title: Low Vitamin D and High Fibroblast Growth Factor 23 Serum Levels Associate with Infectious and Cardiac Deaths in the HEMO Study.
abstract: Longitudinal studies testing the relationship between repeated measures of vitamin D or fibroblast growth factor 23 (FGF23) and infectious and cardiac hospitalizations and death in hemodialysis patients have not been reported. We examined the association between yearly 25-hydroxyvitamin D (25(OH)D), 1,25-dihydroxyvitamin D (1,25(OH)2D), and FGF23 serum levels and various clinical outcomes using time-dependent Cox regression models with repeated yearly measures and fixed-covariate Cox models with only baseline values after controlling for important clinical covariates in the HEMO study. During a median follow-up of 3 years, 582 of the 1340 participants died, and 499 and 514 participants had a hospitalization or death attributed to infectious and cardiac causes, respectively. Patients in the highest 25(OH)D quartile had the lowest risk of infectious events (hazard ratio [HR] 0.66 versus the lowest quartile; 95% confidence interval [95% CI], 0.49-0.89), cardiac events (HR, 0.71; 95% CI, 0.53-0.96), and all-cause mortality (HR, 0.46; 95% CI, 0.34-0.62) in time-dependent analyses. No significant associations of 1,25(OH)2D with clinical outcomes were observed in time-dependent or fixed-covariate Cox models. In contrast, the highest FGF23 quartile was associated with a higher risk of infectious events (HR, 1.57 versus the lowest quartile; 95% CI, 1.13-2.18), cardiac events (HR, 1.49; 95% CI, 1.06-2.08), and all-cause mortality (HR, 1.50; 95% CI, 1.07-2.12) in fixed-covariate Cox models. The addition of inflammation markers into the statistical models did not attenuate these associations. Thus, disordered mineral metabolism may affect outcomes in chronic hemodialysis patients.
authors.affiliation: Division of Renal Diseases and Hypertension, University of Colorado Denver, Aurora, Colorado; Michel.Chonchol@ucdenver.edu.
authors.forename: Michel
authors.initials: M
authors.lastname: Chonchol
authors.affiliation: Division of Epidemiology, University of Utah, Salt Lake City, Utah;
authors.forename: Tom
authors.initials: T
authors.lastname: Greene
authors.affiliation: Division of Epidemiology, University of Utah, Salt Lake City, Utah;
authors.forename: Yingying
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Departments of Laboratory Medicine and Medicine, University of Washington, Seattle, Washington;
authors.forename: Andrew N
authors.initials: AN
authors.lastname: Hoofnagle
authors.affiliation: Division of Nephrology & Hypertension, University of Utah, Salt Lake City, Utah; and Renal Section, Medical Service, Veterans Affairs Salt Lake City Healthcare System, Salt Lake City, Utah.
authors.forename: Alfred K
authors.initials: AK
authors.lastname: Cheung
mesh_terms: D001424:Bacterial Infections / Q000097:blood* / Q000150:complications / Q000401:mortality*; D005260:Female; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000097:blood*; D006331:Heart Diseases / Q000097:blood* / Q000150:complications / Q000401:mortality*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D006435:Renal Dialysis; D051436:Renal Insufficiency, Chronic / Q000150:complications / Q000628:therapy; D014807:Vitamin D / Q000097:blood*
chemical_list: C000717427:FGF23 protein, human; D014807:Vitamin D; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23
keywords: chronic hemodialysis; chronic inflammation; epidemiology and outcomes; fibroblast; vitamin D