Abstrait

New therapeutic agents for diabetic kidney disease

Varun Agrawal, Sani Haider Kizilbash and Peter A McCullough

Diabetic kidney disease continues to be the leading cause of end-stage renal disease despite therapies targeted towards glycemic and blood pressure control, and drugs that block the renin–angiotensin–aldosterone system. New therapeutic agents are being studied to retard the progression of kidney damage due to diabetes. Glycosaminoglycans (e.g., sulodexide) target the glomerular basement membrane and have been shown to reduce albuminuria in multiple Phase II clinical trials. Inhibitors of advanced glycation end-product formation (e.g., pyridoxamine) reduce the renal accumulation of these pathogenic substrates with mixed clinical efficacy results. Protein kinase C inhibitors (e.g., ruboxistaurin) reduce renal damage from overexpression of this kinase, and have shown encouraging results in Phase II studies. Iron chelators, as antioxidant agents, work in reducing cellular damage by reactive oxygen species that are part of common final pathways in diabetic kidney disease. Other agents discussed in this review target multiple molecular pathways in diabetic kidney disease. If successfully developed, future clinical trials will evaluate the efficacy of these new drugs in slowing the progression of diabetic kidney disease.