title: Fibroblast Growth Factor 23 and the Risk of Infection-Related Hospitalization in Older Adults.
abstract: Within monocytes, 1,25-dihydroxyvitamin D [1,25(OH)2D] is important for production of cathelicidins, which in turn, are critical for antibacterial action. Fibroblast growth factor 23 (FGF23) decreases 1,25(OH)2D production and thus, could increase infection risk. We examined this possibility in 3141 community-dwelling adults ages ≥65 years old at baseline in the Cardiovascular Health Study using Cox proportional hazards models to examine the association between FGF23 concentrations and first infection-related hospitalizations and determine whether associations differed by the presence of CKD (eGFR<60 ml/min per 1.73 m2[n=832] or urine albumin-to-creatinine ratio >30 mg/g [n=577]). Mean±SD age of participants was 78±5 years old, 60% of participants were women, and the median plasma FGF23 concentration was 70 (interquartile range, 53-99) relative units per milliliter. In fully adjusted models, higher FGF23 concentrations associated with higher risk of first infection-related hospitalization (hazard ratio [HR], 1.11; 95% confidence interval [95% CI], 1.03 to 1.20 per doubling of FGF23) during a median follow-up of 8.6 years. In participants with or without CKD (defined by eGFR), FGF23 concentration associated with first infection-related hospitalization with HRs of 1.24 (95% CI, 1.08 to 1.42) and 1.06 (95% CI, 0.97 to 1.17) per doubling of FGF23, respectively (P=0.13 for interaction). Associations did not differ between groups when stratified by urine albumin-to-creatinine ratio. In sensitivity analyses, the addition of serum calcium, phosphorus, 25-hydroxyvitamin D, intact parathyroid hormone, and 24,25-dihydroxyvitamin D did not meaningfully change the estimates. In conclusion, in community-dwelling older adults, higher plasma FGF23 concentrations independently associated with the risk of first infection-related hospitalization.
authors.affiliation: Division of Renal Diseases and Hypertension, University of Colorado Anschutz Medical Campus, Aurora, Colorado; Kristen.Nowak@ucdenver.edu.
authors.forename: Kristen L
authors.initials: KL
authors.lastname: Nowak
authors.affiliation: Department of Biostatistics and.
authors.forename: Traci M
authors.initials: TM
authors.lastname: Bartz
authors.affiliation: Department of Medicine, University of California, Davis, Sacramento, California.
authors.forename: Lorien
authors.initials: L
authors.lastname: Dalrymple
authors.affiliation: Division of Nephrology and Kidney Research Institute, University of Washington, Seattle, Washington.
authors.forename: Ian H
authors.initials: IH
authors.lastname: de Boer
authors.affiliation: Division of Nephrology and Kidney Research Institute, University of Washington, Seattle, Washington.
authors.forename: Bryan
authors.initials: B
authors.lastname: Kestenbaum
authors.affiliation: Departments of Medicine and.|Epidemiology and Biostatistics, University of California, San Francisco, California.|General Internal Medicine Section, San Francisco Veterans Affairs Medical Center, San Francisco, California.
authors.forename: Michael G
authors.initials: MG
authors.lastname: Shlipak
authors.affiliation: Division of Nephrology, Tufts Medical Center, Boston, Massachusetts.
authors.forename: Pranav S
authors.initials: PS
authors.lastname: Garimella
authors.affiliation: Divisions of Nephrology and.|Preventative Medicine, University of California, San Diego, California; and.|Nephrology Section, Veterans Affairs San Diego Healthcare System, San Diego, California.
authors.forename: Joachim H
authors.initials: JH
authors.lastname: Ix
authors.affiliation: Division of Renal Diseases and Hypertension, University of Colorado Anschutz Medical Campus, Aurora, Colorado.
authors.forename: Michel
authors.initials: M
authors.lastname: Chonchol
mesh_terms: D000368:Aged; D001424:Bacterial Infections / Q000097:blood* / Q000453:epidemiology* / Q000628:therapy; D005260:Female; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000097:blood*; D006760:Hospitalization / Q000706:statistics & numerical data*; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D011446:Prospective Studies; D012307:Risk Factors
chemical_list: C000717427:FGF23 protein, human; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23
keywords: aging; chronic kidney disease; clinical epidemiology; infection; mineral metabolism