Res Sq [Preprint]. 2026 Sep 20:rs.3.rs-10922460. doi: 10.21203/rs.3.rs-10922460/v1.
ABSTRACT
INTRODUCTION: Fibroblast growth factor 23 (FGF23) regulates phosphate homeostasis and is associated with cardiovascular-kidney-metabolic syndrome in patients with chronic kidney disease in part mediated by angiotensin II. X-linked hypophosphatemia (XLH) is characterized by phosphate wasting due to excess FGF23 activity, but its associations with angiotensin peptides and cardiovascular disease remain unclear. We evaluated cross-sectional associations between angiotensin II, angiotensin-(1-7), and left ventricular mass index (LVMI) in youth with XLH.
METHODS: A pilot prospective cross-sectional study enrolled youth and young adults aged 2-24 years with XLH from nephrology and endocrinology clinics at one hospital. Individuals with acquired hypophosphatemia or inability to provide urine were excluded. LVMI was collected from echocardiograms while peptides were measured in blood and urine by radioimmunoassays. We assessed associations using Spearman correlation coefficients.
RESULTS: Among seven participants, 71% were female and median age was 12.8 years [IQR 7.7-13.7]. Seventy-one percent had a pathologic PHEX variant. Median peptide values were Ang II 56.0 pg/ml [47.2-58.1] and Ang-(1-7) 23.2 pg/ml [13.1-30.2] in blood and Ang II 32.1 pg/ml [27.5-103.2] and Ang-(1-7) 48.5 pg/ml [37.9-74.6] in urine. Median LVMI was 26.0 g/m 2.7 [21.0-28.0] and 43.9 g/BSA [39.6-47.9]. Blood and urine angiotensin peptides were not correlated with either LVMI measure ( p > 0.05).
DISCUSSION: In youth and young adults with XLH, blood and urine angiotensin peptide collection was feasible, but values were not associated with LVMI, suggesting ACE/Ang II and ACE2/Ang-(1-7) may not mediate FGF23-related cardiovascular-kidney-metabolic syndrome risk if confirmed. Larger studies are needed to determine if the renin-angiotensin-aldosterone system contributes to worse outcomes in FGF23-mediated XLH and should be targeted to improve cardiovascular-kidney-metabolic health.
PMID:42779992 | PMC:PMC13596633 | DOI:10.21203/rs.3.rs-10922460/v1