Schroten Nicolas F, Damman Kevin, Hemmelder Marc H, Voors Adriaan A, Navis Gerjan, Gaillard Carlo A J M, van Veldhuisen Dirk J, Van Gilst Wiek H, Hillege Hans L
University of Groningen, Department of Cardiology, University Medical Center Groningen, Groningen, Netherlands.
Department of Internal Medicine, Medical Center Leeuwarden, Leeuwarden, Netherlands.
Am Heart J. 2015 May;169(5):693-701.e3. doi: 10.1016/j.ahj.2014.12.016. Epub 2015 Jan 7.
We examined the effect of the renin inhibitor, aliskiren, on renal blood flow (RBF) in patients with heart failure with reduced ejection fraction (HFREF) and decreased glomerular filtration rate (GFR). Renal blood flow is the main determinant of GFR in HFREF patients. Both reduced GFR and RBF are associated with increased mortality. Aliskiren can provide additional renin-angiotensin-aldosterone system inhibition and increases RBF in healthy individuals.
Patients with left ventricular ejection fraction ≤45% and estimated GFR 30 to 75 mL/min per 1.73 m(2) on optimal medical therapy were randomized 2:1 to receive aliskiren 300 mg once daily or placebo. Renal blood flow and GFR were measured using radioactive-labeled (125)I-iothalamate and (131)I-hippuran at baseline and 26 weeks. After 41 patients were included, the trial was halted based on an interim safety analysis showing futility. Mean age was 68 ± 9 years, 82% male, GFR (49 ± 16 mL/min per 1.73 m(2)), RBF (294 ± 77 mL/min per 1.73 m(2)), and NT-proBNP 999 (435-2040) pg/mL. There was a nonsignificant change in RBF after 26 weeks in the aliskiren group compared with placebo (-7.1 ± 30 vs +14 ± 54 mL/min per 1.73 m(2); P = .16). However, GFR decreased significantly in the aliskiren group compared with placebo (-2.8 ± 6.0 vs +4.4 ± 9.6 mL/min per 1.73 m(2); P = .01) as did filtration fraction (-2.2 ± 3.3 vs +1.1 ± 3.1%; P = .01). There were no significant differences in plasma aldosterone, NT-proBNP, urinary tubular markers, or adverse events. Plasma renin activity was markedly reduced in the aliskiren group versus placebo throughout the treatment phase (P = .007).
Adding aliskiren on top of optimal HFREF medical therapy did not improve RBF and was associated with a reduction of GFR and filtration fraction.
我们研究了肾素抑制剂阿利吉仑对射血分数降低的心力衰竭（HFREF）且肾小球滤过率（GFR）降低患者肾血流量（RBF）的影响。肾血流量是HFREF患者GFR的主要决定因素。GFR和RBF降低均与死亡率增加相关。阿利吉仑可提供额外的肾素 - 血管紧张素 - 醛固酮系统抑制作用，并增加健康个体的RBF。
左心室射血分数≤45%且在最佳药物治疗下估算GFR为30至75 mL/（min·1.73 m²）的患者按2:1随机分组，分别接受每日一次300 mg阿利吉仑或安慰剂治疗。在基线和26周时使用放射性标记的（125）I - 碘肽酸盐和（131）I - 马尿酸测定肾血流量和GFR。纳入41例患者后，基于中期安全性分析显示无效而停止试验。平均年龄为68±9岁，男性占82%，GFR为（49±16 mL/（min·1.73 m²）），RBF为（294±77 mL/（min·1.73 m²）），NT - proBNP为999（435 - 2040）pg/mL。与安慰剂组相比，阿利吉仑组26周后RBF变化无统计学意义（-7.1±30 vs +14±54 mL/（min·1.73 m²）；P = 0.16）。然而，与安慰剂组相比，阿利吉仑组GFR显著降低（-2.8±6.0 vs +4.4±9.6 mL/（min·1.73 m²）；P = 0.01），滤过分数也是如此（-2.2±3.3 vs +1.1±3.1%；P = 0.01）。血浆醛固酮、NT - proBNP、肾小管标志物或不良事件方面无显著差异。在整个治疗阶段，阿利吉仑组与安慰剂组相比血浆肾素活性显著降低（P = 0.007）。
在最佳HFREF药物治疗基础上加用阿利吉仑并不能改善RBF，反而与GFR和滤过分数降低相关。
