HUNTINGTON, W.Va. – A new study published in the American Journal of Physiology - Heart and Circulatory Physiology reveals that chronic kidney disease (CKD) accelerates cognitive decline through interconnected damage to the heart and brain—and that these pathways differ markedly between men and women.
Scientists and physicians from the Marshall University Joan C. Edwards School of Medicine, in collaboration with the National Institute on Aging at the National Institutes of Health (NIH), led the study to better understand sex-specific crosstalk within the kidney–heart–brain axis in CKD. The cross-sectional study included community-dwelling patients with equal representation of both sexes and a focus on a rural population.
The research found that men with CKD experienced greater cognitive impairment and more pronounced reductions in cardiac function than women, suggesting a stronger heart–brain contribution to cognitive deterioration in men. These findings shed light on why men with CKD often face more severe cognitive effects and point to potential sex-specific targets for early diagnosis and treatment.
"These results demonstrate that the biological pathways linking the kidney, heart, and brain are distinct in men and women," said Sneha S. Pillai, Ph.D., research assistant professor of biomedical sciences at the Joan C. Edwards School of Medicine and lead author of the study.
CKD affects millions of Americans, yet its relationship with cognitive impairment remains underrecognized—particularly in rural and underserved populations. By uncovering sex-dependent mechanisms of kidney–heart–brain interaction, the study opens new pathways for early screening and personalized interventions.
"Understanding how cardiovascular stress and neurodegenerative markers interact differently in men and women with CKD could fundamentally change how we approach treatment," said Komal Sodhi, M.D., associate professor of surgery at the Joan C. Edwards School of Medicine and principal investigator of the study. "This work underscores the urgency of tailored strategies to prevent progression to more serious neurological disorders."
Ellen Thompson, M.D., professor of cardiology, and Zeid J. Khitan, M.D., professor of nephrology, contributed to the clinical aspects of the research. Research support was provided, in part, by the NIH Office of Research on Women's Health through the Bench-to-Bedside and Back Program (Award #736214), and by NIH grant R01 HL164460-01A1.
To view the article titled "Chronic Kidney Disease and Cardiac Remodeling Potentiate Cognitive Impairment Progression: Disentangling the Sex-Specific Crosstalk of Kidney-Heart-Brain Axis," please visit https://doi.org/10.1152/ajpheart.00617.2025 .
