Relation of Albuminuria to Coronary Microvascular Function in Patients With Chronic Kidney Disease Sari Imamura, MD, Kumiko Hirata, MD, PhD*, Makoto Orii, MD, Kunihiro Shimamura, MD, Yasutsugu Shiono, MD, Kohei Ishibashi, MD, PhD, Takashi Tanimoto, MD, PhD, Takashi Yamano, MD, PhD, Yasushi Ino, MD, PhD, Hironori Kitabata, MD, PhD, Tomoyuki Yamaguchi, MD, PhD, Takashi Kubo, MD, PhD, Atsushi Tanaka, MD, PhD, Toshio Imanishi, MD, PhD, and Takashi Akasaka, MD, PhD The relation between albuminuria and coronary microvascular function in patients with chronic kidney disease (CKD) has not been fully investigated. Therefore, we sought to assess whether albuminuria is associated with coronary flow velocity reserve (CFVR) impairment in patients with CKD. Coronary flow study was prospectively performed in 175 patients with CKD. CFVR of the left anterior descending artery was measured to evaluate coronary microvascular function using transthoracic echocardiography. We divided the patients into 5 groups according to the stages of CKD and analyzed the effect of albuminuria. CFVR gradually decreased with an increase in CKD stages. CFVR in patients with albuminuria was lower than those without albuminuria. In groups with CKD stages 2 and 3, the patients with albuminuria showed lower CFVR than those without albuminuria. Multiple logistic regression analysis revealed that albuminuria, age, and gender were independently associated with CFVR impairment. Of these factors, albuminuria was the most powerful predictor with the risk ratio of 12.4 for CFVR impairment. In conclusion, the more the CKD stages progressed, the more severe CFVR was impaired. Albuminuria was associated with CFVR impairment in patients with CKD; even in mild-to-moderate CKD, patients with albuminuria showed further reduced coronary vasodilator capacity. Ó 2014 Elsevier Inc. All rights reserved. (Am J Cardiol 2014;113:779e785) Patients with impaired glomerular filtration rate (GFR) are known to be at high risk for adverse cardiovascular events.1 In contrast, albuminuria is another major factor to define renal disease; in fact, albuminuria is also a potent independent marker of cardiovascular risk.2,3 Experimental evidence also suggests that microvascular endothelial dysfunction attributed by albuminuria participates in the mechanisms that lead to progression of atherosclerosis.4,5 Coronary flow velocity reserve (CFVR) has been considered as a functional diagnostic index for coronary stenosis. In patients with angiographically normal arteries, CFVR can be a marker of microvascular function.6 Reduced CFVR was observed in patients with impaired GFR by positron emission tomography.7 In addition, albuminuria was related to decreased CFVR by Doppler guide wire in small cohort.8 In consideration of these studies, coronary microvascular function may help to elucidate a link between renal dysfunction and cardiovascular disease. We sought to determine the influence of impaired GFR and albuminuria on coronary microvascular function in patients with chronic kidney disease (CKD) by transthoracic Doppler echocardiography.

Department of Medicine, Wakayama Medical University, 811-1 Kimiidera, Wakayama City, Japan. Manuscript received August 19, 2013; revised manuscript received and accepted November 12, 2013. See page 784 for disclosure information. *Corresponding author: Tel: (þ81) 73-447-2300; fax: (þ81) 73-4460631. E-mail address: [email protected] (K. Hirata). 0002-9149/14/$ - see front matter Ó 2014 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.amjcard.2013.11.026

Methods We prospectively recruited 175 patients with CKD, which is defined as either kidney damage or GFR