A LARGE cohort study has found that greater severity of chronic kidney disease (CKD) is associated with an increased risk of developing cognitive impairment, highlighting the importance of kidney health in preserving brain function.
The study analysed data from 5,607 participants enrolled in the Chronic Renal Insufficiency Cohort (CRIC) Study, with a mean age of 59.6 years and a median follow-up of up to 16 years, depending on the cognitive test used. Researchers investigated whether two key markers of CKD severity, estimated glomerular filtration rate (eGFR) and urinary protein-to-creatinine ratio (UPCR), were associated with incident cognitive decline across several domains, including global cognition, memory, attention, processing speed, and executive function.
Cognitive performance was assessed using validated tools, including the Modified Mini-Mental State Examination, Buschke Selective Reminding Test, and Trail Making Tests. Participants with cognitive impairment at baseline were excluded, allowing the study to focus on new-onset (incident) impairment over time.
Proteinuria Strongly Associated with Cognitive Decline
The findings suggest that proteinuria may be a particularly important predictor of cognitive decline in CKD. Each standard deviation increase in log-transformed UPCR was associated with a 21% higher risk of impairment in attention and processing speed, and a 16% higher risk of impairment in executive function. While lower eGFR was initially associated with poorer attention and processing speed, this relationship was no longer significant after adjusting for UPCR, indicating that proteinuria may be the more robust marker.
Importantly, participants with both reduced kidney function (eGFR <60 mL/min/1.73 m²) and elevated proteinuria (UPCR ≥150 mg/g) had a 38% higher risk of developing global cognitive impairment compared with those with less severe CKD. This combined effect underscores the cumulative impact of multiple indicators of kidney damage on brain health.
Implications for Clinical Practice and Risk Stratification
Overall, the study demonstrates that more advanced CKD is associated with a higher incidence of cognitive impairment, particularly in domains related to attention and executive function. These findings emphasise the need for clinicians to consider cognitive outcomes when managing patients with CKD and to recognise proteinuria as a potentially important marker for identifying those at greatest risk.
Reference
Huang Z et al. Chronic Kidney Disease Severity and Risk of Cognitive Impairment. JAMA Netw Open. 2026;9(2):e2559834.
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