Abstract
BACKGROUND: FGF23 mediates cardiac fibrosis through the activation of pro-fibrotic factors in in vitro models and is markedly elevated in kidney disease. Left atrial global longitudinal strain (LA GLS) derived by echocardiographic speckle-tracking measures longitudinal shortening of the LA walls, quantifies atrial performance and may enable detection of early LA remodeling in the setting of normal ventricular function. We hypothesized that LA GLS is abnormal in children on hemodialysis (HD) compared to healthy controls of comparable age/sex distribution and that, among HD patients, greater FGF23 levels are associated with abnormal LA GLS. METHODS: Clinical and echocardiographic data from 29 children receiving HD and 13 healthy controls were collected in a cross-sectional single-center study. Plasma FGF23 concentrations were measured using ELISA. The primary outcome was LA GLS measured using 2D speckle-tracking strain analysis. Linear regression analysis was used to investigate predictors of LA GLS in HD. RESULTS: Median dialysis vintage was 1.5 (IQR 0.5-4.3) years. Median intact FGF23 levels were substantially higher in the HD vs. control group (1206 [215, 4707] vs. 51 [43, 66.5] pg/ml; P = 0.0001), and LA GLS was 39.9% SD 11.6 vs. 32.8% SD 5.7 (P = 0.04). Among HD patients, higher FGF23 was associated with lower LA GLS (β per unit Ln-FGF23: - 2.7; 95% CI slope - 5.4, - 0.1; P = 0.04 after adjustment for age, body size, and HD vintage. FGF23 was not associated with LA phasic reservoir, conduit, or contractile strain. CONCLUSIONS: In children on HD and preserved left ventricular ejection fraction, greater FGF23 is associated with lower LA GLS (indicative of impaired atrial performance). A higher resolution version of the Graphical abstract is available as Supplementary information.