Aliskiren and Perindopril Reduce the Levels of Transforming Growth Factor-beta in Patients With Non-Diabetic Kidney Disease

作者：Lizakowski Slawomir^*; Tylicki Leszek; Renke Marcin; Rutkowski Przemyslaw; Heleniak Zbigniew; Slawinska Morawska Maja; Aleksandrowicz Wrona Ewa; Malgorzewicz Sylwia; Rutkowski Boleslaw

来源：American Journal of Hypertension, 2012, 25(6): 636-639.

DOI：10.1038/ajh.2012.14

• ACE inhibitor
• aliskiren
• blood pressure
• chronic kidney diseases
• hypertension
• procollagen III N-terminal propeptide (PIIINP)
• transforming growth factor-beta 1 (TGF-beta 1)

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-beta 1 (TGF-beta 1) 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-beta 1 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-beta 1 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.

• 出版日期2012-6