Renin inhibitors: optimal strategy for renal protection

Diabetic nephropathy and hypertension are the major causes of chronic kidney disease. The renin system plays a key role in the control of blood pressure (BP), as well as in the regulation of renal and adrenal function. Chronic activation of the renin system can lead to organ damage, particularly renal damage; increasing evidence indicates that suppression of the renin system can provide renal protection. Despite the use of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs), the renin system is not completely suppressed. The direct renin inhibitors (DRIs) provide suppression of the entire renin system at the rate-limiting step. Studies in humans with early DRIs indicated potential renoprotective effects, but these agents failed in clinical development due to poor oral bioavailability. Aliskiren is a new orally active DRI with proven BP-lowering effects. Animal studies indicate that aliskiren may provide renal protection, and data from human studies are anticipated.