Aberrant cytokines/chemokines production correlate with proteinuria in patients with overt diabetic nephropathy

Background: Diabetic nephropathy (DN) occurs in 20% to 30% of all patients with type 2 diabetes mellitus (DM) and is the most common cause of end-stage renal disease. However, the definite pathogenesis, especially the role of immune response, is still unclear. Methods: We studied the production and expression of Th1 (IFN-γ, IL-2R), Th2 (IL-4, IL-10), proinflammatory cytokines (IL-1β, and TNF-α), and chemokines (MCP-1, and RANTES) in patients with DN. The correlation among cytokines, chemokines, and clinical parameters were examined. Results: A patient with DN presented with longer disease duration, heavy proteinuria, and impaired renal function. Our results demonstrated increased proinflammatory cytokines, Th1 cytokines and chemokines, but not Th2 cytokines, in the plasma and urine of patients with DN as compared to patients with DM without overt nephropathy. Enhanced cytokine/chemokine activation in DN was also demonstrated by positive immunohistochemical staining of kidney tissue. We found a positive correlation between daily protein loss and plasma IFN-γ and IL-2R, and urinary MCP-1, as well as a negative correlation between creatinine clearance and plasma TNF-α and urinary MCP-1. Conclusions: There were aberrant cytokines/chemokines production correlated with the degree of proteinuria in patient with overt DN and gross proteinuria. Inflammation may be important in the pathogenesis of DN.