Renal Protective Effects of Aliskiren Beyond Its Antihypertensive Property in a Mouse Model of Progressive Fibrosis

The risk of cardiovascular events and death is substantially increased by chronic renal disease.1 Renal fibrosis is the common endpoint of most chronic renal diseases, such as chronic glomerulonephritis and hypertensive and diabetic nephropathy. Tubulointerstitial fibrosis is the histological feature that correlates best with serum creatinine and progressive renal impairment;2 it is characterized by the extensive deposition of extracellular matrix, tubular atrophy, and inflammatory cell infiltrates.3,4 Glomerulosclerosis also predicts progressive renal impairment to a certain extent and is particularly important in the pathogenesis of early stages of chronic renal diseases.5 Therefore, in addition to controlling hypertension, therapy for chronic renal diseases needs to target acute and chronic inflammation as well as progressive renal fibrosis. At present, standard therapeutic regimens include the pharmacological blockade of the renin–angiotensin–aldosterone system (RAAS) by either inhibition of angiotensin-converting enzyme inhibitors (ACEi) or blockade of the angiotensin II receptor (ARB). Both therapies have been shown to delay the progression of chronic renal diseases, such as diabetic nephropathy and chronic glomerulonephritis.6–8 However, the limited efficiency of ACEis and ARBs may be caused by feedback effects on early components of the renin–angiotensin– aldosterone system and the angiotensin escape phenomenon. Therefore, despite some success with these therapies, chronic, progressive renal disease continues to present a therapeutic challenge because the prevalence of patients on chronic renal replacement therapy increases by 5–7% per year in the United States and Europe. The limitations of current therapies stimulate research in this field and the development of new treatment options. One strategy that received considerable attention is the development of the direct renin inhibitor aliskiren.9 Aliskiren is the first commercially available renin inhibitor, binding to the active site of renin. Because renin acts as the rate-limiting step in the RAAS cascade, its blockade via aliskiren may cause a more complete inhibition of the RAAS with reduced feedback escape effects compared with ACEis or ARBs.9 1Department of Nephrology and Rheumatology, University Medicine Goettingen, Goettingen, Germany. Correspondence: Oliver Gross (gross.oliver@med.uni-goettingen.de)