Abstract
BACKGROUND: Patients with end-stage kidney disease (ESKD) have a higher prevalence of cognitive impairment than the general population. ESKD patients also have worse white matter damage in the brain than healthy people. Some studies have shown that lower bone mineral density is associated with cognitive impairment, but few studies have investigated the relationship between bone turnover biomarkers and brain white matter damage in ESKD patients.
METHODS: Hemodialysis participants were enrolled at two hemodialysis units from August 2016 to January 2017. Participants' baseline characteristics, bone turnover proteins, and Fazekas scale of cerebral white matter lesions on magnetic resonance imaging (MRI) were recorded. Fazekas scale of periventricular (PV) lesions was defined as cerebral white matter hyperintensities on MRI ranging from grade 0 to grade 3. Multivariable ordinal regression and logistic regression models were analyzed to determine the independent association between bone turnover proteins and Fazekas scale of PV lesions.
RESULTS: In 59 hemodialysis patients, a higher grade on Fazekas scale of PV lesions was found in older patients and correlated with a lower Mini-Mental State Examination score. Among 8 bone turnover proteins, the serum level of sclerostin (SOST) showed a dose-response effect (P value for trend = 0.004), with a higher SOST level correlating with a lower grade on the Fazekas scale. After full adjustment for potential confounders, a negative association between SOST and the Fazekas scale of PV lesions remained in the ordinal regression model (odds ratio [OR]: 0.886; 95% confidence interval [CI], 0.828-0.948, P value < 0.001) and in the logistic regression model (OR: 0.821; 95% CI, 0.700-0.964, P value = 0.014).
CONCLUSION: Circulating SOST levels were negatively associated with brain white matter damage. Our study provides a potential link between bone turnover markers and brain damage.