Plasma Total Fibroblast Growth Factor 23 Levels Are Associated With Acute Kidney Injury And Mortality In Children With Acute Respiratory Distress Syndrome

Acute respiratory distress syndrome (ARDS) has high rates of mortality and multisystem morbidity. Pre-clinical data suggest that fibroblast growth factor 23 (FGF23) may contribute to pulmonary pathology, and FGF23 is associated with mortality and morbidity, including acute kidney injury (AKI), in non-ARDS cohorts. Here, we assess whether FGF23 is associated with AKI and/or mortality in a cohort of 161 pediatric ARDS patients. Plasma total (intact + C-terminal) FGF23 and intact FGF23 concentrations were measured within 24 hours of ARDS diagnosis (Day 1), and associations with Day 3 AKI and 60-day mortality were evaluated. 35 patients (22%) developed AKI by 3 days post-ARDS diagnosis, and 25 (16%) died by 60 days post-ARDS diagnosis. In unadjusted models, higher Day 1 total FGF23 was associated with Day 3 AKI (odds ratio (OR) 2.22 [95% confidence interval (CI) 1.62, 3.03], p< 0.001), but Day 1 intact FGF23 was not. In a model adjusted for demographics and disease severity, total FGF23 remained associated with AKI (OR 1.52 [95% CI 1.02, 2.26], p = 0.039). In unadjusted models, both higher Day 1 total and intact FGF23 were associated with 60-day mortality (OR 1.43 [95% CI 1.07, 1.91], p = 0.014; and OR 1.44 [95% CI 1.02, 2.05], p = 0.039, respectively). In the adjusted model, only total FGF23 remained associated with 60-day mortality (OR 1.62 [95% CI 1.07, 2.45], p = 0.023). In a subgroup analysis of patients with Day 1 plasma IL-6 concentrations available, inflammation partially mediated the association between total FGF23 and AKI. Our data suggest both inflammation-dependent and inflammation-independent associations between total FGF23 and clinical outcomes in pediatric ARDS patients.