Grant: Operating Grant

Diabetic nephropathy (DN) is a major cause of morbidity and mortality in both type 1 and type 2 diabetics. It is estimated that approximately 30-50% of diabetic patients in Canada and in the USA will eventually develop chronic renal failure (or end-stage renal disease). Clinical and animal experimental studies have demonstrated that intensive insulin treatment and chronic administration of angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers are effective in delaying the progression of nephropathy but are not cures. These findings suggest that hyperglycemia and renin-angiotensin system activation are major risk factors for DN. Tubulointerstitial fibrosis and tubular atrophy are closely associated with the progression of DN although the underlying mechanisms remain incompletely understood. This proposal, which concerns the molecular mechanism(s) of intrarenal RAS and albumin action on the development of cell death in kidney proximal tubular cells in diabetes, will increase our knowledge and understanding of their role(s) in the pathogenesis of DN, thereby contributing directly to improved clinical treatment.