Erley C M, Berger E D, Heyne N, Klass M, Krämer D, Braun N, Wolf S, Risler T
Abteilung Innere Medizin III, Medizinischen Universitätsklinik der Eberhard-Karls-Universität Tübingen.
Dtsch Med Wochenschr. 1997 Aug 1;122(31-32):953-8. doi: 10.1055/s-2008-1047714.
In patients with chronic glomerular nephropathy associated arterial hypertension and proteinuria are considered to be cardinal risk factors in the progressive deterioration of renal function. Treatment regimens which reduce proteinuria and hypertension improve prognosis. The effect of the new beta-receptor blockers compared to common ACE-Inhibitors is of special interest.
The studied cohort consisted of 11 patients with CGN, hypertension and proteinuria > 400 mg/24 h. Four drugs were given for 4 weeks, doubly blinded and randomized according to a "Latin-square design": Celiprolol (beta-1-antagonist, beta-2-agonist, 200 mg/d), Atenolol (selective beta-1-antagonist, 50 mg/d), Ramipril (ACE-inhibitor, 2.5 mg/d) and placebo. There was a two-week wash-out phase between each of the four treatment phases. At the end of each treatment phase glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were measured by inulin and para-amino-hippuric acid (PAH) clearance. Proteinuria was determined in the course of a three-day collection period at the end of each treatment phase. During this period blood pressures were measured with a continuous 24-hour blood pressure monitor.
Mean arterial blood pressure (MAP) was significantly reduced, compared with placebo, by all three antihypertensives (108 +/- 9 mm Hg with placebo, 98 +/- 12 mg Hg with atenolol, 101 +/- 11 mm Hg with celiprolol and 98 +/- 8 mm Hg with ramipril; P < 0.01). Celiprolol produced a significant rise In ERPF (322 +/- 109 ml/min with placebo, 391 +/- 110 ml/min with celiprolol: P < 0.05). GFR was slightly, but not significantly, reduced by celiprolol and atenolol. Filtration fraction remained unchanged with atenolol and celiprolol, while it was slightly, but not significantly, reduced with ramipril. Compared with the placebo, all three drugs significantly reduced proteinuria (P < 0.05): 1.8 +/- 1.3 g/24 h with placebo, 1.2 +/- 1.2 g/24 h with atenolol, 1.2 +/- 1.1 g/24 h with celiprolol and 1.4 +/- 1.4 g/24 h with ramipril.
These data indicate that, in addition to ACE inhibitors, the new generation of beta-receptor blockers in particular, because of their vasodilator action, favourably influence proteinuria and renal blood flow in patients with CGN and arterial hypertension.
在慢性肾小球肾炎患者中，动脉高血压和蛋白尿被认为是肾功能进行性恶化的主要危险因素。降低蛋白尿和高血压的治疗方案可改善预后。新型β受体阻滞剂与常用的血管紧张素转换酶抑制剂（ACE抑制剂）相比的效果尤其令人关注。
研究队列包括11例慢性肾小球肾炎、高血压且蛋白尿>400mg/24小时的患者。根据“拉丁方设计”，双盲随机给予四种药物治疗4周：塞利洛尔（β1拮抗剂、β2激动剂，200mg/天）、阿替洛尔（选择性β1拮抗剂，50mg/天）、雷米普利（ACE抑制剂，2.5mg/天）和安慰剂。四个治疗阶段之间均有两周的洗脱期。在每个治疗阶段结束时，通过菊粉和对氨基马尿酸（PAH）清除率测定肾小球滤过率（GFR）和有效肾血浆流量（ERPF）。在每个治疗阶段结束时，通过连续三天收集尿液来测定蛋白尿。在此期间，使用连续24小时血压监测仪测量血压。
与安慰剂相比，所有三种抗高血压药物均显著降低了平均动脉血压（MAP）（安慰剂组为108±9mmHg，阿替洛尔组为98±12mmHg，塞利洛尔组为101±11mmHg，雷米普利组为98±8mmHg；P<0.01）。塞利洛尔使ERPF显著升高（安慰剂组为322±109ml/分钟，塞利洛尔组为391±110ml/分钟：P<0.05）。塞利洛尔和阿替洛尔使GFR略有降低，但不显著。阿替洛尔和塞利洛尔使滤过分数保持不变，而雷米普利使其略有降低，但不显著。与安慰剂相比，所有三种药物均显著降低了蛋白尿（P<0.05）：安慰剂组为1.8±1.3g/24小时，阿替洛尔组为1.2±1.2g/24小时，塞利洛尔组为1.2±1.1g/24小时，雷米普利组为1.4±1.4g/24小时。
这些数据表明，除ACE抑制剂外，新一代β受体阻滞剂，特别是因其血管舒张作用，对慢性肾小球肾炎和动脉高血压患者的蛋白尿和肾血流量有有利影响。
