Indoxyl sulfate, not p-cresyl sulfate, is associated with cognitive impairment in early-stage chronic kidney disease

Backgrounds: 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 (beta = 031, 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. (C) 2016 Elsevier Inc. All rights reserved.