Farid Nakhoul, Nakhoul Nakhoul, Nadia Thaucho, Evgeny Farber, Hao Zhang, Mohamed Awawde, Adi Francis and Inbal Dahan
Diabetes Mellitus (DM) is metabolic disease associated with hyperlipidemia and arterial hypertension that are known as major risk factors for coronary heart disease. Diabetic complications are related to increased oxidative stress due to elevated glucose levels in the plasma. DM patients suffer from higher incidence of micro vascular complications such as Diabetic Nephropathy (DN). DN is the leading cause of End Stage Renal Disease (ESRD) and accounts for approximately 40% of all patients who require replacement therapy. Recently, the proximal tubular damage caused by increased deposition of iron in the lysosomes accompanied with oxidative stress, was described as another mechanism involved in the pathogenesis of DN. The well-known risk factors for DN are uncontrolled glucose levels, genetic factors such as Haptoglobin (Hp) and Angiotensin Converting Enzyme (ACE) genes polymorphism. Despite the availability of various drugs for DN such as converting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARB) and renin inhibitors (RI), 40% of type 2 DM (T2D) patients will develop ESRD. Hence, the aim of this review is to understand the importance of klotho protein and vitamin D in the pathogenesis of DN and as a potential future target for treatment.