Relationship between serum fibroblast growth factor 23 levels and left ventricular mass measured by three-dimensional echocardiography in patients with end-stage renal disease

Abstract

Purpose: In patients with chronic renal insufficiency traditional risk factors of left ventricular (LV) hypertrophy include hypertension, overhydration, anemia and impaired calcium-phosphate homeostasis. Fibroblast growth factor 23 (FGF-23) is a phosphaturic hormone secreted by osteoblasts and a rising biomarker associated with LV hypertrophy and mortality in patients with end-stage renal disease (ESRD). We sought to determine the relationship between serum FGF-23 levels and left venticular mass measured by three-dimensional (3D) echocardiography in ESRD patients. Methods: This retrospective cohort study included 44 patients (mean age 48±13 years, 54% men) with ESRD on three times per week maintenance hemodialysis. Exclusion criteria were previous history of diabetes and any significant cardiac disease. Beyond conventional transthoracic echocardiographic examination, 3D recordings were obtained using multi-beat reconstruction from 6 consecutive cardiac cycles (GE Vivid E9). After semi-automated tracing of LV endo- and epicardial surface at end-diastolic frame, LV mass was calculated using dedicated software (GE 4D Auto LVQ). Serum FGF-23 levels were measured by enzyme-linked immunosorbent assay (Merck Millipore). Overhydration evaluated by bioimpedance (Fresenius Body Composition Monitor), laboratory test results (including serum calcium, phosphate, parathormone, total iron binding capacity levels) and blood pressure were recorded and averaged in the three previous months. Relationships were calculated by Spearman correlation test and multivariate linear regression. Results: The median value of LV mass measured in ESRD patients was 244 grams (interquartile range 97.5). Serum FGF-23 levels ranged between 34 and 6848 with a median of 687 pg/ml. Serum levels of FGF-23 (ρ=0.52), phosphate (ρ=0.55), parathormone (ρ=0.38), total iron binding capacity (ρ=0.61), systolic blood pressure (ρ=0.38) and pulse pressure (ρ=0.47, all p<0.05) correlated significantly with LV mass. FGF-23 correlated with serum phosphate (ρ=0.83) and parathormone (ρ=0.53, both p<0.001) levels. In a multivariate linear regression model, FGF-23 (β=0.42, p<0.001), total iron binding capacity (β=0.49, p<0.001) and systolic blood pressure (β=0.37, p<0.01) were found to be independent predictors of LV mass. Conclusions: To the best of our knowledge, this is the first study which demonstrates the strong correlation between serum FGF-23 levels and LV mass measured by 3D echocardiography. Beside the chronic volume- and pressure overload, LV hypertrophy is strongly determined by the endocrine effects of FGF-23 in patients with ESRD.