Tapping the potential of metabolomics, an emerging field focused on the chemical processes of metabolism, researchers at the University of California (UC), San Diego School of Medicine have identified a new and pivotal player in diabetic kidney disease. The study, published online on July 22, 2015 in the Journal of the American Society of Nephrology, also clarifies a central mechanism of action in diabetic kidney disease that is generating considerable excitement among researchers and the biopharmaceutical community. 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. "Our study further illuminates the role of NOX proteins, in particular NOX4, in mediating diabetes-associated kidney dysfunction and identifies fumarate, a product of the TCA (tricarboxylic acid) and urea cycles, as a key link in the metabolic pathways underlying diabetic kidney disease," said senior author Kumar Sharma, M.D., a Professor of Medicine and Director of the Center for Renal Translational Medicine at UC San Diego School of Medicine. By pinpointing fumarate, Dr. Sharma added, the research team has also discovered a new, and potentially better, biomarker for diagnosing and monitoring chronic diabetic kidney disease. Young-Hyun You, Ph.D., a project scientist in the Center for Renal Translational Medicine, was first author on the study. The article is titled “Metabolomics Reveals a Key Role for Fumarate in Mediating the Effects of NADPH Oxidase 4 in Diabetic Kidney Disease.” 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.
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