Effect of the Direct Renin Inhibitor Aliskiren in the Prevention of Experimental Contrast-Induced Nephropathy in the Rat

Abstract

Background: Renal vasoconstriction, activated by the renin-angiotensin system, plays a pivotal role in the pathogenesis of contrast-induced nephropathy (CIN). The purpose of this study was to evaluate the effect of aliskiren, a direct renin inhibitor, for the prophylaxis of experimental CIN in the rat. Methods: Thirty-two Wistar albino rats were divided into four groups of 8 rats each, namely the control (C), aliskiren (A), contrast media (CM) and aliskiren plus contrast media (ACM) groups. Aliskiren was given orally at a dose of 50 mg/kg/day once daily for 5 consecutive days. CIN was induced by intravenous administration of indomethacin, N-nitro-L-arginine methyl ester and high-osmolar contrast medium meglumine amidotrizoate. Renal function parameters, kidney histology and tubular expression of vascular endothelial growth factor were determined. Results: Mean serum creatinine was significantly lower (p < 0.001) and mean creatinine clearance was higher (p < 0.001) in the ACM group compared with the CM group. However, there were no differences between the ACM and CM groups in terms of tubular necrosis, proteinaceous casts, medullary congestion and vascular endothelial growth factor expression. Conclusion: Our preliminary data seem to suggest a potential role of aliskiren for the prophylaxis of CIN in an experimental rat model.

Rosuvastatin attenuates contrast-induced nephropathy through modulation of nitric oxide, inflammatory responses, oxidative stress and apoptosis in diabetic male rats

“…CIN was induced by a single intravenous injection of indomethacin (10 mg/kg), double doses of N-nitro-L-arginine methyl ester (10 mg/kg, twice at 15 and 30 min) and a single dose of meglumine amidotrizoate 60% (6 ml/kg; Urovist-Angiographin, Schering AG, Germany), according to Kedrah et al [ 21 ].…”

Aliskiren restores renal AQP2 expression during unilateral ureteral obstruction by inhibiting the inflammasome

“…Aliskiren, the only available orally effective DRI, has been demonstrated to be effective in blood pressure reduction and end-organ protection, such as cardiovascular and renal protection in preclinical and clinical experiments. In addition, aliskiren has been shown to protect kidneys from acute kidney injuries induced by either contrast (23) or ischemia-reperfusion (17,50) or by chronic kidney diseases (e.g., in diabetic nephropathy) (22,49) as well as by doxorubicin-induced nephrotoxicity (39). Aliskiren alone or in combination with other drugs has also been shown to attenuate renal fibrosis and inflammation induced by ureteral obstruction (8,42,52).…”