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“Our study highlights the importance of the kidney-brain connection,” says Dr. Mark Fisher, professor of neurology in the UCI School of Medicine and corresponding author. “It was previously thought that CKD effects on the brain were due to hypertension. We discovered the first clear evidence that CKD can produce cerebrovascular disease independent of high blood pressure.” UCI School of Medicine

Irvine, Calif., May 3, 2023 — A study led by University of California, Irvine neurology and nephrology experts has revealed the first clear link between chronic kidney disease and increased cerebrovascular disease. It was previously thought that renal disease’s effects on the brain were largely due to hypertension, but researchers discovered that CKD promoted the development of cerebral microhemorrhages independent of blood pressure.

Findings, recently published online in the Journal of Neuroinflammation, show that a mix of gut-derived bacteria-dependent toxins and urea, which accumulates in kidney failure, can cause vascular injury and microhemorrhages in the brain.

“CKD is increasingly recognized as a stroke risk factor, but its exact relationship with cerebrovascular disease is not well understood. Our study provides crucial insights into the underlying mechanisms of brain injury that can occur in CKD, offering new therapeutic targets that involve treating kidney disease,” said Dr. Mark Fisher, professor of neurology in the UCI School of Medicine and corresponding author. “Observations have shown that people with advanced kidney disease are at a higher risk for stroke, suggesting that we can ultimately enhance brain health by reducing renal disease.”

Researchers randomly divided aged female and male mice into control and CKD groups. They found that CKD produces brain microhemorrhages without hypertension and to a greater extent in mice with more severe kidney injury. They also observed a sex difference, whereby males showed a more pronounced increase in microhemorrhages than females.

“The effects of CKD are associated with blood-brain barrier impairment, which is caused by uremic toxins and microglia, the brain’s resident immune cells. We know that inflammatory cells in the brain play an important role in how CKD causes cerebrovascular disease, but we need to understand this relationship in better detail,” said Dr. Wei Ling Lau, associate professor of medicine-nephrology in the UCI School of Medicine. “It remains to be seen if just treating kidney disease by itself will improve brain health.”

The team also included researchers from the departments of neurology, medicine-nephrology, pathology & laboratory medicine in the UCI School of Medicine, the UCI Institute for Memory Impairments and Neurological Disorders, and the department of biomedical and pharmaceutical sciences in the School of Pharmacy at Chapman University.

This work was supported by National Institute of Neurological Disorders and Strokes under award numbers R01NS20989 and R01NS113337, and by the National Institutes of Aging, R01AG072896 and R01AG062840, of the National Institutes of Health.

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