Yi-Chun Yeh1, Mei-Feng Huang1, Shih-Shin Liang2, Shang-Jyh Hwang3, Jer-Chia Tsai3, Tai-Ling Liu1, Ping-Hsun Wu4, Yi-Hsin Yang5, Kuang-Che Kuo6, Mei-Chuan Kuo7, Cheng-Sheng Chen8. 1. 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. 2. Department of Biotechnology, College of Life Science, Kaohsiung Medical University, Kaohsiung, Taiwan. 3. 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. 4. Division of Nephrology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan. 5. School of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan. 6. Department of Pediatrics, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan. 7. 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. 8. 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.
Abstract
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 (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.
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 (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: Benjamin Lidgard; Nisha Bansal; Leila R Zelnick; Andrew Hoofnagle; Jing Chen; Derek Colaizzo; Mirela Dobre; Katherine T Mills; Anna C Porter; Sylvia E Rosas; Mark J Sarnak; Stephen Seliger; James Sondheimer; Manjula Kurella Tamura; Kristine Yaffe; Bryan Kestenbaum Journal: J Am Soc Nephrol Date: 2022-04-20 Impact factor: 14.978