Abstract
Diabetes mellitus (DM) is a complex, progressive disease, which is accompanied by multiple complications. One of the major complication confronted by patients with diabetes is an increased risk of developing diabetic nephropathy (DN) that often progresses to end-stage renal disease. Pathogenesis of DN is multifactorial. The role of hyperglycemia in the pathogenesis of DN has been previously established by a number of studies. Hyperglycemia induces oxidative stress in the rat kidney and increased oxidative stress in the kidney may trigger apoptosis in renal cells in vitro by inducing DNA fragmentation and stimulating expression of apoptosis-regulatory genes. Hyperglycemia also leads to accumulation of advanced glycation end products (AGE's) in renal cortex. These AGE's play a role in the progression of DN through impairment of matrix proteins in vivo, leading to thickening of glomerular basement membrane and expansion of mesangial matrix. DN is also associated with dyslipidemia, which is characterized by higher plasma levels of total cholesterol, low-density lipoprotein and triglycerides, and lower levels of high-density lipoprotein. Reportedly, lipids may induce both glomerular and tubulointerstitial injury through mediators such as cytokines, reactive oxygen species, chemokines, and through hemodynamic changes. A growing body of evidences also suggests that transforming growth factor-beta (TGF-beta), a fibrogenic cytokine plays a key role in the development of DN. Moreover much advancement has been done to manageDN ascontrol of blood pressure, glucose, and lipids, inhibition of the rennin angiotensin system but these are inadequate to retard the progression of nephropathy.