Association of Plasma Uric Acid with Inflammatory and Oxidative Stress Markers in Diabetic Nephropathy in North Indian Population: A Case Control Study

Abstract

Introduction: Uric acid (UA), despite being a major antioxidant in human plasma, is also associated with development of diseases associated with oxidative stress. There have been few studies exploring the relationship of Plasma Uric Acid (PUA) with oxidative stress and inflammation. Aim: To analyse the association between UA and markers of oxidative stress and inflammation in diabetic nephropathy. Materials and Methods: The present case control study enrolled 100 participants and were categorized into two Groups (50 each) i.e., Type 2 Diabetes Mellitus without complication (T2DM) and Type 2 Diabetes Mellitus with Nephropathy (DN). Markers of oxidative stress like reduced Glutathione (GSH), Ferric Reducing Ability of Plasma (FRAP), Glutathione-S-Transferase (GST) and Malondialdehyde (MDA) were measured spectrophotometrically. Plasma TNF-α, hsCRP, urinary MCP-1 as markers of inflammation were estimated by ELISA. PUA was measured by uricasePAP method. Student’s t-test, pearson correlation and, linear regression were used for statistical analysis. Results: Plasma TNF-α, hsCRP, urinary MCP-1 were significantly (p<0.001) higher in DN as compared to patients with T2DM. GSH, FRAP and GST were lower (p<0.001) in DN as compared to T2DM group. However, plasma MDA was significantly higher in DN group as compared to T2DM. PUA significantly correlated negatively with GSH(r=-0.937, p<0.001), FRAP (r=-0.649, p<0.01), GST (r=-0.905, p<0.01) and positively with MDA (r=0.931, p<0.01), TNF-α (r=0.552, p<0.01), hsCRP (r=0.815, p<0.01), uMCP-1 (r=0.811, p< 0.001). In multivariate analysis, PUA was associated negatively with FRAP (Model 3:p=0.045) and GST (Model 3:p=0.44) but lost significance with GSH (Model 3:p=0.741), MDA (Model 3:p=0.884). However, PUA was associated with positively with TNF-α (Model 3:p=0.038), hsCRP (Model 3:p=0.036) and uMCP-1 (Model 3:p=0.040). Conclusion: PUA was associated negatively with FRAP, GST and positively with TNF-α, hsCRP, uMCP-1 in diabetic patients. These results suggest that UA contributes to oxidative stress and systemic inflammation.

Keywords

• chronic kidney disease
• diabetes mellitus
• inflammatory markers
• pro-oxidant