Diabetic kidney disease is the leading cause of end-stage kidney disease, the eighth leading cause of death in the United States and a major risk factor for cardiovascular disease. An estimated 26 million American adults have chronic kidney disease, often requiring dialysis or a kidney transplant. Researchers at University of California, San Diego School of Medicine have identified a new and pivotal player in diabetic kidney disease. The mechanism, involving the NADPH (nicotinamide adenine dinucleotide phosphate) oxidase (NOX) proteins, NOX1 and NOX4, is now the subject of a phase II clinical trial for the treatment of diabetic kidney disease. The researchers tested mice engineered to overproduce NOX4 and identified that overproduction of NOX4 in kidney cells, called podocytes, produced many of the features of diabetic kidney disease. The diabetic mice were then given a compound known as GKT137831, a NOX 1/4 inhibitor developed by Swiss pharmaceutical Genkyotex SA, and presently in phase II clinical trials for diabetic kidney disease, also known as diabetic nephropathy.