Evidence for renoprotection by blockade of the renin–angiotensin–aldosterone system in hypertension and diabetes

Abstract

The incidence of end-stage renal disease (ESRD) is rising worldwide, accompanied by corresponding increases in the risk of morbidity and mortality. Underlying this trend are increasing rates of hypertension and diabetes mellitus, the two most common causes of ESRD. In addition to the adverse haemodynamic effects of hypertension on the kidney, elevated blood pressure (BP) can activate components of the renin-angiotensinaldosterone system (RAAS), which, in turn, activate mediators of inflammation, oxidative stress, cell growth, and matrix accumulation. Lowering BP reduces the risk of cardiovascular events and renal damage. Accumulating evidence from clinical and laboratory studies suggests that interrupting the RAAS with therapies such as angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, and aldosterone receptor blockers can interfere with the mechanisms that promote diabetic and non-diabetic renal damage. Moreover, clinical trials of RAAS blockade have demonstrated reductions in microalbuminuria, a predictor of increased cardiorenal risk and overt nephropathy in patients with and without diabetes and/or hypertension. In this way, agents that block the RAAS should be considered the drugs of first choice as they provide enhanced renoprotection compared with other classes of antihypertensive agents such as calcium channel blockers and b-blockers.

The 2007 revised ESC/ESH Guidelines in the management of hypertension: clarifying individual patient care

“…There is still a widely held belief in the diabetes community that the renal protective effects of angiotensin receptor blocker (ARB) are unique to that class of agent. 9 That this is shared at least by angiotensin-converting enzyme inhibitor (ACEI) and to a great degree matched by most antihypertensive therapies seems less well known. 9,10 While peripheral b-blockers are clearly linked to worsening insulin resistance, this is not the case for centrally acting sympatholytics.…”

Oral adsorbent AST-120 ameliorates endothelial dysfunction independent of renal function in rats with subtotal nephrectomy

“…1 Several experimental and clinical studies have documented the renovascular protective effects of inhibitors of the reninangiotensin-aldosterone system (RAAS) and their potential usefulness for retarding the development of CKD. 2,3 However, the use of these inhibitors has not yet resulted in reduced incidence of CKD. 4 Therefore, it is important to consider another strategy to halt the development of CVD associated with CKD, in addition to the use of RAAS inhibitors.…”

Blood pressure control in the setting of diabetes mellitus: new targets, new hope for improvement?

“…14,15 For example, in the United Kingdom Prospective Diabetes Study, a systolic and diastolic BP reduction by 10 and 5 mm Hg, respectively, had greater CVD risk reduction than lowering HbA1c by a mean of 0.9%. 16 This was further substantiated by the Hypertension Optimal Treatment (HOT) study, suggesting that there should perhaps be no lower threshold beyond which BP lowering is not considered to be beneficial in the setting of DM.…”