Evolution of treatment for diabetic nephropathy: historical progression from RAAS inhibition and onward.
ABSTRACT The past 2 decades have brought rapid advances in treatment options for chronic kidney disease; however, even with the best treatment, the decline of renal function and progression to end-stage renal disease (ESRD) continues in a significant number of patients. The prognosis of patients with diabetes and ESRD is grim, with < 50% of patients surviving beyond 5 years after diagnosis. Therefore, early recognition and optimal use of available interventions are essential, and research into newer therapeutic targets is needed. This article will review recent advances in our understanding of renal pathophysiology, summarize the evidence to date supporting current treatment options for diabetic nephropathy, and highlight new options that lie on the horizon for the treatment of diabetic kidney disease.
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ABSTRACT: There is no cure for diabetic nephropathy and the molecular mechanisms underlying disease aetiology remain poorly understood. While current paradigms for clinical management of diabetic nephropathy are useful in delaying disease onset and preventing its progression, they do not do so for a significant proportion of diabetic individuals, who eventually end up developing renal failure. Thus, novel therapeutic targets are needed for the treatment and prevention of the disease. MicroRNAs (miRNAs), a class of non-coding RNAs that negatively regulate gene expression, have recently been identified as attractive targets for therapeutic intervention. It is widely recognised that dysregulation of miRNA expression or action contributes to the development of a number of different human diseases, and evidence of a role for miRNAs in the aetiology of diabetic nephropathy is emerging. The discovery that modulation of miRNA expression in vivo is feasible, combined with recent results from successful clinical trials using this technology, opens the way for future novel therapeutic applications. For instance, inhibition of miRNAs that are commonly upregulated in diabetic nephropathy decreases albuminuria and mesangial matrix accumulation in animal models, suggesting that a therapeutic agent against these molecules may help to prevent the development of diabetic nephropathy. Certain challenges, including the development of safe and reliable delivery systems, remain to be overcome before miRNA-based therapeutics become a reality. However, the findings accumulated to date, in conjunction with newly emerging results, are expected to yield novel insights into the complex pathogenesis of diabetic nephropathy, and may eventually lead to the identification of improved therapeutic targets for treatment of this disease.Diabetologia 01/2012; · 6.81 Impact Factor