Poor Kidney Function Impedes Blood Flow to the Brain

Pam Harrison

August 12, 2015

Poor kidney function negatively affects cerebral blood flow and may be linked to both stroke and dementia independent of known cardiovascular disease risk factors, a population-based Rotterdam study suggests.

The study, by Sanaz Sedaghat, MSc, from the Department of Epidemiology, Erasmus University Medical Center, Rotterdam, the Netherlands, and colleagues, was published online August 6 in the Journal of the American Society of Nephrology.

"Our findings show that damage to the kidney indicates there is damage to the brain," senior investigator Arfan Ikram, MD, PhD, also from Erasmus University Medical Center, told Medscape Medical News.

"So kidney disease should not be considered in isolation but, rather, physicians should realize that kidney disease may also affect the brain and vice versa: To understand brain diseases such as stroke and dementia, physicians should realize that the kidney can play a contributing role."

The Rotterdam study included 2645 participants with a mean age of 56.6 years.

Investigators used the estimated glomerular filtration rate (eGFR), as well as the albumin-to-creatinine ratio, to assess kidney function, and phase-contrast magnetic resonance imaging of basilar and carotid arteries to measure cerebral blood flow.

On average, participants had an eGFR of 86.3 mL/minute per 1.73 m2 and a median albumin-to-creatinine ratio of 3.2 mg/g.

After adjusting for potential confounders, a higher albumin-to-creatinine ratio was not associated with lower levels of cerebral blood flow.

In contrast, after adjusting for known cardiovascular disease risk factors, each one standard deviation higher eGFR was associated with increased cerebral blood flow. Specifically, when eGFR was calculated using the combination of creatinine and cystatin C, each standard deviation increase in eGFR was associated with a 0.42 mL/minute per 100 mL higher cerebral blood flow (95% confidence interval [CI], 0.01 - 0.83). Similarly, when eGFR was calculated on the basis of creatinine alone, each one standard deviation was associated with a 0.48 mL/minute per 100 mL higher level of cerebral blood flow (95% CI, 0.11 - 0.85).

"We observed a linear trend between different categories of kidney function and cerebral blood flow, indicating lower cerebral blood flow in persons with worse kidney function," the investigators add.

Furthermore, among individuals with lower levels of cerebral blood flow, each one standard deviation lower eGFR (calculated on the basis of creatinine and cystatin C) was associated with a 62% higher prevalence of stroke or dementia (odds ratio, 1.62; 95% CI, 1.01 - 2.36).

In contrast, no association between the same measure of kidney function and stroke or dementia was seen among individuals with high levels of cerebral blood flow.

There was also no association between stroke or dementia and the albumin-to-creatinine ratio in individuals with either high or low levels of cerebral blood flow.

Investigators also observed that individuals with both low levels of eGFR (again calculated on the basis of creatinine and cystatin C) and low cerebral blood flow performed more poorly on cognitive testing than their counterparts with high levels of kidney function and cerebral blood flow.

As Dr Ikram noted, conditions such as hypertension, smoking, and diabetes all can cause poor kidney function, and all are known to affect the brain as well.

"Many elderly people have subclinical kidney dysfunction, but they are not aware of it," he noted. "But they should be brought to the attention of clinical care, as it's not only important that their kidney function be properly managed, but given the effects the kidney has on the brain, there are additional reasons for these patients to be better monitored," Dr Ikram said.

Investigators also emphasized that their findings were not confined to patients with chronic kidney disease, but to the general population without overt kidney disease at study onset.

One coauthor works in ErasmusAGE, a center for aging research across the life course funded by Nestlé Nutrition (Nestec Ltd), Metagenics Inc, and AXA. The other authors have disclosed no relevant financial relationships.

J Am Soc Nephrol. Published online August 6, 2015. Abstract

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