X-linked hypophosphatemia (XLH) is diagnosed in children with clinical and or radiological signs of rickets, impaired growth velocity, low serum phosphate levels associated with renal phosphate wasting, in the absence of vitamin D or calcium deficiency. Conventional treatment is made of phosphate and active vitamin D. However, nephrocalcinosis has been identified as a complication of this therapy. Its prevalence is about 25-40% in adult XLH treated patients. It was never characterized in large cohorts of XLH children. The purpose of our study was to evaluate the prevalence of nephrocalcinosis and identify risk factors associated to the occurrence of this complication.
Methods: We studied 117 children with XLH (74 girls and 43 boys) ranging in age from 6 months to 18 years (median 9.4). The diagnosis of nephrocalcinosis was established by systematic renal ultrasound. The evaluation was recorded at the 1st identification of nephrocalcinosis or, for patients without nephrocalcinosis, at the last available ultrasound. Kidney function was assessed through creatinine clearance. Potential risks factors included markers of clinical disease severity, i.e. short stature, lower limb deformities, dental abscesses, craniosynostosis, chiari malformation, bone fracture, bone surgery and deafness, markers of biochemical imbalanceand treatment follow up i.e. observance, duration of treatment, mean dose of treatment during the last four years preceeding the diagnosis of nephrocalcinosis or the last visit.
Results: 47 of the 117 patients (40.2%) developed nephrocalcinosis after 6.6±3.8 years of conventional treatment. All patients had a normal renal function. Patients with nephrocalcinosis had been exposed to dose of phosphate supplements significantly higher at the time of nephrocalcinosis diagnosis than patients without nephrocalcinosis at their last visit, i.e. 44.2±14.7 mg/kg/day versus 36.1±9.7 mg/kg/day, P=0.001, respectively. Similarly, the mean dose of phosphate administered during 4 years prior to the study evaluation was significantly higher in patients with nephrocalcinosis than in patients without, i.e 49.9±20.5 mg/kg/day vs 42.2±11.4 mg/kg/day, P=0.012, respectively. Patients with nephrocalcinosis displayed a better observance than patient without 84.8 % vs 64.7 % (P= 0.02). Patients with nephrocalcinosis presented with markers of severe disease. In fact the prevalence of craniosynostosis 23.3 % vs 8.3 % (P = 0.047), chiari malformation 27.9 % vs 17.2 %, dental abscesses 50 % vs 34.8 % was higher in this group.
Conclusion: Nephrocalcinosis is a frequent complication of the conventional treatment. It is associated with higher doses of therapy which could be explained by the severity of the disease.
19 - 21 Sep 2019
European Society for Paediatric Endocrinology