Relationships between serum Klotho concentrations and cognitive performance among older chronic kidney disease patients with albuminuria in NHANES 2011-2014

Abstract

Background: The potential relationship between Klotho and cognitive function is limited and controversial. This study aimed to quantify the association of Klotho and cognitive impairment in chronic kidney disease (CKD) patients with albuminuria. Methods: Serum Klotho was measured by enzyme-linked immunosorbent assay. Patients with urine albumin to creatinine ratio (UACR) > 30mg/g from the National Health and Nutrition Survey (NHANES) 2011-2014 were divided into 4 groups according to the quartile of Klotho. Cognitive function was examined using the Consortium to Establish a Registry for Alzheimer’s Disease (CERAD), Digit Symbol Substitution Test (DSST), and Animal Fluency Test. The relationship between Klotho and cognitive function was analyzed by multivariable regression and subgroup analysis. Results: Among 368 CKD patients with albuminuria, we found that Klotho was negatively associated with creatinine, and positively associated with hemoglobin, and estimated glomerular filtration rate. No significant linear relationship was showed between Klotho (as a continuous variable) and cognitive function. When regarded Klotho as a category variable, patients in the quartile 3 group were at a better cognitive performance for CEARD-word learning subset and DSST, especially in the CKD patients with 30 mg/g < UACR <300 mg/g, but not in participants with UACR > 300 mg/g. Conclusions: The increased Klotho was associated with an increased cognitive function in CKD patients with microalbuminuria. Further studies are needed to demonstrate whether Klotho may be a beneficial biomarker of cognitive health and neurodegeneration.