Blockade of the renin–angiotensin–aldosterone system: a key therapeutic strategy to reduce renal and cardiovascular events in patients with diabetes

Abstract

Diabetes (particularly type 2 diabetes) represents a global health problem of epidemic proportions. Individuals with diabetes are not only more likely to develop hypertension, dyslipidemia, and obesity, but are also at a significantly higher risk for coronary heart disease, peripheral vascular disease, and stroke. Angiotensin II plays a key pathophysiological role in the progression of diabetic renal disease, and blockade of the renin-angiotensin system with angiotensin-converting enzyme inhibitors (ACEi) or angiotensin II antagonists has therefore become an important therapeutic strategy to reduce renal and cardiovascular events in patients with diabetes. Several studies have demonstrated the effects of angiotensin II antagonists on the reduction of albuminuria and the progression of renal disease from microalbuminuria to macroalbuminuria. More importantly, several endpoint trials have shown that the antiproteinuric effects of losartan and irbesartan translate into cardiovascular and renoprotective benefits beyond blood pressure lowering, thereby delaying the need for dialysis or kidney transplantation by several years. These and other studies indicate that angiotensin II antagonists not only improve survival and quality of life of patients with diabetic nephropathy, but also have the potential to reduce the substantial healthcare burden associated with managing these patients. ACEi also appear to exert similar beneficial effects in diabetic patients, but whether clinically significant differences in renoprotection or mortality exist between angiotensin II antagonists and ACEi in patients with type 2 diabetes remains to be fully investigated in appropriate head-to-head studies.

Renal Allograft Fibrosis: Biology and Therapeutic Targets

“…Renin-angiotensin system and endothelin system ACE inhibitors (ACE-I) and angiotensin-II receptor blockers (ARB) are the first-line therapy in patients with chronic kidney disease (223). Activation of the intrarenal/intragraft renin-angiotensin system was found as early as 2 months after transplantation (224).…”

Early referral strategies for management of people with markers of renal disease: a systematic review of the evidence of clinical effectiveness, cost-effectiveness and economic analysis

“…Our findings are also consistent with the substantial body of evidence that shows early treatment of diabetic nephropathies with ACE Is or ARBs to be highly cost-effective, owing to their preventive effect on progression to ESRD. 215,216 Strengths and weakness of the study…”

Change in Albuminuria Is Predictive of Cardiovascular Outcome in Normotensive Patients With Type 2 Diabetes and Microalbuminuria

“…Moreover, they reduce albuminuria up to 40%, significantly more than other classes of antihypertensive drugs (4). Since albuminuria is strongly associated with cardiovascular outcome, changes in albuminuria during treatment might reflect changes in cardiovascular disease risk (13,14). A few studies recently showed that reduction of albuminuria in hypertensive diabetic patients reduces the risk of subsequent cardiovascular events (10 -12,15).…”