TY - JOUR
T1 - Endothelial dysfunction as a potential contributor in diabetic nephropathy
AU - Nakagawa, Takahiko
AU - Tanabe, Katsuyuki
AU - Croker, Byron P.
AU - Johnson, Richard J.
AU - Grant, Maria B.
AU - Kosugi, Tomoki
AU - Li, Qiuhong
PY - 2011/1
Y1 - 2011/1
N2 - The mechanisms that drive the development of diabetic nephropathy remain undetermined. Only 30g-40% of patients with diabetes mellitus develop overt nephropathy, which suggests that other contributing factors besides the diabetic state are required for the progression of diabetic nephropathy. Endothelial dysfunction is associated with human diabetic nephropathy and retinopathy, and advanced diabetic glomerulopathy often exhibits thrombotic microangiopathy, including glomerular capillary microaneurysms and mesangiolysis, which are typical manifestations of endothelial dysfunction in the glomerulus. Likewise, diabetic mice with severe endothelial dysfunction owing to deficiency of endothelial nitric oxide synthase develop progressive nephropathy and retinopathy similar to the advanced lesions observed in humans with diabetes mellitus. Additionally, inhibitors of the rening-angiotensin system fail to be renoprotective in some individuals with diabetic nephropathy (due in part to aldosterone breakthrough) and in some mouse models of the disease. In this Review, we discuss the clinical and experimental evidence that supports a role for endothelial nitric oxide deficiency and subsequent endothelial dysfunction in the progression of diabetic nephropathy and retinopathy. If endothelial dysfunction is the key factor required for diabetic nephropathy, then agents that improve endothelial function or raise intraglomerular nitric oxide level could be beneficial in the treatment of diabetic nephropathy.
AB - The mechanisms that drive the development of diabetic nephropathy remain undetermined. Only 30g-40% of patients with diabetes mellitus develop overt nephropathy, which suggests that other contributing factors besides the diabetic state are required for the progression of diabetic nephropathy. Endothelial dysfunction is associated with human diabetic nephropathy and retinopathy, and advanced diabetic glomerulopathy often exhibits thrombotic microangiopathy, including glomerular capillary microaneurysms and mesangiolysis, which are typical manifestations of endothelial dysfunction in the glomerulus. Likewise, diabetic mice with severe endothelial dysfunction owing to deficiency of endothelial nitric oxide synthase develop progressive nephropathy and retinopathy similar to the advanced lesions observed in humans with diabetes mellitus. Additionally, inhibitors of the rening-angiotensin system fail to be renoprotective in some individuals with diabetic nephropathy (due in part to aldosterone breakthrough) and in some mouse models of the disease. In this Review, we discuss the clinical and experimental evidence that supports a role for endothelial nitric oxide deficiency and subsequent endothelial dysfunction in the progression of diabetic nephropathy and retinopathy. If endothelial dysfunction is the key factor required for diabetic nephropathy, then agents that improve endothelial function or raise intraglomerular nitric oxide level could be beneficial in the treatment of diabetic nephropathy.
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U2 - 10.1038/nrneph.2010.152
DO - 10.1038/nrneph.2010.152
M3 - Review article
C2 - 21045790
AN - SCOPUS:78650522881
VL - 7
SP - 36
EP - 44
JO - Nature Clinical Practice Nephrology
JF - Nature Clinical Practice Nephrology
SN - 1759-507X
IS - 1
ER -