International Journal of Nephrology around 30–40% of the subjects were receiving medication for hypertension [8, 9], which potentially aﬀects the AI and PWV [10]. Thus, the present study was conducted in subjects who were not receiving any medications for either cardiovascular disease or for risk factors and demon- strated that proteinuria was associated with an increased brachial-ankle PWV, radial AI, and SBP2, whereas impaired eGFR was associated with only increase of the brachial- ankle PWV. Therefore, proteinuria may be associated with vascular damage of the central and peripheral arteries, and impaired GFR may be associated with vascular damage only of the large- to middle-sized arteries in healthy subjects. Recent prospective studies have demonstrated that in- creased stiﬀness of the larger arteries, as assessed by the carotid-femoral PWV, or of the large- to middle-sized arteries, as assessed by the brachial-ankle PWV, is a risk factor for the progressive decline of the GFR or the new onset of microalbuminuria [8, 15–17]. On the other hand, only the Framingham study has been conducted to evaluate the clinical signiﬁcance of abnormal central hemodynamics in predicting the future incidence of CKD or microalbumin- uria; however, no clinical signiﬁcance of these variables could be found in this study [8]. However, kidney has luxury blood ﬂow because of the low resistance to blood ﬂow, therefore, small arterial vessels in the kidney are exposed to high- pressure ﬂuctuations, especially in cases with elevated central blood pressure [18]. Thus, a further prospective study is proposed to examine whether abnormal central hemody- namics might be a predictor of the progression of glomerular damage, new onset of proteinuria, and/or the aggravation of proteinuria. The present study had some limitations. First, persistent proteinuria is one of the criteria for the diagnosis of CKD, but in the present study, only the results of spot proteinuria as assessed by the urinary dipstick test were avail- able. Second, while the urinary microalbumin-to-creatinine excretion ratio is another recommended parameter for estimating the severity of renal dysfunction [8, 16], we did not measure this parameter. Third, brachial-ankle PWV is primarily a marker of stiﬀness of the aorta and middle- sized arteries and closely associated with not only the aortic PWV, as assessed by a direct catheter method, but also with the carotid-femoral PWV [11, 19], the most well- established index for the measurement of aortic stiﬀness [4, 5, 8]. 5. Conclusion In middle-aged healthy Japanese subjects, who were not receiving medications for cardiovascular diseases or their risk factors, proteinuria was found to be an independent risk factor for abnormal central hemodynamics and increased stiﬀness of the large- to middle-sized arteries. On the other hand, moderate-to-severe impairment of the eGFR (15 to 59 mL/min per 1.73 m2) was only associated with increased arterial stiﬀness. 5 Acknowledgment This study was supported in part by a fund awarded by OMRON Health Care Company (Kyoto, Japan) to Professor A. Yamashina. References [1] F. C. Brosius III, T. H. Hostetter, E. Kelepouris et al., “Detec- tion of chronic kidney disease in patients with or at increased risk of cardiovascular disease: a science advisory from the American Heart Association Kidney and Cardiovascular Dis- ease Council; the Councils on High Blood Pressure Research, Cardiovascular Disease in the Young, and Epidemiology and Prevention; and the Quality of Care and Outcomes Research Interdisciplinary Working Group,” Circulation, vol. 114, no. 10, pp. 1083–1087, 2006. [2] E. Imai, M. Horio, T. Watanabe et al., “Prevalence of chronic kidney disease in the Japanese general population,” Clinical and Experimental Nephrology, vol. 13, no. 6, pp. 621–630, 2009. [3] E. Imai, M. Horio, K. Iseki et al., “Prevalence of chronic kidney disease (CKD) in the Japanese general population predicted by the MDRD equation modiﬁed by a Japanese coeﬃcient,” Clinical and Experimental Nephrology, vol. 11, no. 2, pp. 156– 163, 2007. [4] C. Vlachopoulos, K. Aznaouridis, M. F. O’Rourke, M. E. Safar, K. Baou, and C. Stefanadis, “Prediction of cardiovascular events and all-cause mortality with central haemodynamics: a systematic review and meta-analysis,” European Heart Journal, vol. 31, no. 15, pp. 1865–1871, 2010. [5] C. Vlachopoulos, K. Aznaouridis, and C. Stefanadis, “Pre- diction of cardiovascular events and all-cause mortality with arterial stiﬀness. A systematic review and meta-analysis,” Journal of the American College of Cardiology, vol. 55, no. 13, pp. 1318–1327, 2010. [6] G. M. London, J. Blacher, B. Pannier, A. P. Gue´rin, S. J. Marchais, and M. E. Safar, “Arterial wave reﬂections and survival in end-stage renal failure,” Hypertension, vol. 38, no. 3, pp. 434–438, 2001. [7] J. Blacher, A. P. Guerin, B. Pannier, S. J. Marchais, M. E. Safar, and G. M. London, “Impact of aortic stiﬀness on survival in end-stage renal disease,” Circulation, vol. 99, no. 18, pp. 2434– 2439, 1999. [8] A. Upadhyay, S. J. Hwang, G. F. Mitchell et al., “Arterial stiﬀness in mild-to-moderate CKD,” Journal of the American Society of Nephrology, vol. 20, no. 9, pp. 2044–2053, 2009. [9] M. M. H. Hermans, R. Henry, J. M. Dekker et al., “Estimated glomerular ﬁltration rate and urinary albumin excretion are independently associated with greater arterial stiﬀness: the Hoorn study,” Journal of the American Society of Nephrology, vol. 18, no. 6, pp. 1942–1952, 2007. [10] R. Asmar, “Eﬀects of pharmacological intervention on arterial stiﬀness using pulse wave velocity measurement,” Journal of the American Society of Hypertension, vol. 1, no. 2, pp. 104– 112, 2007. [11] H. Tomiyama, H. Hashimoto, H. Tanaka et al., “Continuous smoking and progression of arterial stiﬀening: a prospective study,” Journal of the American College of Cardiology, vol. 55, no. 18, pp. 1979–1987, 2010. [12] M. Odaira, H. Tomiyama, C. Matsumoto et al., “Association of serum cystatin C with pulse wave velocity, but not pressure wave reﬂection, in subjects with normal renal function or mild