Elevated circulating fibroblast growth factor 23 is associated with acute kidney injury and mortality in coronavirus disease 2019 (COVID-19)

Abstract Introduction: Acute kidney injury (AKI) is a key negative prognostic factor for survival in patients hospitalized with COVID-19, but few reliable biomarkers for AKI and mortality exist. This study aimed to evaluate whether elevated fibroblast growth factor 23 (FGF23) levels are associated with AKI status and mortality in COVID-19 patients. Methods: In this prospective cohort of 111 COVID-19 patients hospitalized at the Indiana University Academic Health Center (April–October 2020), circulating FGF23 and its co-receptor Klotho levels were assessed for association with AKI and 28-month survival. Results: Of the 111 patients, 77 had no AKI (91.0 [69.2, 101.3] mL/min/1.73 m2), 17 had AKI (39.7 [28.7, 57.8] mL/min/1.73 m2), and 17 had end-stage kidney disease (ESKD; 11.9 [8.6, 17.5] mL/min/1.73 m2). Median follow-up was 22.6 months. Median FGF23 levels were higher in patients with AKI (305.6 [134.6, 350.8] RU/mL) and ESKD (3,607.6 [440.5, 7,452.7] RU/mL) compared to those without AKI (120.7 [64.3, 249.7] RU/mL; P < 0.001). Patients (excluding those with ESKD) with elevated FGF23 levels had increased odds of having AKI (OR: 2.30, 95% CI: [1.31, 4.03]; P = 0.004). Moreover, each unit increase in log(FGF23) was associated with a 45% higher risk of mortality in the cohort (HR: 1.45, 95% CI: [1.02, 2.07]; P = 0.04) after controlling for age, cardiovascular disease, and BMI. Klotho levels differed by group (without AKI: 576.1 [455, 730] pg/mL; with AKI: 594.6 [416, 774] pg/mL; ESKD: 421.5 [330, 562] pg/mL; P = 0.04), but were not associated with AKI status. Conclusion: Elevated FGF23 is associated with AKI status and mortality in patients with COVID-19.