Proteinuria reduction: mandatory consideration or option when selecting an antihypertensive agent?

Proteinuria is a known risk factor for both cardiovascular disease and progression of established kidney disease. Observational studies and intervention trials have established that even low levels of albuminuria (microalbuminuria) are associated with increased risk for cardiovascular morbidity and mortality in general, and especially in high-risk populations such as those with diabetes mellitus. People with hypertension are at increased risk for proteinuria and arguably should be treated with regimens that not only lower blood pressure but also reduce proteinuria. Clinical trials indicate that lowering proteinuria in those with chronic kidney disease is associated with reduced risk for progression to end-stage kidney disease and cardiovascular outcomes. Many of these trials employ antihypertensive agents that block the renin-angiotensin-aldosterone system (RAAS), and indicate that these drugs are, in general, more effective than other antihypertensive regimens for reducing proteinuria. In addition, several small studies suggest that nondihydropyridine calcium channel blockers are comparable with angiotensin-converting enzyme inhibitors and more effective than dihydropyridine calcium channel blockers for reducing proteinuria in type 2 diabetics with advanced kidney disease. Based on the combined evidence from epidemiologic and intervention studies, it seems prudent to make proteinuria reduction a mandatory consideration in the selection of antihypertensive regimens.