Aliskiren reduced renal fibrosis in mice with chronic ischemic kidney injury—beyond the direct renin inhibition

Abstract

Chronic renal ischemia leads to renal fibrosis and atrophy. Activation of the renin-angiotensin-aldosterone system is one of the main mechanisms driving chronic renal ischemic injury. The aim of the present study was to define the effect of aliskiren in chronic ischemia of the kidney. Two-kidney, one-clip mice were used to study chronic renal ischemia. Aliskiren significantly lowered the blood pressure in mice with renal artery constriction (92.1±1.1 vs. 81.0±1.8 mm Hg, Po0.05). Renin expression was significantly increased in ischemic kidneys when treated with aliskiren. In addition, (Pro)renin receptor expression was decreased by aliskiren in ischemic kidneys. Aliskiren treatment significantly increased klotho expression and reduced the expression of fibrogenic cystokines, caspase-3 and Bax in ischemic kidneys. Histological examination revealed that aliskiren significantly reduced the nephrosclerosis score (4.5±1.9 vs. 7.3±0.4, Po0.05). Immunofluorescence staining also showed that aliskiren decreased the deposition of interstitial collagen I in ischemic kidneys. In conclusion, direct renin inhibition significantly reduced renal fibrosis and apoptosis following chronic renal ischemia.

Aliskiren reduces portal pressure and intrahepatic resistance in biliary cirrhotic rats

“…However, it had been shown that aliskiren increased renin expression in human plasma or mouse kidneys. 16,27 In our current study, the dose of aliskiren was small and the duration of administration was short. Therefore, different species, tissues and dosages used may explain why the liver renin expression was not altered after aliskiren was administered.…”

A Comparison of the Antihypertensive and Anti-Inflammatory Effects of Aliskiren and Ramipril Add-On Therapy in Peritoneal Dialysis Patients – A Pilot Open Label Study

“…The use of a direct renin inhibitor holds promise for more potent blockade of the RAAS system in contrast to ACEI and ARB that do not fully inhibit angiotensin and aldosterone production Moreover the putative direct action of aliskiren on prorenin/renin receptor may explain its action on inflammatory markers that are independent of angiotensin II [35]. Therefore aliskiren has a potential for more effective reduction of inflammation than angiotensin-converting enzyme inhibitors or angiotensin receptor blockers [6,8].…”

Effect of add-on direct renin inhibitor aliskiren in patients with non-diabetes related chronic kidney disease

“…In contrast, the effect of dual RAAS inhibition in non-DM patients was still unclear. Although the use of add-on DRIs has been shown to be renoprotective in various animal models of non-DM kidney disease, [12,14-17] the clinical implications are still unclear. The aim of current study, therefore, was to evaluate the potential renoprotective effect of the add-on direct renin inhibitor aliskiren in non-DM CKD patients who were already receiving ARB treatment.…”