Poorer Kidney Function Associated With Cerebral Small Vessel Disease

Caroline Cassels
January 21, 2008 — New research suggests that poor kidney function, which is known to increase cardiovascular risk, might also be associated with subclinical markers of cerebral small vessel disease, independent of cardiovascular risk factors.
In a large population-based study, investigators from Erasmus Medical Center, the Netherlands, found that individuals with a lower glomerular filtration rate (GFR) had less deep white-matter volume (WMV), more white-matter lesions (WML), and a more frequent presence of lacunar infarcts, although this did not reach statistical significance.
Furthermore, adjustment for cardiovascular risk factors, such as blood pressure, C-reactive protein (CRP), and homocysteine, only marginally changed the association between GFR and cerebral small vessel disease, a common cause of stroke, cognitive decline, and dementia.
The study, led by M. Arfan Ikram, MD, was published in the January issue of Stroke.
The investigators speculate that, based on the study's findings, it is possible that GFR provides a better marker than concomitantly measured cardiovascular risk factors.
However, they add, more research to elucidate the exact mechanisms underlying the association of GFR with cerebral small vessel disease is required to confirm this hypothesis.
"Given that cerebral small vessel disease is related to an increased risk of stroke, cognitive decline, and dementia, our data provide important information in addition to the known risk of adverse cardiac outcomes in persons with poor kidney function. Thus, our study further emphasizes the importance of identifying those with subclinical kidney disease," they write.
Marginal Change After Risk-Factor Adjustment
Designed to examine age-related brain abnormalities on magnetic resonance imaging (MRI), the cross-sectional study, known as the Rotterdam Scan Study (RSS), is a substudy of the Rotterdam Study, a large population-based investigation of the prevalence, incidence, and determinants of chronic disease in the elderly.
The investigation looked at 484 subjects between the ages of 60 and 90 years who were free of dementia at the study outset and who underwent MRI scans and had their GFR measured using the Cockcroft-Gault equation.
Global, lobar, and deep volumes of gray and white matter and volume of WML were measured using automated MRI analysis. Lacunar infarcts were rated visually.
Blood glucose level, blood pressure, cholesterol, CRP, and homocysteine were measured in each participant. Subjects were also screened for a history of myocardial infarction and smoking.
The investigators found that subjects in the lowest quartile of kidney function had smaller brain volumes. However, they noted that this smaller brain volume was not attributable to smaller gray-matter volume but rather to smaller total and normal WMV.
They found no association between GFR and either lobar or deep gray-matter volume.
The authors report that, after adjustment for cardiovascular risk factors, the associations were marginally attenuated, but GFR was still related to volume of WML, to deep WMV, and to brain volume.
Collaboration Needed
In an accompanying editorial, Stephen L. Seliger, MD, MS, from the University of Maryland in Baltimore, and W.T. Longstreth Jr, MD, MPH, from the University of Washington in Seattle, note that the study adds to a growing body of evidence supporting a link between vascular disease of the kidney and the brain.
However, they add, at this point the underlying mechanisms are unclear.
"Understanding the interplay of vascular disease in these 2 organs holds the promise of finding novel means to reduce the risk of impaired function, especially in the brain. The path to this understanding begins with the type of study reported by Ikram and colleagues and requires the continued collaboration of nephrologists and neurologists," they write.
The study was supported by the Health Research and Development Council and the Netherlands Organization for Scientific Research.
Stroke. 2008; 39:55-61 Abstract, 5-6. Abstract