PubMedCrossRef 24. Ohkita M, Takaoka M, Matsumura Y. Drug discovery for overcoming chronic kidney disease (CKD): the endothelin ET B receptor/nitric oxide system functions as a protective factor in CKD. J Pharmacol Sci. 2009;109:7–13.PubMedCrossRef 25. Ishizawa K, Yamaguchi K, Horinouchi Y, Fukuhara Y, Tajima S, Hamano S, et al. Drug discovery for overcoming chronic kidney disease (CKD): development of drugs on endothelial cell protection for overcoming CKD. J Pharmacol Sci. 2009;109:14–9.PubMedCrossRef

26. Yamagata K, Makino H, Akizawa T, Iseki K, Itoh Smoothened Agonist in vivo S, Selleckchem U0126 Kimura K, et al. Design and methods of a strategic outcome study for chronic kidney disease: frontier of renal outcome modifications in Japan. Clin Exp Nephrol. 2010;14:144–51.PubMedCrossRef

27. Peralta CA, Shlipak MG, Judd S, Cushman M, McClellan W, Zakai NA, et al. Detection of chronic kidney disease with creatinine, cystatin C, and urine albumin-to-creatinine ratio and association with progression to end-stage renal disease and mortality. JAMA. 2011;305:1545–52.PubMedCentralPubMedCrossRef”
“Introduction Chronic kidney disease (CKD) is a worldwide public health problem [1, 2]. It has been reported that the prevalence of CKD is 13 % in the United States [3], 10–13 % in European countries [4, 5], 13 % in Japan [6] and 12–13 % in China [7]. Of all CKD patients, those with proteinuria have been shown to have a higher risk of developing cardiovascular disease (CVD) [8], as well as end-stage renal disease Tariquidar chemical structure (ESRD) Clostridium perfringens alpha toxin [9]. Although a renal biopsy is a useful diagnostic procedure to elucidate the pathogenesis in proteinuric patients, we sometimes encounter those who do not fit the diagnostic criteria for any known primary or secondary glomerular diseases. The pathogenesis and pathophysiology of these CKD patients have not been sufficiently elucidated. On the other hand, previous experimental and clinical studies demonstrated that glomerular hypertrophy

(GH) plays an important role in the progression of glomerular injury [10, 11]. We recently reported that a low glomerular density (GD) associated with GH might be a characteristic histological finding of patients with obesity-related glomerulopathy (ORG) [12]. We hypothesized that the GD, GH and obesity could be the characteristic findings of the proteinuric CKD patients without known glomerular diseases. To investigate this hypothesis, we carried out an investigation to explore the pathogenic role of GD, the glomerular volume (GV) and obesity in those patients. Subjects and methods Patient selection Of the 990 Japanese patients who underwent a renal biopsy at our institute from 1995 through 2000, because they presented with persistent urine abnormalities, such as proteinuria, we excluded 947 patients with known primary or secondary glomerular diseases, i.e.