New Insights on Diabetic Nephropathy

Diabetic Nephropathy (DN) is a long-standing complication of Diabetes Mellitus (DM) and is responsible for more than 40% of end-stage renal disease cases in developed countries. The pathogenesis of DN is multifactorial inclusing genetic and environmental factors. Traditional risk factors and glycemic control are important but inadequate for predicting the incidence and severity of DN. Different pathways are involved in the pathogenesis of DN. Hyperglycemia accelerates oxidative stress with increased production of free radicals. Reactive oxygen species, particularly those derived from iron, have been implicated in the increase of oxidative stress injury in the Proximal Convolute Tubules and glomeruli with progression of DN. Polymorphic genetic loci encoding variants in enzymes protecting against iron-induced oxidative stress and apoptosis, serve as potential susceptibility determinants for the development of DN. The major function of the Haptoglobin protein is to bind and modulate the fate of extra-corpuscular hemoglobin and its iron cargo. Since Iron plays a major role in the development of DN it may be a therapeutic target for slowing the nephropathy progression. A combination of glycemic and blood pressure control, utilizing renin angiotensin-aldosterone system RAAS blockers, has been a mainstay of treatment to slow DN progression. Inhibition of RAAS plays a pivotal role in treatment of chronic diabetic kidney diseases. However, reversal of the course of DN or at least long-term stabilization of renal function is often difficult to achieve, and many patients still progress to end-stage renal disease. In the current review we suggested some integrated mechanisms involved in DN progression.