Advances in the treatment of diabetic renal disease: focus on losartan.
Diabetic nephropathy is the leading cause of end stage renal disease (ESRD), and given that treating this condition is a considerable economic burden, the prevention of ESRD is a major public health goal. The renin-angiotensin system (RAS) is aberrantly activated in patients with diabetes. Angiotensin II (AII), a downstream effector of the RAS, has haemodynamic and non-haemodynamic effects that contribute to the development and progression of nephropathy. For patients with type 2 diabetes mellitus (T2DM) and hypertension, an AII receptor blocker (AIIRB) is recommended as the first drug that should be used. This review will focus on the rationale for the use of losartan as a treatment for nephropathy associated with T2DM. In animal models of diabetes, losartan reduced proteinuria and conferred renal protection. In RENAAL (Reduction in Endpoints in Non-Insulin-Dependent Diabetes Mellitus with the Angiotensin II Antagonist Losartan), the first major randomised trial that investigated the benefit of losartan in patients with T2DM and nephropathy, losartan significantly reduced the risk of a doubling of serum creatinine and progression to ESRD, significantly lowered the levels of proteinuria and slowed the rate of decline in glomerular filtration rate. This review also discusses other clinical trials of losartan and other AIIRBs in T2DM, and considers alternative mechanisms by which losartan may be exerting its effects. The collective experience in treatment trials highlighted in this review indicate that losartan and other AIIRBs can reduce blood pressure and the progression of proteinuria in diabetic renal disease. However, losartan is thus far the only AIIRB that has been shown to reduce significantly the risk of ESRD and cardiovascular events in patients with T2DM. Its use in hypertensive patients with T2DM and nephropathy may play an important role in reducing the burden of ERSD.
Rayner
Brian
B
Division of Nephrology, Groote Schuur Hospital and University of Cape Town, Cape Town, South Africa. rayner@curie.uct.ac.za
D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology / Q000627:therapeutic use*; D002318:Cardiovascular Diseases / Q000517:prevention & control; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy; D003928:Diabetic Nephropathies / Q000188:drug therapy* / Q000517:prevention & control; D006801:Humans; D006973:Hypertension / Q000188:drug therapy; D007676:Kidney Failure, Chronic / Q000517:prevention & control; D019808:Losartan / Q000494:pharmacology / Q000627:therapeutic use*; D023421:Models, Animal; D011507:Proteinuria / Q000517:prevention & control; D012084:Renin-Angiotensin System / Q000187:drug effects; D012306:Risk
D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D019808:Losartan