Original Contribution Chronic Kidney Disease in Patients With Lacunar Stroke Association With Enlarged Perivascular Spaces and Total Magnetic Resonance Imaging Burden of Cerebral Small Vessel Disease Lulu Xiao, MD*; Wenya Lan, MD*; Wen Sun, MD, PhD; Qiliang Dai, MD; Yunyun Xiong, MD, PhD; Ling Li, MD; Yan Zhou, MD; Ping Zheng, MD; Wenping Fan, MD; Nan Ma, MD; Zhiliang Guo, MD; Xin Chen, MD; Xia Xie, MD; Lili Xu, MD; Wusheng Zhu, MD, PhD; Gelin Xu, MD, PhD; Xinfeng Liu, MD, PhD Background and purpose—The relationship between chronic kidney disease and cerebral small vessel disease (cSVD), especially enlarged perivascular spaces (EPVS), has not been fully understood. This study aimed to investigate the association of chronic kidney disease and EPVS, as well as the total burden of cSVD on magnetic resonance imaging, expressed by the simultaneous presence of multiple markers of cSVD, among patients with first-ever lacunar stroke. Methods—Four hundred and thirteen consecutive patients were prospectively enrolled. Centrum semiovale and basal ganglia EPVS on T2-weighted magnetic resonance imaging, as well as other imaging markers of cSVD, including lacune, white matter lesions, and cerebral microbleeds, were rated using validated scales. Chronic kidney disease was defined as either reduced estimated glomerular filtration rate or the presence of proteinuria. Results—After adjustments for potential confounders by logistic regression, proteinuria and impaired estimated glomerular filtration rate were correlated with the severity of EPVS in both centrum semiovale (odds ratio [OR] 2.59; 95% confidence interval [CI] 1.19–5.64 and OR 2.37; 95% CI 1.19–4.73) and basal ganglia (OR 5.12; 95% CI 2.70–12.10 and OR 4.17; 95% CI 2.08–8.37). A similar association was also found between proteinuria and low estimated glomerular filtration rate levels and the comprehensive cSVD burden (OR 2.13; 95% CI 1.10–4.14 and OR 5.59; 95% CI 2.58–12.08). Conclusions—Proteinuria and impaired estimated glomerular filtration rate are associated with increasing EPVS severity and, furthermore, accumulated magnetic resonance imaging burden of cSVD in patients with first-ever acute lacunar stroke.   (Stroke. 2015;46:00-00. DOI: 10.1161/STROKEAHA.114.008155.) Key Words: cerebral small vessel disease ◼ enlarged perivascular spaces ◼ glomerular filtration rate ◼ proteinuria

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hronic kidney disease (CKD), as an important public health problem, affects 10% to 15% of the general adult population.1–4 It was commonly defined by a reduction in the estimated glomerular filtration rate (eGFR) or the presence of proteinuria.4 Increasing evidence links CKD to higher risk and mortality of cerebrovascular disease because both human brain and kidney are low-resistance-end arterial organs allowing continuous and passive high-volume perfusion throughout systole and diastole.5–7 Of the many pathophysiological mechanisms underlying cerebrovascular disease, small vessel microangiopathy would presumably be the type with the strongest association with impaired kidney function because

the microvasculature of both organs share anatomic and functional vasoregulatory similarities.8 Previous studies have indicated that CKD correlates with a higher prevalence of white matter hyperintensities (WMH), lacune, and cerebral microbleeds (CMBs).9–11 However, the association between CKD and enlarged perivascular spaces (EPVS), a novel marker of cerebral small vessel disease (cSVD), has not yet been clarified. Furthermore, the combined effect of these magnetic resonance imaging (MRI) markers of cSVD on impaired kidney function has never been studied. It seems rather artificial to over-reliance on one marker only while disregarding the others.12–15

Received November 23, 2014; final revision received May 27, 2015; accepted May 28, 2015. From the Department of Neurology (L.X., W.S., Q.D., Y.X., W.F., N.M., Z.G., X.C., X.X., L.X., W.Z., G.X., X.L.), Department of Radiology (L.L.), and National Clinical Research Center of Kidney Diseases (Y.Z.), Jinling Hospital, Medical School of Nanjing University, Nanjing, China; Department of Geriatric Neurology, Nanjing Brain Hospital Affiliated to Nanjing Medical University, Nanjing, China (W.L.); and Department of Medicine, Royal Melbourne Hospital, University of Melbourne (P.Z.). *Drs Xiao and Lan contributed equally. The online-only Data Supplement is available with this article at http://stroke.ahajournals.org/lookup/suppl/doi:10.1161/STROKEAHA. 114.008155/-/DC1. Reprint requests to Wusheng Zhu, MD, PhD, Department of Neurology, Jinling Hospital, Medical School of Nanjing University, 305 E Zhongshan Rd, Nanjing 210002, Jiangsu Province, China, E-mail [email protected] or Xinfeng Liu, MD, PhD, Department of Neurology, Jinling Hospital, Medical School of Nanjing University, 305 E Zhongshan Rd, Nanjing 210002, Jiangsu Province, China, E-mail [email protected] © 2015 American Heart Association, Inc. Stroke is available at http://stroke.ahajournals.org

DOI: 10.1161/STROKEAHA.114.008155

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2  Stroke  August 2015 Thus, we aimed to clarify the association of CKD with EPVS severity and the total burden of cSVD on MRI in patients with first-ever lacunar stroke.

Methods Patients We prospectively recruited patients with first-ever lacunar stroke in the department of neurology at Jingling hospital. Details of patient inclusion can be found in the online-only Data Supplement. All patients had a detailed diagnostic assessment that included neurological investigations, blood pressure measurements, MRI (unless contraindicated), blood tests, and urine tests. In this study, lacunar stroke was defined as an acute lacunar stroke syndrome with a small (maximum diameter of 15 mm), deep infarct on MRI compatible with the clinical findings, or, if no such lesion was visible, we used established criteria of specific clinical lacunar syndromes.16 Because we aimed to study patients who most likely had their stroke from local cSVD, patients with a possible cardioembolic source (most commonly atrial fibrillation or a valvular prosthesis) or large-vessel cerebrovascular disease defined as internal carotid, middle cerebral, or basilar intracranial artery stenosis >50% were excluded. Informed consent was obtained from all participants, and the study protocol was approved by the institutional Human Research Ethics Committee of Jinling Hospital.

Measurement of the eGFR and Proteinuria eGFR was calculated individually by the following Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation for the Asian population17,18: eGFR=141×min (serum creatinine/κ,1)α×max (serum creatinine/κ,1) −1.209×0.993Age×1.018 [if female], where κ was 0.7 for females and 0.9 for males, α was −0.329 for females and −0.411 for males, min was the minimum of SCr/κ or 1, and max indicated the maximum of SCr/κ or 1. A low eGFR level was defined as

Chronic Kidney Disease in Patients With Lacunar Stroke: Association With Enlarged Perivascular Spaces and Total Magnetic Resonance Imaging Burden of Cerebral Small Vessel Disease.

The relationship between chronic kidney disease and cerebral small vessel disease (cSVD), especially enlarged perivascular spaces (EPVS), has not been...
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