Add-on aliskiren elicits stronger renoprotection than high-dose valsartan in type 2 diabetic KKAy mice that do not respond to low-dose valsartan

We hypothesized that aliskiren provides renoprotection in diabetic animals that did not receive sufficient renoprotection by at1-receptor antagonist treatment. type 2 diabetic kkay mice were treated with group 1: vehicle or group 2: valsartan (15 mg/kg per day) from 12 to 16 weeks of age. the mice were subsequently divided into 4 groups and treated with the following combinations of drugs for another 6 weeks: 1: group 1 kept receiving vehicle,2: group 2 continuously received 15 mg/kg per day of valsartan (val-val15),3: group 2 received 50 mg/kg per day of valsartan (val-val50),4: group 2 continuously received 15 mg/kg per day of valsartan with 25 mg/kg per day of aliskiren (val-val+ali). aliskiren exerted significant anti-albuminuric effects,whereas valsartan failed to ameliorate the albuminuria in the first four weeks. surprisingly,the increasing dosage of valsartan in the val-val50 group showed non-significant tendencies to attenuate the albuminuria compared with vehicle infusion. val-val+ali significantly suppressed the development of albuminuria and podocyte injury. val-val50 and val-val+ali showed similar suppression of angiotensin ii contents in the kidney of kkay mice. in conclusion,the anti-albuminuric effect that was observed in the type 2 diabetic mice showing no anti-albuminuric effect by valsartan can be attributed to the add-on aliskiren. © the japanese pharmacological society.