title: Indoxyl sulfate, not p-cresyl sulfate, is associated with cognitive impairment in early-stage chronic kidney disease.
abstract: BACKGROUND
  Patients with chronic kidney disease (CKD) more commonly experience cognitive impairment, but the etiologies are not clear. Uremic toxins such as p-cresyl sulfate (PCS) and indoxyl sulfate (IS) have been shown to increase the risks of cardiovascular diseases and mortality; however, no study has investigated the associations of PCS and IS with cognitive function in patients with CKD.
  
  
  METHODS
  Patients with CKD aged ≥50 years and age- and sex-matched non-CKD comparison subjects were recruited. CKD stage was defined according to the National Kidney Foundation guidelines. Cognitive function was evaluated using comprehensive neuropsychological tests. The associations between uremic toxins and cognitive function domains were examined using multiple linear regression analysis. The interaction between uremic toxins and CKD stages on cognitive functions were also examined.
  
  
  RESULTS
  In total, 199 patients with CKD and 84 comparison subjects completed the study. The patients with CKD had poorer cognitive function and higher serum PCS and IS levels. A higher serum IS level was associated with poor executive function (β=-0.31, P=0.003) only in stage 3 CKD patients after adjustment for age, sex and educational level. Serum PCS level was not associated with cognitive function in patients with CKD.
  
  
  CONCLUSIONS
  Our study showed that a higher serum IS level was associated with poor executive function in the early stage of CKD. It would be worthwhile to investigate the effect of IS removal in early-stage CKD on the prevention of cognitive impairment in future studies.
authors.affiliation: Department of Psychiatry, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Department of Psychiatry, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Yi-Chun
authors.initials: YC
authors.lastname: Yeh
authors.affiliation: Department of Psychiatry, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Department of Psychiatry, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Mei-Feng
authors.initials: MF
authors.lastname: Huang
authors.affiliation: Department of Biotechnology, College of Life Science, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Shih-Shin
authors.initials: SS
authors.lastname: Liang
authors.affiliation: Faculty of Renal Care, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Division of Nephrology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Shang-Jyh
authors.initials: SJ
authors.lastname: Hwang
authors.affiliation: Faculty of Renal Care, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Division of Nephrology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Jer-Chia
authors.initials: JC
authors.lastname: Tsai
authors.affiliation: Department of Psychiatry, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Department of Psychiatry, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Tai-Ling
authors.initials: TL
authors.lastname: Liu
authors.affiliation: Division of Nephrology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Ping-Hsun
authors.initials: PH
authors.lastname: Wu
authors.affiliation: School of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Yi-Hsin
authors.initials: YH
authors.lastname: Yang
authors.affiliation: Department of Pediatrics, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.
authors.forename: Kuang-Che
authors.initials: KC
authors.lastname: Kuo
authors.affiliation: Faculty of Renal Care, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Division of Nephrology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan. Electronic address: mechku@kmu.edu.tw.
authors.forename: Mei-Chuan
authors.initials: MC
authors.lastname: Kuo
authors.affiliation: Department of Psychiatry, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Department of Psychiatry, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan. Electronic address: sheng@kmu.edu.tw.
authors.forename: Cheng-Sheng
authors.initials: CS
authors.lastname: Chen
mesh_terms: D000368:Aged; D016022:Case-Control Studies; D003072:Cognition Disorders / Q000139:chemically induced*; D003408:Cresols / Q000627:therapeutic use*; D056344:Executive Function / Q000187:drug effects*; D005260:Female; D006801:Humans; D007200:Indican / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D051436:Renal Insufficiency, Chronic / Q000188:drug therapy; D013463:Sulfuric Acid Esters / Q000627:therapeutic use*
chemical_list: D003408:Cresols; D013463:Sulfuric Acid Esters; C408690:4-cresol sulfate; D007200:Indican
keywords: Chronic kidney disease; Cognitive function; Indoxyl sulfate; Uremic toxin; p-Cresyl sulfate