Urinary albumin excretion and the renin–angiotensin system in cardiovascular risk management

Microalbuminuria has been shown to be a strong predictor of cardiovascular morbidity and mortality in diabetic and hypertensive patients, but also in the general population. Moreover, several reports suggest that reduction of urinary albumin excretion (UAE) is associated with improvement of cardiovascular prognosis. Reduction of UAE can be achieved by lowering arterial blood pressure, but blockers of the renin-angiotensin system (RAS) with their specific renal actions have demonstrated to be able to reduce UAE more than might be expected from reduction of blood pressure alone. Consequently, angiotensin-converting enzyme inhibitors and angiotensin receptor blockers may also provide superior cardiovascular protection, especially in subjects with higher levels of albuminuria, but evidence is still scarce. The ability of both angiotensin-converting enzyme inhibitors and angiotensin receptor blockers to reduce UAE and provide cardiovascular protection suggests that the RAS may play a central role. New developments in this area include the use of aldosterone antagonists in albuminuric/proteinuric subjects, and the development of oral renin inhibitors. Combinations of the aforementioned drugs may have the ability to fully block the RAS, potentially avoiding all detrimental effects of this hormonal cascade. However, combination therapy is expected to also increase the incidence of side effects, such as hyperkalaemia and acute renal insufficiency. The current knowledge of microalbuminuria represents the proverbial tip of the iceberg, and future studies should focus on the underlying pathophysiological mechanism of urinary albumin excretion in relation to cardiovascular protection. Only then can a better understanding of the problem be achieved and the optimal pharmacological approach be ascertained.