The renin-angiotensin-aldosterone system (RAAS) has a central function in the 
regulation of blood pressure. Aliskiren, the first direct renin inhibitor to be 
approved for the treatment of hypertension, blocks the RAAS at its point of 
activation. As renin inhibition acts at the top of the RAAS cascade, this 
mechanism has been proposed to offer advantages over existing modes of RAAS 
blockade. The RAAS is also considered to be a major factor in the pathogenesis 
of many renal diseases, especially diabetic nephropathy (DN), the main cause of 
end-stage renal disease. Existing therapies to block the RAAS slow the 
progression of DN, but they do not halt the disease. Therefore, more effective 
modes of interventions are needed. Studies to determine the efficacy of 
aliskiren in human renal disease are in progress. This review summarizes in vivo 
studies in which the efficacy of aliskiren was tested in experimental models of 
renal disease, and presents in vitro studies that provide insights into the 
possible mechanisms by which aliskiren confers renoprotection in animals. These 
works are discussed in the framework of the intrarenal RAAS and suggest that 
aliskiren may act by unique renoprotective mechanisms.