Abstract
Abstract
Introduction
X-linked Hypophosphatemia (XLH) is a genetic condition of renal phosphate wasting with multisystem complications. Children and adults with XLH have increased frequency of obesity, a risk factor for hypertension. We evaluated hypertension and left ventricular hypertrophy in children with XLH, and their relationship with XLH treatment (phosphate/active vitamin D vs burosumab).
Methods
Blood pressure and hypertension were combined and analyzed from four datasets: prospective data from the 301 burosumab vs conventional therapy randomized active-controlled trial (301 RCT, NCT 02915705) and the XLH Disease Monitoring Program (NCT 03651505), and retrospective clinical data from two tertiary centers. Hypertension was defined as three or more blood pressures ≥95th percentile for children 1-13 years of age or systolic blood pressure >130 or diastolic blood pressure >80 for children ≥13 years of age, obtained at separate clinical visits. Echocardiograms were conducted for safety monitoring in a subset of patients in the 301 RCT and these data were analyzed to assess left ventricular mass and left ventricular hypertrophy. Generalized estimating equations were used to assess the association of clinical factors and blood pressure or left ventricular hypertrophy.
Results
1,555 blood pressure readings from 252 children were evaluated. Hypertension was identified in 42/252 (17%) children and overweight/obesity was present in 51% of the cohort at baseline. 50 children underwent 310 echocardiograms, of which 22% (11/50) at baseline had left ventricular mass that met criteria for left ventricular hypertrophy. On multivariable analysis, obesity was associated with increased systolic blood pressure (Coeff 8.2, 95%CI [4.4, 12.1], p
Conclusion
Children with XLH have increased frequency of obesity, hypertension and left ventricular hypertrophy. Obesity was the main factor associated with hypertension or left ventricular hypertrophy. Longer follow-up studies are needed to assess the impact of burosumab on cardiovascular outcomes.