Fondos Regionales Gobierno del Principado de Asturias (Grupin 14/020), by Foundation of the University of Oviedo (FUO), and funds of University of Oviedo with “Programa de Apoyo y Promoción de la Investigación 2017,” by grant SeveroOcha 2013–2017 of the “Programa Estatal de Promoción del Talento y su Empleabilidad en I + D + I, Subprograma Estatal de Formación” and by Foundation “Nutrición y Crecimiento.”

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Correspondence to Fernando Santos.

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Written inform consent from the participants and approval of the hospital’s ethical committee were obtained.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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The authors declare that they have no conflict of interest.


Poster presentation in the 51st Annual Scientific Meeting of the European Society for Paediatric Nephrology (ESPN), on October 2018 in Belek, Antalya, Turkey.

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Hernández-Frías, O., Gil-Peña, H., Pérez-Roldán, J.M. et al. Risk of cardiovascular involvement in pediatric patients with X-linked hypophosphatemia. Pediatr Nephrol 34, 1077–1086 (2019). https://doi.org/10.1007/s00467-018-4180-3

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  • XLH
  • FGF23
  • Left ventricular hypertrophy
  • PHEX gene
  • Intima-media of carotid artery