Department of Nephrology and Hypertension, University of Erlangen-Nuremberg, Germany.
Br J Clin Pharmacol. 2013 Jan;75(1):129-35. doi: 10.1111/j.1365-2125.2012.04336.x.
Intraglomerular pressure is one of the main drivers of progression of renal failure. Experimental data suggest that there are important differences between calcium channel blockers (CCBs) in their renal haemodynamic effects: manidipine reduces, whereas amlodipine increases intraglomerular pressure. The aim of this study was to investigate the effects of manidipine and amlodipine treatment on intragomerular pressure (P(glom)) in patients with mild to moderate essential hypertension.
In this randomized, double-blind, parallel group study, hypertensive patients were randomly assigned to receive manidipine 20 mg (n = 54) or amlodipine 10 mg (n = 50) for 4 weeks. Renal plasma flow (RPF) and glomerular filtration rate (GFR) were determined by constant-infusion input-clearance technique with p-aminohippurate (PAH) and inulin. P(glom) and resistances of the afferent (R(A)) and efferent (R(E)) arterioles were calculated according to the model established by Gomez.
P(glom) did not change in the manidipine group (P = 0.951), whereas a significant increase occurred in the amlodipine group (P = 0.009). There was a significant difference in the change of P(glom) by 1.2 mmHg between the manidipine and amlodipine group (P = 0.042). In both treatment arms, R(A) was reduced (manidipine P = 0.018; amlodipine P < 0.001). The reduction of R(A) was significantly more pronounced with amlodipine compared with manidipine treatment (P < 0.001). R(E) increased in both treatment arms (manidipine P = 0.012; amlodipine P = 0.002), with no difference between the treatment arms. Both CCBs significantly reduced systolic and diastolic blood pressure (BP) (both P < 0.001). However, amlodipine treatment resulted in a significantly greater decrease of BP compared with manidipine (P < 0.001).
In accordance with experimental data after antihypertensive treatment of 4 weeks, intraglomerular pressure was significantly lower with the CCB manidipine than with amlodipine, resulting and explaining their disparate effects on albuminuria.
肾小球内压是肾功能衰竭进展的主要驱动因素之一。实验数据表明,钙通道阻滞剂(CCB)在其肾脏血流动力学效应方面存在重要差异:马尼地平降低肾小球内压,而氨氯地平增加肾小球内压。本研究旨在探讨马尼地平和氨氯地平治疗对轻度至中度原发性高血压患者肾小球内压(P(glom))的影响。
在这项随机、双盲、平行组研究中,高血压患者被随机分配接受马尼地平 20mg(n=54)或氨氯地平 10mg(n=50)治疗 4 周。通过用对氨基马尿酸(PAH)和菊粉进行恒速输注清除技术来确定肾血浆流量(RPF)和肾小球滤过率(GFR)。根据 Gomez 建立的模型计算肾小球内压(P(glom))和入球小动脉(R(A))和出球小动脉(R(E))的阻力。
马尼地平组肾小球内压无变化(P=0.951),而氨氯地平组显著升高(P=0.009)。马尼地平组和氨氯地平组之间肾小球内压变化相差 1.2mmHg,差异有统计学意义(P=0.042)。在两个治疗组中,R(A)均降低(马尼地平 P=0.018;氨氯地平 P<0.001)。与马尼地平治疗相比,氨氯地平治疗时 R(A)的降低更为明显(P<0.001)。在两个治疗组中,R(E)均增加(马尼地平 P=0.012;氨氯地平 P=0.002),但两组之间无差异。两种 CCB 均显著降低收缩压和舒张压(BP)(均 P<0.001)。然而,与马尼地平相比,氨氯地平治疗导致 BP 显著下降(P<0.001)。
与 4 周降压治疗后的实验数据一致,CCB 马尼地平治疗后肾小球内压明显低于氨氯地平,这解释了它们对白蛋白尿的不同作用。