New research from the University of Colorado Anschutz Department of Medicine is shedding light on how women and men with chronic kidney disease (CKD) may fare differently as they age and their disease progresses.
Among patients with end-stage kidney disease who receive hemodialysis, a treatment that filters waste and excess fluid from the blood when the kidneys can no longer function adequately, frailty and physical weakness are associated with a higher risk of cognitive impairment.
But what about patients in earlier stages of CKD who don’t need dialysis yet? A July 2026 paper from experts in the Division of Renal Diseases and Hypertension studied a cohort of nearly 1,400 patients with mild to moderate CKD who were not on dialysis. The researchers found that, although women in the cohort were more likely to be frail, men had a higher rate of cognitive impairment. Among men, those who were frail had more than twice the risk of developing cognitive impairment compared with men who were not frail.
Surprisingly, frailty appeared to be a bigger risk factor for men than it was for women. Frail men were more likely than non-frail men to show cognitive impairment over the subsequent few years, but women didn’t show a similar trend.
Study co-authors Stephanie Lapierre-Nguyen, PhD, and Ester Oh, PhD, MS, say that their work aims to pinpoint patients at higher risk for cognitive impairment so health professionals can intervene before their condition worsens. Lapierre-Nguyen is the postdoctoral fellow who led the study, while Oh is an assistant professor of renal medicine and senior author of the paper.
“We can’t always identify early CKD and prevent the disease from manifesting, but we can identify frailty in these patients, so maybe intervening early on in the non-frail and the pre-frail CKD patients can help preserve their cognitive function,” says Lapierre-Nguyen. “It might be too late to prevent CKD from starting, but we can still try and prevent a lot of the negative consequences of CKD, like cognitive impairment.”
Kidney function and cognitive impairment
The kidneys’ main job in the body is to filter the blood and remove excess fluids and waste. When kidney disease sets in, the kidneys stop filtering as well, so toxins can start accumulating in the blood.
Patients with CKD often experience cognitive impairment, in part because of inflammation in blood vessels and tissues and because there are neurodegenerative processes directly tied to kidney disease.
Because cognitive impairment can have such a negative impact on patients’ quality of life, the researchers in this study sought to better understand the early risk factors for cognitive impairment in mild to moderate CKD patients. They examined the concept of frailty, which they defined as deteriorating bodily functioning along with a growing vulnerability to illnesses and environmental stressors.
A person is pictured taking a hand grip test. Reduced grip strength can be an indicator of frailty. (Photo courtesy of Stephanie Lapierre-Nguyen and Ester Oh)
Frail older adults generally face a higher risk of dementia and other cognitive impairment. By the time they reach end-stage kidney disease and require dialysis, about 70% of patients show signs of frailty, and cognitive impairment is also relatively common.
But the researchers were interested in studying how frailty would affect the outlook for patients with CKD who were not on dialysis yet. They anticipated that frail earlier-stage CKD patients would be more likely to show declining performance on a cognitive function assessment called the 3MS (the Modified Mini-Mental State Examination).
Across the entire group of patients with mild to moderate CKD, the researchers did not find a significant link between frailty and cognitive impairment. However, when the researchers examined men and women separately, they found an association among men but not women.
Frail men had greater subsequent declines in 3MS scores than non-frail men, whereas frailly was not associated with cognitive impairment among women. Although women were more likely to be frail (16%) compared to men (9%), men were more likely to develop cognitive impairment during follow up.
Sex differences in cognitive risks for CKD patients
What might be different for women with CKD compared to men? Lapierre-Nguyen says there could be lifestyle, social, or behavioral factors that help frail women with CKD ward off cognitive impairment.
“These frail men may not have a good social network or family support, or their nutrition might not be great. These things can really influence their cognitive impairment compared to the women,” she says.
Lapierre-Nguyen believes health care providers could provide nutrition guidelines, exercise regimens, and other lifestyle interventions to proactively prevent frailty in patients with CKD before it contributes to cognitive impairment as the disease progresses.
And senior study author Oh, who has conducted extensive research on sex differences in cardiovascular and cognitive impairment risk in patients with CKD, also emphasizes that although men with CKD have a higher risk of cognitive impairment than women, women with CKD remain at substantial risk and should not be overlooked.
“People are often more interested in men with CKD because they have a higher risk for cardiovascular disease and cognitive impairment than women. However, it is also very important to focus on women with CKD, who remain at a much higher risk of cognitive impairment than the general population,” she says.
