Hypertension and microalbuminuria: the new detrimental duo

Excretion of albumin with urine (UAE) in small amounts, i.e. microalbuminuria (MAU), also referred to as "incipient nephropathy", has long been considered a marker of early nephropathy and increased cardiovascular risk in the specific setting of diabetes mellitus. However, numerous clinical studies found an association between MAU and other cardiovascular risk factors, target organ damage and risk of cardiovascular disease in clinical contexts different from diabetes and including arterial hypertension. The present article reviews the available evidence on the clinical value of MAU in subjects with primary hypertension. In these subjects, prevalence of MAU varied from about 4% to 46% across different studies and these differences may be explained by the huge intra-individual variability in UAE, discrepancies in the technique of measurement and different definitions of MAU. A direct and continuous association between UAE and blood pressure (BP) has been found in many studies. A continuous association between UAE and left ventricular mass has also been found in most studies. In contrast, it is not yet clear whether the association between UAE and other factors including age, gender, smoking, ethnicity, insulin resistance, lipids and obesity is independent or mediated by confounders, particularly BP. From a prognostic standpoint, several longitudinal studies showed an association between MAU and the risk of future cardiovascular disease. Of particular note, in some of these studies the incidence of major cardiovascular events progressively increased with UAE starting below the conventional MAU thresholds. Thus, besides being a direct risk factor for progressive renal damage, MAU can be considered a marker, which integrates and reflects the long-term level of activity of several other detrimental factors on cardiovascular system. Antihypertensive treatment reduces UAE and such effect may be detected after just a few days of treatment. Among available antihypertensive drugs, angiotensin-converting enzyme (ACE) inhibitors and the angiotensin II receptor antagonists seem to be superior to other antihypertensive drugs in reducing UAE. The dual blockade of the renin-angiotensin system with an ACE inhibitor and an angiotensin II receptor antagonist is a new and promising approach to control UAE in hypertensive patients. Determination of MAU is recommended in the initial work-up of subjects with primary hypertension.