title: The renin-angiotensin-aldosterone system and its blockade in diabetic nephropathy: main focus on the role of aldosterone.
abstract: Diabetic nephropathy is the most common cause of end-stage renal disease in the western world. Despite major improvements in both prevention and treatment of diabetic nephropathy, there is a continuous need to improve identification and treatment of "non-responders". In recent years, several experimental studies have shown that aldosterone plays a role in the development and progression of diabetic nephropathy, independent of angiotensin II and blood pressure levels. Blocking the renin-angiotensin-aldosterone system with an ACE-inhibitor (ACEI) and/or ambulatory blood pressure should theoretically inhibit the secretion of aldosterone. However, an increase in aldosterone during long-term treatment with ACEIs, so-called aldosterone escape or aldosterone breakthrough, has been described. In the present thesis, our studies evaluating the incidence and clinical impact (i.e. a faster rate of decline in kidney function) of aldosterone escape in type 1 diabetic patients with diabetic nephropathy, possible mechanisms of aldosterone escape, and finally the beneficial effect of blocking aldosterone on albuminuria, blood pressure and renal autoregulation is being reviewed, together with some aspects of the existing treatment recommendations.
authors.affiliation: Department 520, Steno Diabetes Center, Gentofte, Denmark. k.jordan@dadlnet.dk
authors.forename: Katrine Jordan
authors.initials: KJ
authors.lastname: Schjoedt
mesh_terms: D000419:Albuminuria; D047228:Angiotensin II Type 1 Receptor Blockers / Q000627:therapeutic use; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D019405:Cytochrome P-450 CYP11B2 / Q000235:genetics / Q000378:metabolism; D003928:Diabetic Nephropathies / Q000188:drug therapy* / Q000473:pathology; D004232:Diuretics / Q000627:therapeutic use*; D005919:Glomerular Filtration Rate; D006801:Humans; D006929:Hyperaldosteronism / Q000473:pathology; D000451:Mineralocorticoid Receptor Antagonists / Q000627:therapeutic use*; D012084:Renin-Angiotensin System / Q000187:drug effects*; D013148:Spironolactone / Q000627:therapeutic use*
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors; D004232:Diuretics; D000451:Mineralocorticoid Receptor Antagonists; D013148:Spironolactone; D019405:Cytochrome P-450 CYP11B2