title: Fibroblast growth factor 23 levels are elevated and associated with severe acute kidney injury and death following cardiac surgery.
abstract: Fibroblast growth factor 23 (FGF23) is elevated in chronic kidney disease and associated with increased mortality, but data on FGF23 in humans with acute kidney injury (AKI) are limited. Here we tested whether FGF23 levels rise early in the course of AKI following cardiac surgery and if higher postoperative FGF23 levels are independently associated with severe AKI and adverse outcomes. Plasma C-terminal FGF23 (cFGF23) levels were measured preoperatively, at the end of cardiopulmonary bypass, and on postoperative days 1 and 3 in 250 patients undergoing cardiac surgery. We also measured intact FGF23, parathyroid hormone, phosphate, and vitamin D metabolites in a subgroup of 18 patients with severe AKI and 18 matched non-AKI controls. Beginning at the end of cardiopulmonary bypass, cFGF23 levels were significantly and consistently higher in patients who developed AKI compared with those who did not. The early increase in cFGF23 predated changes in other mineral metabolites. The levels of intact FGF23 also increased in patients who developed severe AKI, but the magnitude was lower than cFGF23. In analyses adjusted for age, preoperative eGFR, and cardiopulmonary bypass time, higher cFGF23 levels at the end of cardiopulmonary bypass were significantly associated with greater risk of severe AKI and the need for renal replacement therapy or death. Thus, cFGF23 levels rise early in AKI following cardiac surgery and are independently associated with adverse postoperative outcomes.
authors.affiliation: Division of Renal Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA. Electronic address: deleaf@partners.org.
authors.forename: David E
authors.initials: DE
authors.lastname: Leaf
authors.affiliation: Endocrine Unit and Pediatric Nephrology Unit, Massachusetts General Hospital, Boston, Massachusetts, USA; Department of Medicine, New York Medical College, Valhalla, NY.
authors.forename: Marta
authors.initials: M
authors.lastname: Christov
authors.affiliation: Endocrine Unit and Pediatric Nephrology Unit, Massachusetts General Hospital, Boston, Massachusetts, USA.
authors.forename: Harald
authors.initials: H
authors.lastname: Jüppner
authors.affiliation: Division of Nephrology and Hypertension, Vanderbilt Center for Kidney Disease, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
authors.forename: Edward
authors.initials: E
authors.lastname: Siew
authors.affiliation: Division of Nephrology and Hypertension, Vanderbilt Center for Kidney Disease, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
authors.forename: T Alp
authors.initials: TA
authors.lastname: Ikizler
authors.affiliation: Department of Biostatistics, Vanderbilt Center for Kidney Disease, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
authors.forename: Aihua
authors.initials: A
authors.lastname: Bian
authors.affiliation: Department of Biostatistics, Vanderbilt Center for Kidney Disease, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
authors.forename: Guanhua
authors.initials: G
authors.lastname: Chen
authors.affiliation: Division of Renal Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA.
authors.forename: Venkata S
authors.initials: VS
authors.lastname: Sabbisetti
authors.affiliation: Division of Renal Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA.
authors.forename: Joseph V
authors.initials: JV
authors.lastname: Bonventre
authors.affiliation: Division of Nephrology, Department of Medicine and Center for Translational Metabolism and Health, Institute for Public Health and Medicine, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA.
authors.forename: Xuan
authors.initials: X
authors.lastname: Cai
authors.affiliation: Division of Nephrology, Department of Medicine and Center for Translational Metabolism and Health, Institute for Public Health and Medicine, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA.
authors.forename: Myles
authors.initials: M
authors.lastname: Wolf
authors.affiliation: Division of Renal Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA.
authors.forename: Sushrut S
authors.initials: SS
authors.lastname: Waikar
mesh_terms: D058186:Acute Kidney Injury / Q000097:blood* / Q000209:etiology; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D006348:Cardiac Surgical Procedures / Q000009:adverse effects*; D016022:Case-Control Studies; D005260:Female; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000097:blood*; D006801:Humans; D008297:Male; D010281:Parathyroid Hormone / Q000097:blood; D010710:Phosphates / Q000097:blood; D011183:Postoperative Complications / Q000097:blood*; D011446:Prospective Studies; D014807:Vitamin D / Q000097:blood
chemical_list: D015415:Biomarkers; C000717427:FGF23 protein, human; D010281:Parathyroid Hormone; D010710:Phosphates; D014807:Vitamin D; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23
keywords: AKI; RRT; cardiopulmonary bypass; fibroblast growth factor 23