¹Unit for Metabolic Medicine, Department of Diabetes, Endocrinology and Internal Medicine, Cardiovascular Division, King's College London School of Medicine, King's College London, London, UK

Correspondence: Dr J Karalliedde, Unit for Metabolic Medicine, Department of Diabetes, Endocrinology and Internal Medicine, Cardiovascular Division, King's College London School of Medicine, King's College London, 5th Floor Thomas Guy House, KCL Guy's Hospital Campus, London SE1 9RT, UK. E-mail: j.karalliedde@kcl.ac.uk

Received 18 August 2005; Revised 15 December 2005; Accepted 15 December 2005; Published online 2 February 2006.

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–angiotensin–aldosterone 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 -blockers.