CKD Severity Linked to Increased Cognitive Impairment Risk

The risk of cognitive impairment increases as chronic kidney disease (CKD) progresses, with a particularly strong association between cognitive decline and both higher levels of protein in the urine and reduced kidney function, according to research published March 9, 2026, in JAMA Network Open. The findings underscore the importance of considering kidney health when assessing and managing dementia risk factors, and suggest that cognitive screening may be warranted for individuals with worsening kidney function.

Researchers at the University of Illinois College of Medicine, led by Tanika N. Kelly, PhD, MPH, analyzed data from the Chronic Renal Insufficiency Cohort Study, a long-term observational study following individuals with CKD. The study included over 5,600 participants and tracked their cognitive performance over several years using a battery of tests designed to assess various cognitive domains, including memory, attention, and executive function. Healio previously reported on related studies exploring sex-specific differences in cognitive impairment among those with CKD.

CKD Severity and Cognitive Domains

The research team found that lower estimated glomerular filtration rate (eGFR) – a measure of kidney function – was associated with impairments in attention and processing speed. Specifically, for each one standard deviation decrease in eGFR, there was a 21% increase in the risk of attention and processing speed deficits (HR = 1.21; 95% CI, 1.05-1.38). Patients with severely reduced kidney function (eGFR less than 30 mL/min/1.73 m²) faced a significantly higher risk of overall cognitive impairment compared to those with normal kidney function (eGFR greater than 60 mL/min/1.73 m²) (HR = 1.54; 95% CI, 1.05-2.27).

Elevated urinary protein-to-creatinine ratio (UPCR), an indicator of protein leakage in the urine, was also linked to cognitive decline. Each one standard deviation increase in UPCR was associated with a 21% increased risk of attention and processing speed impairments (HR = 1.21; 95% CI, 1.05-1.41) and a 16% increased risk of executive function deficits (HR = 1.16; 95% CI, 1.02-1.31). The strongest association was observed in patients with both reduced kidney function (eGFR less than 60 mL/min/1.73 m²) and high levels of protein in the urine (UPCR of at least 150 mg/g), who had a 38% higher risk of global cognitive impairment (HR = 1.38; 95% CI, 1.05-1.82).

These findings build on previous research highlighting the link between CKD and cognitive impairment. For example, a November 2025 study indicated that men and postmenopausal women with CKD are at greater risk for cognitive impairment. However, this latest study provides a more comprehensive assessment of the relationship across the entire spectrum of CKD severity.

Understanding the Connection: Beyond Kidney Function

While the study establishes a clear association between CKD severity and cognitive impairment, it does not prove causation. However, researchers suggest several potential mechanisms may underlie this connection. Dr. Kelly explained that proteinuria may signal increased susceptibility to microvascular disease processes in the brain, potentially leading to cognitive decline. “Proteinuria is intimately linked with not just kidney health, but the health of cells that line tiny blood vessels throughout the body, including the brain,” she said. Vascular damage, inflammation, and the accumulation of toxins typically cleared by the kidneys could all contribute to cognitive dysfunction.

The cognitive assessments used in the study included the Modified Mini-Mental State Examination (measuring overall cognition), the Buschke Selective Reminding test (assessing memory and recall), Trail Making Test A (measuring attention and processing speed), and Trail Making Test B (measuring executive function). These tests provide a multifaceted evaluation of cognitive abilities, allowing researchers to pinpoint specific areas of impairment associated with CKD severity.

Implications for Clinical Practice and Future Research

The study’s findings have crucial implications for clinical practice. Dr. Kelly recommends that clinicians consider cognitive screenings for patients with CKD, particularly those with worsening kidney function or noticeable cognitive or behavioral changes. “Our findings suggest that measures of CKD severity may be relevant to consider in combination with known dementia risk factors, such as age or comorbid conditions,” she stated. Early detection of cognitive impairment can allow for timely intervention and management strategies.

Further research is needed to elucidate the underlying biological pathways linking CKD and cognitive impairment. Dr. Kelly noted that while brain imaging and autopsy studies suggest vascular pathology plays a significant role, the molecular mechanisms driving these changes remain largely unknown. Recent research has also highlighted potential sex-specific differences in this relationship, warranting further investigation.

The U.S. Embassy in Manama, Bahrain issued a security alert on March 9, 2026, advising American citizens to remain vigilant and shelter in place, unrelated to the CKD study. Details are available on the embassy website. Mineralys Therapeutics also announced its fourth quarter and full year 2025 financial results on March 9, 2026. More information can be found on their investor relations page.

Looking ahead, a deeper understanding of the molecular mechanisms linking CKD and cognitive impairment could pave the way for novel therapeutic interventions aimed at preventing or slowing cognitive decline in this high-risk population. For now, proactive monitoring of kidney function and cognitive health remains crucial for individuals with CKD.