Schrader Joachim, Lüders Stephan, Kulschewski Anke, Hammersen Frank, Züchner Christel, Venneklaas Ulla, Schrandt Günter, Schnieders Marion, Rangoonwala Badrudin, Berger Jürgen, Dominiak Peter, Zidek Walter
Department of Internal, St.-Josefs-Hospital Cloppenburg dInstitute for Hypertension and Cardiovascular Research, Cloppenburg, Germany.
J Hypertens. 2006 Mar;24(3):541-8. doi: 10.1097/01.hjh.0000209991.48928.c4.
To evaluate the impact of microalbuminuria (MAU) or tubular proteinuria (TPU) on cardiovascular and cerebrovascular events and all-cause mortality, and to assess whether a normalization of MAU and/or TPU induced by angiotensin-converting enzyme-inhibitor-based antihypertensive treatment with ramipril improves cerebrovascular prognosis in essential hypertensive patients without diabetes mellitus.
A prospective, controlled, multicenter study was performed involving 3529 hypertensive participants (average follow-up 42.5 months). Ramipril was the basic antihypertensive medication. Proteinuria analysis (albumin, alpha 1-microglobulin, SDS electrophoresis) was performed by quantitative measurement every year. Ambulatory blood pressure monitoring was performed once yearly. The main outcome determined was cardiovascular and cerebrovascular events and all-cause mortality.
In patients with TPU and/or MAU, the risk for endpoints increased significantly compared with normal (TPU, 30.0%; MAU, 54.7%; MAU + TPU, 64.0%; macroproteinuria, 74.4%). A change of protein excretion either from pathologic to normal or from normal to pathologic showed a clear trend to correlate with cerebrovascular endpoints (P = 0.056 and P = 0.055). Normal protein excretion at baseline and during follow-up indicated a significantly better prognosis than pathologic proteinuria at baseline and during follow-up. (P < 0.0001). TPU normalized in 31.9%, MAU in 30.6%, MAU + TPU in 29.3%, and macroproteinuria in 10.2% of patients. A total of 445 (25.4%) patients with normal protein excretion developed pathologic proteinuria during follow-up.
In non-diabetic hypertensive patients, MAU as well as TPU increases the incidence of cardiovascular events. Normalization of MAU, TPU or macroproteinuria during angiotensin-converting enzyme-inhibitor-based treatment correlates with a reduction of cardiovascular events. Beyond blood pressure control, normalization of MAU and TPU should be considered as a further therapeutic goal. There is a need for further studies to optimize treatment if proteinuria is unresponsive to angiotensin-converting enzyme inhibitors.
评估微量白蛋白尿（MAU）或肾小管蛋白尿（TPU）对心脑血管事件和全因死亡率的影响，并评估基于雷米普利的血管紧张素转换酶抑制剂降压治疗诱导的MAU和/或TPU正常化是否能改善无糖尿病的原发性高血压患者的脑血管预后。
进行了一项前瞻性、对照、多中心研究，纳入3529名高血压参与者（平均随访42.5个月）。雷米普利是基本的降压药物。每年通过定量测量进行蛋白尿分析（白蛋白、α1-微球蛋白、SDS电泳）。每年进行一次动态血压监测。确定的主要结局是心脑血管事件和全因死亡率。
在TPU和/或MAU患者中，与正常情况相比，终点事件风险显著增加（TPU为30.0%；MAU为54.7%；MAU+TPU为64.0%；大量蛋白尿为74.4%）。蛋白尿排泄从病理性变为正常或从正常变为病理性均显示出与脑血管终点事件明显的相关趋势（P=0.056和P=0.055）。基线和随访期间蛋白尿排泄正常表明预后明显优于基线和随访期间病理性蛋白尿（P<0.0001）。31.9%的患者TPU正常化，30.6%的患者MAU正常化，29.3%的患者MAU+TPU正常化，10.2%的患者大量蛋白尿正常化。共有445名（25.4%）蛋白尿排泄正常的患者在随访期间出现病理性蛋白尿。
在非糖尿病高血压患者中，MAU以及TPU会增加心血管事件的发生率。基于血管紧张素转换酶抑制剂的治疗期间MAU、TPU或大量蛋白尿的正常化与心血管事件的减少相关。除了控制血压外，MAU和TPU的正常化应被视为进一步的治疗目标。如果蛋白尿对血管紧张素转换酶抑制剂无反应，需要进一步研究以优化治疗。
