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  • Primer
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Diabetic kidney disease

Nature Reviews Disease Primers volume 1, Article number: 15018 (2015) Cite this article

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A Correction to this article was published on 29 October 2015

Abstract

The kidney is arguably the most important target of microvascular damage in diabetes. A substantial proportion of individuals with diabetes will develop kidney disease owing to their disease and/or other co-morbidity, including hypertension and ageing-related nephron loss. The presence and severity of chronic kidney disease (CKD) identify individuals who are at increased risk of adverse health outcomes and premature mortality. Consequently, preventing and managing CKD in patients with diabetes is now a key aim of their overall management. Intensive management of patients with diabetes includes controlling blood glucose levels and blood pressure as well as blockade of the renin–angiotensin–aldosterone system; these approaches will reduce the incidence of diabetic kidney disease and slow its progression. Indeed, the major decline in the incidence of diabetic kidney disease (DKD) over the past 30 years and improved patient prognosis are largely attributable to improved diabetes care. However, there remains an unmet need for innovative treatment strategies to prevent, arrest, treat and reverse DKD. In this Primer, we summarize what is now known about the molecular pathogenesis of CKD in patients with diabetes and the key pathways and targets implicated in its progression. In addition, we discuss the current evidence for the prevention and management of DKD as well as the many controversies. Finally, we explore the opportunities to develop new interventions through urgently needed investment in dedicated and focused research. For an illustrated summary of this Primer, visit: http://go.nature.com/NKHDzg

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Figure 1: The prevalence of CKD in different populations with type 2 diabetes.
Figure 2: The central role of ROS in diabetic complications.
Figure 3: Glomerulopathy in diabetes.
Figure 4: Cellular contributors to myofibroblast recruitment and subsequent tubulointerstitial fibrosis in DKD.
Figure 5: The relationship between glycaemic control and the incidence of CKD.
Figure 6: The incidence of ESRD in patients with type 2 diabetes from the ADVANCE-ON trial.
Figure 7: The strong association between diabetic kidney disease and increased incidence and prevalence of other diabetic complications.

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Authors and Affiliations

  1. Baker IDI Heart & Diabetes Institute, 75 Commercial Road, Melbourne, 3004, Victoria, Australia

    Merlin C. Thomas, Karin A. M. Jandeleit-Dahm & Mark E. Cooper

  2. Albert Einstein College of Medicine, Bronx, New York, New York, USA

    Michael Brownlee

  3. Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA

    Katalin Susztak

  4. Center for Renal Translational Medicine, University of California, San Diego, California, USA

    Kumar Sharma

  5. Department of Epidemiology and Preventative Medicine, Faculty of Medicine, Nursing & Health Sciences, Monash University, Melbourne, Victoria, Australia

    Sophia Zoungas

  6. Steno Diabetes Center, Gentofte, Denmark

    Peter Rossing

  7. Department of Nephrology, University of Helsinki, Helsinki, Finland

    Per-Henrik Groop

Authors
  1. Merlin C. Thomas
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  2. Michael Brownlee
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  3. Katalin Susztak
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  4. Kumar Sharma
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  5. Karin A. M. Jandeleit-Dahm
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  6. Sophia Zoungas
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  7. Peter Rossing
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  8. Per-Henrik Groop
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  9. Mark E. Cooper
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Contributions

Introduction (K.A.M.J-.D. and M.C.T.); Epidemiology (P-.H.G. and M.C.T.); Mechanisms/pathophysiology (M.B., K. Sustak and M.C.T.); Diagnosis, screening and prevention (K. Sharma and M.C.T.); Management (P.R., S.Z. and M.C.T.); Quality of Life (M.C.T.); Outlook (M.E.C. and M.C.T.); overview of Primer (M.E.C.).

Corresponding author

Correspondence to Mark E. Cooper.

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Competing interests

M.C.T. has received honoraria for educational meetings conducted on behalf of AbbVie, Boehringer Ingelheim, Eli Lilly and Company, Merck Sharpe & Dohme, Servier, Novartis, Takeda, Abbott, Allergan and AstraZeneca. M.B. declares no competing interests. K. Susztak has received research support from Boehringer Ingelheim and Biogen Idec for projects not related to this publication, and is on the advisory board of AbbVie. She has received research support from the US National Institutes of Health (NIH), the Juvenile Diabetes Research Foundation (JDRF) and the American Diabetes Association (ADA). K. Sharma has received research support from AbbVie, Boehringer Ingelheim and Stealth Peptides for projects not related to this publication, and is on the scientific advisory board of Merck and Astellas. He is founder of Clinical Metabolomics, and has received research support from the NIH, the JDRF and the ADA. K.A.M.J-.D. has received research grants from Genkyotex and Boehringer Ingelheim. S.Z. has served on the advisory board for Amgen, AstraZeneca, Bristol-Myers Squibb, Merck Sharp & Dohme, Novartis, Sanofi and Takeda Pharmaceuticals. S.Z. has received consultancy fees and honoraria from AstraZeneca, Bristol-Myers Squibb, Janssen-Cilag, Merck Sharp & Dohme and Servier Laboratories. She has received grants from the National Health and Medical Research Council and the Heart Foundation of Australia, and has undertaken institutional contract work for Bristol-Myers Squibb and the Commonwealth Department of Health. P.R. has received consultancy and/or speaking fees (to his institution) from AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Eli Lilly and Company, Novo Nordisk, Sanofi Aventis, Astellas, AbbVie and Merck Sharp & Dohme. He has received research grants from AbbVie, Novo Nordisk and Astra Zeneca. P.R. has shares in Novo Nordisk. P-.H.G. has received lecture honoraria from Boehringer Ingelheim, AstraZeneca, Genzyme, Novartis, Novo Nordisk, Merck Sharp & Dohme, Eli Lilly and Company and Medscape. M.E.C. has received honoraria and consulting fees from AbbVie, Bayer, Boehringer Ingelheim, Eli Lilly and Company, Merck Sharpe and Dohme, Servier, Takeda, Novo Nordisk and AstraZeneca, as well as research grants from Novo Nordisk and AbbVie.

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Thomas, M., Brownlee, M., Susztak, K. et al. Diabetic kidney disease. Nat Rev Dis Primers 1, 15018 (2015). https://doi.org/10.1038/nrdp.2015.18

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