Have we reached the limits for the treatment of diabetic nephropathy?

INTRODUCTION: The prevalence of diabetic nephropathy is increasing as a consequence of the global epidemic of diabetes, and the complications of diabetic nephropathy are unsurprisingly legion. Blockade of the renin-angiotensin-aldosterone system (RAAS) has formed the mainstay of management, but despite this, most individuals will suffer premature cardiovascular events, and many will progress to end-stage renal disease. Given the heterogeneity of pathologies, it is perhaps naïve to hope that blocking a single neurohormonal pathway will protect against the myriad of pathogenetic mechanisms that conspire to cause the injuries seen with diabetes. Chronic hyperglycaemia and resulting advanced glycation end products form a mechanistic axis, which appears central to many of the pathways that lead to diabetic nephropathy. Treatment with pyridoxamine (an inhibitor of advanced glycation end-products) may represent a strategy to counter these injurious pathways. AREAS COVERED: In this review, the authors explore pyridoxamine and other emerging therapeutic agents in the battle against diabetic nephropathy. The authors also provide their perspectives on the field and potential future directions. EXPERT OPINION: Although issues around validity of surrogate markers and clinical end points have complicated trial data in the field, currently available evidence is not persuasive as regards the clinical application of these agents. There remains a clear and growing need for emerging therapeutics to be used in combination with RAAS blocking agents.