within the glomerular capillaries, which may slow (but not stop) progression of the disease. Three classes of diabetes medications – GLP-1 agonists, DPP-4 inhibitors, and SGLT2 inhibitors– are also thought to slow the progression of diabetic nephropathy. Diabetic nephropathy is the most common cause of end-stage renal disease and is a serious complication that affects approximately one quarter of adults with diabetes in the United States. Affected individuals with end-stage kidney disease often require hemodialysis and eventually kidney transplantation to replace the failed kidney function. Diabetic nephropathy is associated with an increased risk of death in general, particularly from cardiovascular disease. Signs and symptoms The onset of symptoms is 5 to 10 years after the disease begins. A usual first symptom is frequent urination at night: nocturia. Other symptoms include tiredness, headaches, a general feeling of illness, nausea, vomiting, frequent daytime urination, lack of appetite, itchy skin, and leg swelling. The clinical presentation of diabetic nephropathy (DN) is characterized by proteinuria (protein in the urine), hypertension and progressive loss of kidney function. The process may be initially indolent, making regular screening for diabetic nephropathy in patients with diabetes mellitus of great importance. Risk factors Not all patients with diabetes go on to develop diabetic nephropathy. The main risk factors that increase the likelihood of developing diabetic nephropathy are: Poor control of blood glucose Uncontrolled high blood pressure Type 1 diabetes mellitus, with onset before age 20 Past or current cigarette use A family history of diabetic nephropathy- certain genes have been identified that are associated with DN. ( However, no direct correlation has been established yet. One of these genes is APOL1, which has been found to be associated with nephropathy in African American individuals.) Certain racial groups (African Americans, Mexican Americans, and Pima Indians are at higher risk). Pathophysiology The disease progression of diabetic nephropathy involves various clinical stages: hyperfiltration, microalbuminuria, macroalbuminuria, nephrotic proteinuria to progressive chronic kidney disease leading to end-stage renal disease (ESRD). The damage is exerted on all compartments of the kidney: the glomerulus, the renal tubules, the vasculature (afferent and efferent renal arterioles) and the interstitium. Renal fibrosis is the final common pathway of DN. This fibrosis is a product of multiple mechanisms including renal hemodynamic changes, glucose metabolism abnormalities associated with oxidative stress as well as inflammatory processes and an overactive renin-angiotensin-aldosterone system (RAAS). The pathophysiology of diabetic nephropathy is thought to involve an