FGF-23 and cognitive performance in hemodialysis patients

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, beta = -0.08 SD [95% confidence interval, CI: -0.16, -0.01]) and highest quartile vs. lowest quartile (beta = -0.42 SD [-0.82, -0.02]). There was no definite association of FGF 23 with executive function when examined as a continuous variable (beta = -0.03 SD [-0.10, 0.04]); however, there was a trend in the quartile analysis (beta = -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.