Endothelial dysfunction as a potential contributor in diabetic nephropathy

Takahiko Nakagawa, Katsuyuki Tanabe, Byron P. Croker, Richard J. Johnson, Maria B. Grant, Tomoki Kosugi, Qiuhong Li

Research output: Contribution to journalReview article

102 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)36-44
Number of pages9
JournalNature Reviews Nephrology
Volume7
Issue number1
DOIs
StatePublished - Jan 1 2011

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Diabetic Nephropathies
Diabetic Retinopathy
Diabetes Mellitus
Nitric Oxide
Thrombotic Microangiopathies
Nitric Oxide Synthase Type III
Angiotensins
Aldosterone

ASJC Scopus subject areas

  • Nephrology

Cite this

Nakagawa, T., Tanabe, K., Croker, B. P., Johnson, R. J., Grant, M. B., Kosugi, T., & Li, Q. (2011). Endothelial dysfunction as a potential contributor in diabetic nephropathy. Nature Reviews Nephrology, 7(1), 36-44. https://doi.org/10.1038/nrneph.2010.152

Endothelial dysfunction as a potential contributor in diabetic nephropathy. / Nakagawa, Takahiko; Tanabe, Katsuyuki; Croker, Byron P.; Johnson, Richard J.; Grant, Maria B.; Kosugi, Tomoki; Li, Qiuhong.

In: Nature Reviews Nephrology, Vol. 7, No. 1, 01.01.2011, p. 36-44.

Research output: Contribution to journalReview article

Nakagawa, T, Tanabe, K, Croker, BP, Johnson, RJ, Grant, MB, Kosugi, T & Li, Q 2011, 'Endothelial dysfunction as a potential contributor in diabetic nephropathy', Nature Reviews Nephrology, vol. 7, no. 1, pp. 36-44. https://doi.org/10.1038/nrneph.2010.152
Nakagawa T, Tanabe K, Croker BP, Johnson RJ, Grant MB, Kosugi T et al. Endothelial dysfunction as a potential contributor in diabetic nephropathy. Nature Reviews Nephrology. 2011 Jan 1;7(1):36-44. https://doi.org/10.1038/nrneph.2010.152
Nakagawa, Takahiko ; Tanabe, Katsuyuki ; Croker, Byron P. ; Johnson, Richard J. ; Grant, Maria B. ; Kosugi, Tomoki ; Li, Qiuhong. / Endothelial dysfunction as a potential contributor in diabetic nephropathy. In: Nature Reviews Nephrology. 2011 ; Vol. 7, No. 1. pp. 36-44.
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