Oxidative stress as a major culprit in kidney disease in diabetes

Forbes, Josephine M., Coughlan, Melinda T. and Cooper, Mark E. (2008) Oxidative stress as a major culprit in kidney disease in diabetes. Diabetes, 57 6: 1446-1454. doi:10.2337/db08-0057

Author Forbes, Josephine M.
Coughlan, Melinda T.
Cooper, Mark E.
Title Oxidative stress as a major culprit in kidney disease in diabetes
Journal name Diabetes   Check publisher's open access policy
ISSN 0012-1797
Publication date 2008-06
Sub-type Critical review of research, literature review, critical commentary
DOI 10.2337/db08-0057
Volume 57
Issue 6
Start page 1446
End page 1454
Total pages 9
Place of publication Alexandria, VA, United States
Publisher American Diabetes Association
Language eng
Abstract It is postulated that localized tissue oxidative stress is a key component in the development of diabetic nephropathy. There remains controversy, however, as to whether this is an early link between hyperglycemia and renal disease or develops as a consequence of other primary pathogenic mechanisms. In the kidney, a number of pathways that generate reactive oxygen species (ROS) such as glycolysis, specific defects in the polyol pathway, uncoupling of nitric oxide synthase, xanthine oxidase, NAD(P)H oxidase, and advanced glycation have been identified as potentially major contributors to the pathogenesis of diabetic kidney disease. In addition, a unifying hypothesis has been proposed whereby mitochondrial production of ROS in response to chronic hyperglycemia may be the key initiator for each of these pathogenic pathways. This postulate emphasizes the importance of mitochondrial dysfunction in the progression and development of diabetes complications including nephropathy. A mystery remains, however, as to why antioxidants per se have demonstrated minimal renoprotection in humans despite positive preclinical research findings. It is likely that the utility of current study approaches, such as vitamin use, may not be the ideal antioxidant strategy in human diabetic nephropathy. There is now an increasing body of data to suggest that strategies involving a more targeted antioxidant approach, using agents that penetrate specific cellular compartments, may be the elusive additive therapy required to further optimize renoprotection in diabetes. Diabetes 57:1446-1454, 2008
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Critical review of research, literature review, critical commentary
Collection: School of Medicine Publications
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