Fibroblast Growth Factor 23 Levels Associate with AKI and... : Journal of the American Society of Nephrology (original) (raw)

Clinical Research

Fibroblast Growth Factor 23 Levels Associate with AKI and Death in Critical Illness

Leaf, David E.*; Jacob, Kirolos A.†; Srivastava, Anand*; Chen, Margaret E.*; Christov, Marta‡,§; Jüppner, Harald‡; Sabbisetti, Venkata S.*; Martin, Aline‖; Wolf, Myles¶; Waikar, Sushrut S.*

*Division of Renal Medicine, Brigham and Women’s Hospital, Boston, Massachusetts;

†Department of Cardiothoracic Surgery, University Medical Center, Utrecht, Utrecht, The Netherlands;

‡Endocrine Unit and Pediatric Nephrology Unit, Massachusetts General Hospital, Boston, Massachusetts;

§Department of Medicine, New York Medical College, Valhalla, New York;

‖Division of Nephrology and Hypertension, Department of Medicine and Center for Translational Metabolism and Health, Institute for Public Health and Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois; and

¶Division of Nephrology, Department of Medicine, Duke University School of Medicine, Durham, North Carolina

Correspondence: Dr. David E. Leaf, Renal Division, Brigham and Women’s Hospital, 75 Francis Street, Boston, MA 02115. Email: [email protected]

Abstract

Elevated plasma levels of the osteocyte-derived hormone fibroblast growth factor 23 (FGF23) have emerged as a powerful biomarker of cardiovascular disease and death in patients with CKD. Whether elevated urinary or plasma FGF23 levels are prospectively associated with AKI and death in critically ill patients is unknown. We therefore conducted a prospective cohort study of 350 critically ill patients admitted to intensive care units at an academic medical center to investigate whether higher urinary FGF23 levels associate with the composite end point of AKI or in-hospital mortality (AKI/death). We measured urinary FGF23 levels within 24 hours of admission to the intensive care unit. In a subcohort (_n_=131) we also measured plasma levels of FGF23, calcium, phosphate, parathyroid hormone, and vitamin D metabolites. Urinary and plasma FGF23 levels, but not other mineral metabolites, significantly associated with AKI/death. In multivariate analyses, patients in the highest compared with the lowest quartile of urinary FGF23 had a 3.9 greater odds (95% confidence interval, 1.6 to 9.5) of AKI/death. Higher urinary FGF23 levels also independently associated with greater hospital, 90-day, and 1-year mortality; longer length of stay; and several other important adverse outcomes. In conclusion, elevated FGF23 levels measured in the urine or plasma may be a promising novel biomarker of AKI, death, and other adverse outcomes in critically ill patients.