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  • Review Article
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The pathogenesis of diabetic nephropathy

Nature Clinical Practice Endocrinology & Metabolism volume 4, pages 444–452 (2008)Cite this article

Abstract

Between 20% and 40% of patients with diabetes ultimately develop diabetic nephropathy, which in the US is the most common cause of end-stage renal disease requiring dialysis. Diabetic nephropathy has several distinct phases of development and multiple mechanisms contribute to the development of the disease and its outcomes. This Review provides a summary of the latest published data dealing with these mechanisms; it focuses not only on candidate genes associated with susceptibility to diabetic nephropathy but also on alterations in various cytokines and their interaction with products of advanced glycation and oxidant stress. Additionally, the interactions between fibrotic and hemodynamic cytokines, such as transforming growth factor β1 and angiotensin II, respectively, are discussed in the context of new information concerning nephropathy development. We touch on the expanding clinical data regarding markers of nephropathy, such as microalbuminuria, and put them into context; microalbuminuria reflects cardiovascular and not renal risk. If albuminuria levels continue to increase over time then nephropathy is present. Lastly, we look at advances being made to enable identification of genetically predisposed individuals.

Key Points

  • Microalbuminuria is not a predictor of nephropathy development in individuals with diabetes

  • Multiple mechanisms are operative in diabetes that are related to injury to the kidney and, in susceptible individuals, contribute to nephropathy development

  • Defects in nephrin and podocin are central to the development of macroalbuminuria and associated with nephropathy progression

  • Abnormally high concentrations of lipids contribute to β-cell injury and development of albuminuria

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Acknowledgements

Charles P Vega, University of California, Irvine, CA, is the author of and is solely responsible for the content of the learning objectives, questions and answers of the Medscape-accredited continuing medical education activity associated with this article.

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Authors and Affiliations

  1. S Dronavalli is Instructor of Medicine and I Duka is a Fellow in the Department of Medicine, and GL Bakris is Director of the Hypertensive Diseases Unit, Section of Endocrinology, Diabetes and Metabolism, Pritzker School of Medicine, University of Chicago, IL, USA.,

    Suma Dronavalli, Irena Duka & George L Bakris

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  1. Suma Dronavalli
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  2. Irena Duka
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  3. George L Bakris
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Correspondence to George L Bakris.

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Dronavalli, S., Duka, I. & Bakris, G. The pathogenesis of diabetic nephropathy. Nat Rev Endocrinol 4, 444–452 (2008). https://doi.org/10.1038/ncpendmet0894

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