Association of biomarkers of inflammation and oxidative stress with the risk of chronic kidney disease in Type 2 diabetes mellitus in North Indian population ☆ Stuti Gupta, Jasvinder K. Gambhir ⁎, OP Kalra, Amar Gautam, Kirtikar Shukla, Mohit Mehndiratta, Sunil Agarwal, Rimi Shukla Departments of Biochemistry and Medicine, University College of Medical Sciences (University of Delhi) & GTB Hospital, Delhi, 110095 India abstract article info Article history: Received 15 April 2013 Received in revised form 11 July 2013 Accepted 21 July 2013 Available online 6 September 2013 Keywords: Chronic kidney disease Type 2 DM Oxidative stress Inflammation Chronic kidney disease (CKD) is a major cause of morbidity and mortality worldwide. It results from diverse etiologies, diabetes being a frontrunner amongst them. Type 2 diabetes mellitus (DM) is being increasingly recognized as a proinflammatory state with increased oxidative stress which enormously increases the risk of micro and macro vascular diseases. This study was planned to explore the possible association between tumor necrosis factor-alpha (TNF-α), urinary monocyte chemoattractant protein-1 (uMCP-1), high- sensitivity C-reactive protein (hsCRP) and parameters of oxidative stress in patients with Type 2 diabetes mellitus (DM) and diabetic chronic kidney disease (DM–CKD). Fifty patients each were recruited in DM, DM–CKD and healthy control groups. Plasma TNF-α, hsCRP and uMCP-1 levels as inflammatory mediators were measured by ELISA, reduced glutathione (GSH), ferric reducing ability of plasma (FRAP) as parameters of antioxidant activity and malondialdehyde (MDA) as marker of oxidative stress, were measured spectrophotometrically. Plasma TNF-α, hsCRP and uMCP-1 were significantly higher in DM–CKD compared to DM and healthy controls. Lipid peroxidation, measured as MDA was significantly higher in patients with DM–CKD as compared to patients with DM and healthy controls. Further, antioxidant capacity of blood measured as FRAP and GSH was found to be significantly lower in patients with DM and DM–CKD as compared to healthy controls (p b 0.001). Plasma TNF-α and uMCP-1 showed a significant positive correlation with HbA 1c (r = 0.441, 0.643), hsCRP (r = 0.400, 0.584) and MDA (r = 0.423, 0.759) and significant negative correlation with GSH (R = -0.370, -0.800) and FRAP (r = -0.344, -0.684) Increased inflammatory markers viz. TNF-α, hsCRP and uMCP-1 and markers of oxidative stress i.e. increased MDA and decreased GSH and FRAP in DM–CKD suggest an important role of inflammation and oxidative stress in the pathogenesis of renal damage in diabetic patients. © 2013 Elsevier Inc. All rights reserved. 1. Introduction Type 2 diabetes mellitus (T2DM) is one of the most challenging health concerns of the 21st century. T2DM is a proinflammatory state with increased oxidative stress, predisposing the patients to macro- and micro-vascular complications. Diabetic nephropathy (DN), a microvascular complication of long term uncontrolled DM is the single most frequent cause of end-stage renal disease (ESRD) (Ritz, Rychlik, Locatelli, & Halimi, 1999), accounting for approximately 40% of new cases of ESRD every year (Kramer & Molitch, 2005). Although metabolic and hemodynamic alterations are considered the main cause of renal damage in diabetes, the accumulating evidence now indicates that immunologic and inflammatory mech- anisms also play a significant role in its development and progression (Tuttle, 2005; Mora & Navarro, 2006). Diabetics have been shown to produce excessive inflammatory cytokines such as tumor necrosis factor-alpha (TNF-α) and C-reactive protein (CRP) (Zinman, Hanley, Harris, Kwan, & Fantus, 1999), and few studies have also reported association between inflammatory biomarkers and DN (Navarro, Mora, Muros, & García, 2006; Yeo, Hwang, Park, Choi, Huh, & Kim, 2010; Lu, Randell, Han, Adeli, Krahn, & Meng, 2011; Taslipinar et al., 2011; Fernández-Real, Vendrell, García, Ricart, & Vallès, 2012). Most attention has been focused on the role of TNF-α, which is a pleiotropic proinflammatory cytokine primarily synthesized by monocytes, macrophages and T cells and plays an important role in pathogenesis of DN. Many studies in animal models have shown that intrinsic renal cells, including glomerular, mesangial, endothelial and tubular cells, are also able to produce this cytokine (Jevnikar et al., 1991; Nakamura et al., 1993; Sugimoto, Shikata, Wada, Horiuchi, & Makino, 1999; Dong, Swaminathan, Bachman, Croatt, Nath, & Griffin, 2007; Zhang, Journal of Diabetes and Its Complications 27 (2013) 548–552 ☆ Declaration of interest: The authors alone are responsible for the content and writing of the paper and there is no conflict of interest. ⁎ Corresponding author. Tel.: +91 9811641277. E-mail address: jassigambhir@yahoo.co.in (J.K. Gambhir). 1056-8727/$ – see front matter © 2013 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.jdiacomp.2013.07.005 Contents lists available at ScienceDirect Journal of Diabetes and Its Complications journal homepage: WWW.JDCJOURNAL.COM