title: FGF-23 and cognitive performance in hemodialysis patients.
abstract: Although cognitive impairment is common in hemodialysis patients, the etiology of and risk factors for its development remain unclear. Fibroblast growth factor 23 (FGF-23) levels are elevated in hemodialysis patients and are associated with increased mortality and left ventricular hypertrophy. Despite FGF-23 being found within the brain, there are no prior studies assessing whether FGF-23 levels are associated with cognitive performance. We measured FGF-23 in 263 prevalent hemodialysis patients in whom comprehensive neurocognitive testing was also performed. The cross-sectional association between patient characteristics and FGF-23 levels was assessed. Principal factor analysis was used to derive two factors from cognitive test scores, representing memory and executive function, which carried a mean of 0 and a standard deviation of 1. Multivariable linear regression adjusting for age, sex, education status, and other relevant covariates was used to explore the relationship between FGF-23 and each factor. Mean age was 63 years, 46% were women and 22% were African American. The median FGF-23 level was 3098 RU/mL. Younger age, lower prevalence of diabetes, longer dialysis vintage, and higher calcium and phosphorus were independently associated with higher FGF-23 levels. Higher FGF-23 was independently associated with a lower memory score (per doubling of FGF-23, β = -0.08 SD [95% confidence interval, CI: -0.16, -0.01]) and highest quartile vs. lowest quartile (β = -0.42 SD [-0.82, -0.02]). There was no definite association of FGF 23 with executive function when examined as a continuous variable (β = -0.03 SD [-0.10, 0.04]); however, there was a trend in the quartile analysis (β = -0.28 SD [-0.63, 0.07], P = 0.13, for 4th quartile vs. 1st quartile). FGF-23 was associated with worse performance on a composite memory score, including after adjustment for measures of mineral metabolism. High FGF-23 levels in hemodialysis patients may contribute to cognitive impairment.
authors.affiliation: Division of Nephrology, Department of Medicine, Tufts Medical Center, Boston, MA, USA.
authors.forename: David A
authors.initials: DA
authors.lastname: Drew
authors.forename: Hocine
authors.initials: H
authors.lastname: Tighiouart
authors.forename: Tammy M
authors.initials: TM
authors.lastname: Scott
authors.forename: Kristina V
authors.initials: KV
authors.lastname: Lou
authors.forename: Li
authors.initials: L
authors.lastname: Fan
authors.forename: Kamran
authors.initials: K
authors.lastname: Shaffi
authors.forename: Daniel E
authors.initials: DE
authors.lastname: Weiner
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Sarnak
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D003071:Cognition; D003072:Cognition Disorders / Q000097:blood* / Q000209:etiology / Q000401:mortality / Q000503:physiopathology*; D003430:Cross-Sectional Studies; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000097:blood*; D006801:Humans; D017379:Hypertrophy, Left Ventricular / Q000097:blood / Q000209:etiology / Q000401:mortality / Q000503:physiopathology / Q000523:psychology; D008875:Middle Aged; D015995:Prevalence; D006435:Renal Dialysis / Q000009:adverse effects*; D012737:Sex Factors
chemical_list: C000717427:FGF23 protein, human; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23
keywords: Cognition; FGF-23; hemodialysis