Association of Urinary Biomarkers of Renal Tubular Injury with Cognitive Dysfunction in Older Patients with Chronic Kidney Disease: A Cross-Sectional Observational Study

Epidemiological data suggest that individuals in all stages of chronic kidney disease (CKD) have higher risks of developing cognitive impairment. The relationship between CKD and cognition has been assessed exclusively using glomerular function markers; however, kidney tubule injury has not been assessed. We assessed the association between urinary biomarkers of renal tubular injury and cognitive dysfunction in older patients with CKD Stages 3-4. According to the Montreal Cognitive Assessment, participants were divided into cognitive dysfunction and control groups. Compared with the control group, the cognitive dysfunction group had significantly higher percentages of smokers, noticeably lower average education, and higher mitochondrial DNA (mtDNA) levels in the peripheral blood. Spearman correlation analysis showed that higher urine neutrophil gelatinase-associated lipocalin, kidney injury molecule-1, and beta-2 microglobulin (beta 2M) levels were significantly associated with lower cognitive scores. Multivariate logistic regression analysis showed that only increased urinary beta 2M levels were independently associated with cognitive worsening in CKD after adjusting for confounders. Logistic regression identified a promising role of urinary beta 2M combined with smoking and education for predicting cognitive impairment in CKD. Urinary beta 2M and cognitive function negatively correlated with mtDNA content, suggesting that mitochondrial dysfunction is a common pathophysiological mechanism linking CKD and cognitive dysfunction.