CIN '2007 - 4º CONGRESO DE NEFROLOGIA EN INTERNET
ACE/ACE2 in diabetic mice: implications for nephropathy
Dra María José Soler, Dr Jan Wysocki, Dr Minghao Ye, Dra Eva Rodriguez and Dr Daniel Batlle
Division of Nephrology & Hypertension, Department of Medicine. The Feinberg School of Medicine, Northwestern University. Chicago (USA). Nephrology Department Hospital del Mar Universitat Autònoma de Barcelona. Barcelona,
Abstract
Diabetic nephropathy (DN) is a microvascular complication of type 1 and type 2 diabetes, which is associated with end-stage renal disease (ESRD) and premature death from cardiovascular disease. The development of clinical nephropathy is insidious, and macroalbuminuria [urinary albumin excretion rate > 300 mg/24 hours], of the condition, is preceded by a phase of microalbuminuria (UAE 30–300 mg/24 hours), which usually lasts 5 to 10 years. As albuminuria worsens and blood pressure increases, there is a relentless decline in GFR and progression to ESRD. DN is now the most common single cause of end-stage renal disease (ESRD) in the US and Europe. Up to 40% of patients with type 2 diabetes will eventually develop diabetic nephropathy, and the number of patients progressing to ESRD has increased over the past 50 years. Although there is no cure for diabetic nephropathy, the rate of decline in renal function, and therefore progression to ESRD, can be slowed if it is detected and treated at an early stage. The renin-angiotensin system (RAS) plays an important role in the pathophysiology of many progressive renal diseases including diabetic nephropathy, and blockade of the RAS system with either angiotensin converting enzyme (ACE) or Angiotensin (ang) II receptor blockade attenuates progression of glomerular disease including DN . The recent discovery of Angiotensin converting enzyme 2, an active homologue of ACE, has expanded the knowledge of the RAS system. Whereas ACE promotes ang II formation from ang I, ACE2 promotes ang II degradation to the vasodilator peptide ang 1-7 (Figure 1). Moreover, ACE2 also catalyzes ang I to the inactive peptide ang 1-9 (Figure 1).Comentarios :