Circulating TNF receptor 2 is associated with the development of chronic kidney disease in non-obese Japanese patients with type 2 diabetes Yoshio Izumi a , Daisuke Yabe b , Ataru Taniguchi c , Mitsuo Fukushima d, *, Yoshikatsu Nakai e , Masaya Hosokawa f , Takahide Okumura g , Kazuko Nin h , Kazunari Matsumoto i , Fusanori Nishimura j , Shoichiro Nagasaka k , Yutaka Seino b a Department of Internal Medicine, Osaka North Postal Services Agency Hospital, Osaka, Japan b Division of Diabetes, Clinical Nutrition and Endocrinology, Kansai Electric Power Hospital, Osaka, Japan c Division of Diabetes and Endocrinology, Kyoto Preventive Medical Center, Kyoto, Japan d Division of Clinical Nutrition and Internal Medicine, Okayama Prefectural University, Okayama, Japan e Kyoto Institute of Health Sciences, Kyoto, Japan f Faculty of Human Sciences, Tezukayamagakuin University, Osaka, Japan g Department of Pharmacy, Saiseikai Nakatsu Hospital, Osaka, Japan h Human Health Sciences, Graduate School of Medicine, Kyoto University, Japan i Diabetes Center, Sasebo Chuo Hospital, Nagasaki, Japan j Department of Dental Science for Health Promotion, Hiroshima University Graduate School of Biomedical Sciences, Hiroshima, Japan k Division of Endocrinology and Metabolism, Jichi Medical University, Tochigi, Japan d i a b e t e s r e s e a r c h a n d c l i n i c a l p r a c t i c e x x x ( 2 0 1 3 ) x x x – x x x a r t i c l e i n f o Article history: Received 14 September 2012 Received in revised form 26 October 2012 Accepted 7 November 2012 Keywords: eGFR Tumor necrosis factor Type 2 diabetes a b s t r a c t Aims: Chronic low-grade inflammation and/or obesity are suggested to induce chronic kidney disease (CKD) in patients with type 2 diabetes. This cross-sectional study was performed to investigate the relationship between inflammatory biomarkers and CKD in non-obese patients with type 2 diabetes. Methods: 106 non-obese Japanese patients with type 2 diabetes were recruited for the measurement of GFR, TNF, HMW adiponectin, leptin, hsCRP and some variables including urinary albumin. BMI, serum creatinine, and urinary albumin levels were 22.2 Æ 0.2 kg/m 2 (17.1–24.9 kg/m 2 ), 0.76 Æ 0.02 mg/dl (0.39–1.38 mg/dl), 40.4 Æ 4.3 mg/gCr (1.6–195.0 mg/gCr), respectively. They were stratified into two groups based on the value of eGFR: low eGFR (eGFR < 60 ml/min/1.73 m 2 ) and normal eGFR (eGFR > 60 ml/min/1.73 m 2 ). Logistic regres- sion analysis was used for statistical analysis. Results: Whereas univariate logistic regression analysis showed that gender, diabetes duration, triglyceride, HDL cholesterol, uric acid, urinary albumin, and soluble TNF receptors (sTNF-R1, sTNF-R2) are associated with the development of stage 3 CKD, multivariate logistic regression analysis revealed that sTNF-R2 (Odds ratio 1.003, 95% confidence interval 1.000 to 1.005, P = 0.030) showed significant associations with the development of stage 3 CKD. Conclusions: Circulating TNF receptor 2 is an independent risk factor for CKD in non-obese Japanese patients with type 2 diabetes. # 2013 Published by Elsevier Ireland Ltd. * Corresponding author at: Division of Clinical Nutrition and Internal Medicine, Department of Nutritional Science, Faculty of Health and Welfare Science, Okayama Prefectural University, 111, Kuboki Soja, Okayama 719-1197, Japan. Tel.: +81 866 94 2151; fax: +81 866 94 2151. E-mail address: Fukushima7788@yahoo.co.jp (M. Fukushima). Abbreviations: BMI, body mass index; eGFR, estimated GFR; GFR, glomerular filtration rate; HMW, high molecular weight; hsCRP, high sensitive C-reactive protein; TNF, tumor necrosis factor; sTNF-R, soluble TNF receptor. DIAB-5652; No. of Pages 6 Please cite this article in press as: Izumi Y, et al. Circulating TNF receptor 2 is associated with the development of chronic kidney disease in non- obese Japanese patients with type 2 diabetes. Diabetes Res Clin Pract (2013), http://dx.doi.org/10.1016/j.diabres.2012.11.002 Contents available at Sciverse ScienceDirect Diabetes Research and Clinical Practice journal homepage: www.elsevier.com/locate/diabres 0168-8227/$ – see front matter # 2013 Published by Elsevier Ireland Ltd. http://dx.doi.org/10.1016/j.diabres.2012.11.002