Direct renin inhibition in a rat model of chronic allograft injury.

Blockade of the renin-angiotensin system (RAS) with angiotensin-converting enzyme (ACE) inhibitors or angiotensin II (Ang II) receptor blockers (ARBs) slow the progression of various chronic kidney diseases and chronic allograft dysfunction. RAS inhibition can be achieved also by directly blocking renin upstream from ACE. However, direct renin inhibition can have additional effects since formation of renoprotective Ang II breakdown products such as angiotensin (Ang) (1-7) that are produced by ACE2 are also inhibited.Using a Fischer-to-Lewis renal transplantation model, the effect of the renin inhibitor aliskiren (10 mg/kg/day) was assessed on the development of chronic allograft dysfunction compared with vehicle treatment and Ang II receptor blockers candesartan.Aliskiren had no effect on renal function (proteinuria, creatinine clearance) or on renal morphological changes (glomerulosclerosis collagen deposition, myofibroblast accumulation and macrophage infiltration) compared with the vehicle- and candesartan-treated animals determined 24 weeks after transplantation. On the other hand, atrophy of tubular cells was significantly attenuated. Candesartan reduced both proteinuria and structural injury of the kidney. In aliskiren-treated animals reduced serum Ang II and Ang (1-7) levels were detected, whereas the level of urine angiotensinogen was unchanged.The renin inhibitor aliskiren does not slow the progression of chronic allograft dysfunction. We suggest that the lack of protection might be due to reduced formation of the protective Ang II breakdown products such as Ang (1-7) or due to unchanged intrarenal RAS activity demonstrated by urinary angiotensinogen levels.     «

Blockade of the renin-angiotensin system (RAS) with angiotensin-converting enzyme (ACE) inhibitors or angiotensin II (Ang II) receptor blockers (ARBs) slow the progression of various chronic kidney diseases and chronic allograft dysfunction. RAS inhibition can be achieved also by directly blocking renin upstream from ACE. However, direct renin inhibition can have additional effects since formation of renoprotective Ang II breakdown products such as angiotensin (Ang) (1-7) that are produced by AC...     »