Department of Nephrology, Transplantation and Internal Medicine, Medical University of Gdansk, Gdansk, Poland.
Am J Hypertens. 2012 Jun;25(6):636-9. doi: 10.1038/ajh.2012.14. Epub 2012 Feb 23.
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-β1 (TGF-β1) and procollagen III N-terminal propeptide (PIIINP) was evaluated in patients with nondiabetic kidney diseases.
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.
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-β1 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.
The study shows that both aliskiren and perindopril suppress TGF-β1 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.
在肾素抑制剂治疗期间，血浆前肾素和血浆肾素的升高很可能至少与血管紧张素 II 的负反馈一样，是由血压下降引起的。这可能是有害的，因为高水平的肾素和前肾素可能会刺激（前）肾素受体，从而诱导纤维增生作用。为了进一步了解这种关系，评估了阿利克仑对非糖尿病肾病患者尿转化生长因子-β1（TGF-β1）和前胶原 III N 端前肽（PIIINP）排泄的影响。
在一项交叉、随机、双盲的初步研究中，阿利克仑 300mg 和培哚普利 10mg 分别单独给药 12 周，其间间隔安慰剂期。
与安慰剂相比，阿利克仑和培哚普利治疗后血浆肾素浓度分别增加了 1131%（P<0.001）和 628%（P<0.001）。与安慰剂相比，阿利克仑和培哚普利分别使前肾素浓度增加了 100%（P<0.01）和 52.4%（P=0.53）。与安慰剂相比，两种测试疗法后的 TGF-β1 排泄量较低（55.0±7.56 与 56.21±8.56 与 85.79±14.11pg/mg 肌酐；P=0.016）；阿利克仑和培哚普利之间无差异。PIIINP 排泄在治疗之间没有差异。
该研究表明，阿利克仑和培哚普利均可抑制慢性肾脏病患者的 TGF-β1。尽管肾素和前肾素浓度显著增加，但仍观察到这种作用。需要进行涉及组织学评估的进一步研究，以阐明这些药物对肾纤维化的确切影响。
