Fibrates: therapeutic potential for diabetic nephropathy?

Despite intensive glucose-lowering treatment and advanced therapies for cardiovascular risk factors, such as hypertension and dyslipidaemia, diabetes mellitus with its macro- and microvascular complications remains a major health problem. Especially diabetic nephropathy is a leading cause of morbidity and mortality, and its prevalence is increasing. Peroxisome proliferator-activated receptor-α (PPAR-α), a member of a large nuclear receptor superfamily, is expressed in several tissues including the kidney. Recently, experimental data have suggested that PPAR-α activation plays a pivotal role in the regulation of fatty acid oxidation, lipid metabolism, inflammatory and vascular responses, and might regulate various metabolic and intracellular signalling pathways that lead to diabetic microvascular complications. This review examines the role of PPAR-α activation in diabetic nephropathy and summarises data from experimental and clinical studies on the emerging therapeutic potential of fibrates in diabetic nephropathy.