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New pharmacological treatments for improving renal outcomes in diabetes

Abstract

Diabetic nephropathy is the most common and most rapidly growing cause of end-stage renal failure in developed countries. Diabetic nephropathy results from complex interactions between genetic, metabolic and hemodynamic factors. Improvements in our understanding of the pathogenesis of fibrosis associated with diabetic kidney disease have led to the identification of several novel targets for the treatment of diabetic nephropathy. Albuminuria is a useful clinical marker of diabetic nephropathy, as it can be used to predict a decline in renal function. A reduction in albuminuria might not, however, be reflective of a protective effect of therapies focused on ameliorating renal fibrosis. Although new strategies for slowing down the progression of several types of renal disease have emerged, the challenge of arresting the relentless progression of diabetic nephropathy remains. In this Review, we discuss novel pharmacological approaches that aim to improve the renal outcomes of diabetic nephropathy, including the use of direct renin inhibitors and statins. We also discuss the promise of using antifibrotic agents to treat diabetic nephropathy. The need for novel biomarkers of diabetic nephropathy is also highlighted.

Key Points

  • Albuminuria is a widely used marker of loss of renal function, but additional markers of the progression of diabetic nephropathy are needed

  • Preliminary evidences supports a role for the direct renin inhibitor aliskiren in the treatment of diabetic nephropathy

  • Further experimental studies and clinical trials are urgently needed to determine whether statin administration slows the progression of diabetic nephropathy

  • The efficacy of novel agents that aim to control renal fibrosis, such as anti-TGF-β antibodies and pirfenidone, are being investigated in the treatment of diabetic nephropathy

  • Improved understanding of genetic susceptibility to diabetic nephropathy and the discovery of new biomarkers may in the future enable the development of individualized therapies that prevent the development of diabetic nephropathy or slow its progression

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Figure 1: The renin–angiotensin system and potential therapeutic strategies to inhibit the progression of diabetic nephropathy.
Figure 2: Pathways through which type 1 and type 2 diabetes can cause renal damage, and the effects of known and experimental therapeutics on these pathways.

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Declèves, AE., Sharma, K. New pharmacological treatments for improving renal outcomes in diabetes. Nat Rev Nephrol 6, 371–380 (2010). https://doi.org/10.1038/nrneph.2010.57

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