Funding outcome

Objectives X-linked hypophosphatemia (XLH) is the most common cause of genetic hypophosphatemia and is caused by a PHEX mutation that leads to elevated fibroblast growth factor 23. XLH has multisystemic comorbidities in children that are not well understood, including high rates of hypertension (HTN). HTN is postulated to be due to hyperparathyroidism or nephrocalcinosis, but evidence is limited by small sample size and outdated HTN criteria. The aim of our study was to determine rates of HTN in children with XLH and associated risk factors. Methods We performed a retrospective chart review of children (<17 years of age) with XLH followed at two tertiary care centers, the Stollery Children's Hospital in Alberta, Canada and the Children's Hospital of Los Angeles in the United States from 2014-2022. HTN was determined by criteria published in the Fourth Report on the Diagnosis, Evaluation, and Treatment of High Blood Pressure in Children and Adolescents. Clinical data was collected, including blood pressure (BP), biochemistry, treatment dosing and renal ultrasound results. Descriptive statistical analyses, unpaired t-tests and/or Chi-squared tests were performed to compare frequency of nephrocalcinosis, PTH levels and use of conventional therapy vs burosumab in hypertensive and normotensive children (IBM SPSS Statistics 28.0.1, 2021, Chicago). Results We evaluated 46 pediatric patients (mean age 11.6 ± 4.2 years, 63% female) with XLH. Sixteen children (16/46, 35%) had stage 1 HTN (mean age 11.3 ± 3.7 years, 53% female). Two children with HTN had nephrocalcinosis (2/16, 13%), which was observed less frequently in children with HTN compared to normotensive children (p=0.01). Parathyroid hormone levels also did not differ significantly between groups (mean 6.8 vs 7.2 pmol/L; p=0.54). Treatment was conventional therapy (62%) and burosumab (38%). Patients that switched from conventional to burosumab treatment during the study period experienced a significant reduction in mean systolic BP (82nd vs 63rd BP percentile; p=0.04). Conclusions Children with XLH have high rates of hypertension. Contrary to previous publications, we did not find elevated PTH or higher rates of nephrocalcinosis in hypertensive patients. Fibroblast growth factor 23 has been associated with vascular morbidity in chronic kidney disease and interestingly, children on anti-fibroblast growth factor 23 therapy experienced a reduction in their systolic BP. HTN is an important comorbidity in XLH and children should have their BP monitored regularly.