Albuminuria: a target for treatment of type 2 diabetic nephropathy

Both renal and cardiovascular morbidity and mortality is increased markedly in patients with type 2 diabetes. Besides the classic risk factors and markers such as glucose, blood pressure, blood lipid profile, and lifestyle (smoking, overweight), novel risk markers are identified, among them urine albumin excretion. Levels of urinary albumin excretion greater than normal are observed frequently in patients with type 2 diabetes. Moderately increased levels of albuminuria, so-called microalbuminuria, are predictive both for progressive renal function loss to diabetic nephropathy, and for cardiovascular morbidity and mortality: the higher the albuminuria level, the more chance of renal and cardiovascular complications. More advanced levels of albuminuria (overt albuminuria) are observed in patients in the diabetic nephropathy state. In this condition, renal and cardiovascular risk are extremely high, and again one may observe that the level of albumin excretion is predictive of renal and cardiovascular outcome. Several drug strategies decrease the level of urinary albumin excretion in type 2 diabetic patients. Data on using drugs that intervene in the renin-angiotensin-aldosterone-system (RAAS) are the most extensive and conclusive. RAAS intervention is a very effective strategy to decrease the amount of albumin in the urine, independent from the blood pressure decreasing characteristics of the treatment. RAAS intervention is associated with long-term renal and cardiovascular protection. Importantly, the degree of short-term albuminuria decrease is associated with the degree of renal and cardiovascular protection: the more albuminuria reduction, the more protection. The protective predictive power of the albuminuria effect of RAAS intervention is not related to (or dissociated from) the blood pressure decreasing effect of these drugs. The protective effect of RAAS intervention is present at normoalbuminuric, microalbuminuric, and overt albuminuria levels. This makes albuminuria a target for therapy in type 2 diabetes. New drug strategies that decrease or prevent albuminuria without affecting other risk factors currently are being tested, and not only will add to underscoring the need to treat albuminuria as a separate target, but also will assist in reducing the enormous residual risk burden of individual diabetic patients.