Aliskiren attenuates oxidative stress and improves tubular status in non-diabetic patients with chronic kidney disease-Placebo controlled, randomized, cross-over study.

PURPOSE: Pharmacological inhibition of the renin-angiotensin-aldosteron system (RAAS) may have a beneficial impact on proteinuria and chronic kidney diseases (CKD) progression. Despite recent progress by means of angiotensin-converting enzyme inhibitors (ACEI) and angiotensin II receptor blockers (ARB), there is still no optimal therapy which can stop progression of the nephropathy. Recently introduced aliskiren is the first orally bioavailable direct renin inhibitor approved for the treatment of hypertension. The purpose was to evaluate the extent of oxidative stress and tubular injury after the direct renin inhibitor, aliskiren compared with placebo and perindopril in patients with non-diabetic chronic kidney disease (NDCKD). MATERIAL/METHODS: A randomized, double-blind, cross-over trial was performed in 14 patients receiving 300mg aliskiren, 10mg perindopril and placebo in random order. The end point was a change in the urinary excretion of N-acetyl-ß-D-glucosaminidase (NAG) and α1-microglobulin (α1m) and 15-F(2α)-isoprostane. RESULTS: Aliskiren reduced excretion of 15-F(2α)-isoprostane (p=0.03) and α1m (p=0.01) as compared to placebo. There were no differences between aliskiren and perindopril in this regard. NAG urine excretion did not change after aliskiren and perindopril. CONCLUSIONS: Aliskiren attenuates oxidative stress and may improve functional status of tubules in patients with NDCKD.

Aliskiren and perindopril reduce the levels of transforming growth factor-ß in patients with non-diabetic kidney disease.

BACKGROUND: It is highly likely that the rise in plasma prorenin and plasma renin during renin inhibitor treatment is induced at least as much by the fall in blood pressure (BP) as it is by the negative feedback of angiotensin II. This could potentially be harmful because high levels of renin and prorenin may stimulate the (pro)renin receptor, thus inducing profibrotic effects. To further understand this relationship, the influence of aliskiren on the urinary excretion of transforming growth factor-ß1 (TGF-ß1) and procollagen III N-terminal propeptide (PIIINP) was evaluated in patients with nondiabetic kidney diseases. METHODS: Aliskiren 300 mg and perindopril 10 mg, were each individually administered for 12 weeks separated by a placebo period in a cross-over, randomized, double-blinded pilot study. RESULTS: A 1,131% (P < 0.001) and 628% (P < 0.001) increase in plasma renin concentration was observed after the aliskiren and perindopril therapies, respectively, as compared to the placebo. Aliskiren and perindopril increased prorenin concentrations as compared to the placebo by 100% (P < 0.01) and 52.4% (P = 0.53), respectively. The TGF-ß1 excretion was lower after tested therapies compared to the placebo (55.0 ± 7.56 vs. 56.21 ± 8.56 vs. 85.79 ± 14.11 pg/mg creatinine; P = 0.016); without differences between aliskiren and perindopril. PIIINP excretion did not differ between treatments. CONCLUSIONS: The study shows that both aliskiren and perindopril suppress TGF-ß1 in patients with chronic kidney diseases. This effect was observed despite significant increases in the renin and prorenin concentrations. Further studies involving histological assessments are required to elucidate the exact impact of these agents on renal fibrosis.

Effect of aliskiren on proteinuria in non-diabetic chronic kidney disease: a double-blind, crossover, randomised, controlled trial.

AIM: To evaluate the proteinuria-lowering effect of a renin inhibitor (aliskiren), compared to placebo and to an angiotensin-converting enzyme inhibitor (perindopril), in patients with non-diabetic chronic kidney disease. METHODS: A randomised, double-blind, crossover trial was performed in 14 patients with nondiabetic chronic kidney disease with 24-h mean proteinuria of 2.01 g (95% CI, 1.36­2.66) and estimated creatinine clearance of 93±6.8 ml/min. The study consisted of five treatment periods. The patients were randomly assigned to receive aliskiren (150 mg), aliskiren (300 mg), perindopril (5 mg), perindopril (10 mg) or placebo. RESULTS: Aliskiren and perindopril reduced proteinuria. These effects were dose-dependent. Furthermore, 24-h proteinuria was reduced by 23% (mean 95% CI; 2­44) by treatment with aliskiren (150 mg), by 36% (95% CI, 17­55; P<0.001) with aliskiren (300 mg), by 7.1% (95% CI, 11­26) with perindopril (5 mg) and by 25% (95% CI, 11­39; P<0.05) with perindopril (10 mg), compared to placebo. No significant difference was found between the effects of aliskiren and perindopril. CONCLUSIONS: Aliskiren significantly reduced proteinuria. The antiproteinuric effect is probably similar to that of perindopril, for equivalent hypotensive dosages. The renin inhibitor provides a promising alternative approach for the treatment of patients with chronic proteinuric non-diabetic kidney disease.