Associations between small and middle molecules clearance and the change of cognitive function in peritoneal dialysis

Abstract

Background Uremic toxins have been suspected as potential contributors for cognitive impairment in peritoneal dialysis (PD) patients. However, associations between the clearance of serum small and middle molecules and the change of cognitive function were not fully explored and then we explored this issue in the present study. Method A total of clinically-stable 222 patients on PD were enrolled and then followed up for 2 years in this single-center prospective cohort study. Small and middle molecules clearances were examined by urea clearance (Kt/V), creatinine clearance (Ccr) and beta-2 microglobulin (B2M) clearance via dialysate and urine at baseline and after 2 years. Global and specific cognitive impairment were measured at baseline and after 2 years. Modified Mini-Mental State Examination (3MS) was assessed for global cognitive function, trail-making tests A and B for executive function and subtests of the battery for the assessment of neuropsychological status for immediate and delayed memory, visuospatial skills and language ability. Results The median of total Kt/V, Ccr and B2M clearance were 1.89, 53.2 l/w/1.73 m 2 and 17.5 l/w/1.73 m 2 , respectively at baseline. The prevalence of global cognitive impairment was 12.3% for 222 patients and 15.4% for the remained 130 patients after 2 years. At baseline, total Kt/V was independently positively associated with delayed memory function. Total and dialysate beta-2 microglobulin clearance was positively associated with 3MS scores and negatively with completion time on trail A after multivariate adjustment. At 2 years, we observed a significant difference in the changing trend of 3MS scores between groups divided by total B2M clearance (P = 0.033), which still maintained to be meaningful after multivariate adjustment (P = 0.024). Patients with total B2M clearance > 19.0 l/w/1.73 m 2 got significant improvement on their 3MS scores (P = 0.005). Patients divided by total Kt/V or Ccr were not significantly different in the trends of general and any specific cognitive function during the follow up. Conclusion The higher middle molecules clearance independently correlated to better performance on general cognitive and executive function in PD patients, which also predict an improvement in general cognitive function during the follow up.

Incident dementia in kidney transplantation recipients: a matched comparative nationwide cohort study in South Korea

“…Consistent with previous studies, our results revealed that dialysis-dependent ESRD patients have an increased risk of incident all-cause dementia/Alzheimer disease/vascular dementia compared to the GP. Pathophysiologic mechanisms for the occurrence and progression of dementia in patients with CKD and dialysis-dependent ESRD have been reported to be traditional risk factors like older age, hypertension, diabetes mellitus, dyslipidemia, and cardiovascular disease; nontraditional kidney disease-related factors such as albuminuria, retention of uremic toxin, anemia, and vascular calcification; and ESRD treatment-associated risk factors including intradialytic hypotension, cerebral edema, and thrombotic events [4,6,20,[24][25][26][27][28][29][30][31][32].…”

“…Pathophysiologically, KT may reverse the underlying mechanisms that cause cognitive impairment in ESRD patients, including nontraditional kidney disease-related factors and ESRD treatment-associated factors, as mentioned above [ 15 ]. A previous study reported that high middle molecule clearance rates improve general cognitive and executive functions in patients undergoing peritoneal dialysis [ 31 ]. Since insufficient middle molecule clearance (a limitation of current dialysis) is improved in post-KT patients, it may have an impact on the low incidence of dementia found.…”

Uremic Toxins and Frailty in Patients with Chronic Kidney Disease: A Molecular Insight

“…A majority of inflammatory mediators, including interleukins, induces cerebral inflammation and oxidative damages, causing excitotoxic injuries and the resultant neurodegeneration [76]. An enhanced clearance of middle molecules also correlates closely with a better cognitive performance and executive function in ESRD patients [77].…”