High intraglomerular pressure is associated with renal hyperf iltration, leading to the initiation and progression of kidney disease in experimental models of diabetes mellitus (DM). In humans, hyperf iltration is obs...High intraglomerular pressure is associated with renal hyperf iltration, leading to the initiation and progression of kidney disease in experimental models of diabetes mellitus (DM). In humans, hyperf iltration is observed in patients with type 1 and type 2 DM, and is also seen in patients with pre-diabetic conditions, such as the metabolic syndrome. From a mechanistic perspective, both vascular and tubular factors likely contribute to the pathogenesis of hyperf iltration. Until now, human studies have primarily focused on the use of medications that inhibit the renin angiotensin system to reduce efferent vasoconstriction and thereby improve hyperfiltration. More recent advances in the development of investigational adenosine antagonists and inhibitors of sodium glucose cotransport may help to elucidate tubular factors that contribute to afferent vasodilatation. In this review, we summarize available data from experimental and human studies of type 1 and type 2 DM and obesity to provide an overview of factors that contribute to the hyperf iltration state. We have focused on the renin angiotensin system, cyclooxygenase-2 system, nitric oxide, protein kinase C and endothelin as vascular determinants of hyperfiltration. We also dis-cuss relevant tubular factors, since experimental models have suggested that inhibition of sodium-glucose cotransport may be renoprotective.展开更多
基金Supported by A Canadian Diabetes Association-KRESCENT Program Joint New Investigator Awardthe CIHR and the Heart and Stroke Foundation of Canada to Cherney ZID
文摘High intraglomerular pressure is associated with renal hyperf iltration, leading to the initiation and progression of kidney disease in experimental models of diabetes mellitus (DM). In humans, hyperf iltration is observed in patients with type 1 and type 2 DM, and is also seen in patients with pre-diabetic conditions, such as the metabolic syndrome. From a mechanistic perspective, both vascular and tubular factors likely contribute to the pathogenesis of hyperf iltration. Until now, human studies have primarily focused on the use of medications that inhibit the renin angiotensin system to reduce efferent vasoconstriction and thereby improve hyperfiltration. More recent advances in the development of investigational adenosine antagonists and inhibitors of sodium glucose cotransport may help to elucidate tubular factors that contribute to afferent vasodilatation. In this review, we summarize available data from experimental and human studies of type 1 and type 2 DM and obesity to provide an overview of factors that contribute to the hyperf iltration state. We have focused on the renin angiotensin system, cyclooxygenase-2 system, nitric oxide, protein kinase C and endothelin as vascular determinants of hyperfiltration. We also dis-cuss relevant tubular factors, since experimental models have suggested that inhibition of sodium-glucose cotransport may be renoprotective.
