Renal redox stress and remodeling in metabolic syndrome, type 2 diabetes mellitus, and diabetic nephropathy: paying homage to the podocyte.
Type 2 diabetes mellitus has reached epidemic proportions and diabetic nephropathy is the leading cause of end-stage renal disease. The metabolic syndrome constitutes a milieu conducive to tissue redox stress. This loss of redox homeostasis contributes to renal remodeling and parallels the concurrent increased vascular redox stress associated with the cardiometabolic syndrome. The multiple metabolic toxicities, redox stress and endothelial dysfunction combine to weave the complicated mosaic fabric of diabetic glomerulosclerosis and diabetic nephropathy. A better understanding may provide both the clinician and researcher tools to unravel this complicated disease process. Cellular remodeling of podocyte foot processes in the Ren-2 transgenic rat model of tissue angiotensin II overexpression (TG(mREN-2)27) and the Zucker diabetic fatty model of type 2 diabetes mellitus have been observed in preliminary studies. Importantly, angiotensin II receptor blockers have been shown to abrogate these ultrastructural changes in the foot processes of the podocyte in preliminary studies. An integrated, global risk reduction, approach in therapy addressing the multiple metabolic abnormalities combined with attempts to reach therapeutic goals at an earlier stage could have a profound effect on the development and progressive nature to end-stage renal disease and ultimately renal replacement therapy.
Hayden
Melvin R
MR
Department of Internal Medicine, Division of Endocrinology, Diabetes and Metabolism, Diabetes and Cardiovascular Disease Center, University of Missouri School of Medicine, Columbia, 65212, USA. mrh29@usmo.com
Whaley-Connell
Adam
A
Sowers
James R
JR
D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000503:physiopathology*; D003928:Diabetic Nephropathies / Q000503:physiopathology*; D004730:Endothelium, Vascular / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D007668:Kidney / Q000473:pathology / Q000503:physiopathology* / Q000648:ultrastructure; D007676:Kidney Failure, Chronic / Q000503:physiopathology*; D020780:Matrix Metalloproteinase 9 / Q000502:physiology; D024821:Metabolic Syndrome / Q000503:physiopathology*; D009569:Nitric Oxide / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000037:antagonists & inhibitors; D018384:Oxidative Stress / Q000502:physiology*; D050199:Podocytes / Q000502:physiology
D009569:Nitric Oxide; D052250:Nitric Oxide Synthase Type III; D020780:Matrix Metalloproteinase 9