Mori-Takeyama Urara, Minatoguchi Shinya, Murata Ichijirou, Fujiwara Hisayoshi, Ozaki Yoko, Ohno Michiya, Oda Hiroshi, Ohashi Hiroshige
Second Department of Internal Medicine, Gifu University, 1-1 Yanagido, Gifu 501-1194, Japan.
Clin Exp Nephrol. 2008 Feb;12(1):33-40. doi: 10.1007/s10157-007-0013-6. Epub 2008 Jan 5.
Proteinuria and hypertension are predictors of poor renal outcome in chronic glomerulonephritis (CGN). At the same level of blood pressure (BP) control, we evaluated which is superior, dual blockade of the rennin-angiotensin system (RAS) with both angiotensin-converting enzyme inhibitor (ACEI) and angiotensin II type 1 (AT-1) receptor blockade (ARB) or single blockade of ARB to reduce proteinuria and to preserve renal function in patients with CGN.
In this prospective, parallel, open study of 86 patients with CGN, we compared the effects on proteinuria and renal functions of 36 months with comparable blood pressure (BP) control achieved by candesartan cilexetil (candesartan, 4-12 mg/day) or benazepril hydrochrolide (benazepril, 2.5-10 mg/day) with candesartan (4 mg/day). Aiming at BP 125/75 mmHg or less, the dose of candesartan (single blockade) or benazepril (dual blockade) was increased.
Dual blockade decreased proteinuria more than single blockade with ARB (-42.3 vs. -60.5%, P < 0.01). Renal plasma flow (RPF) and glomerular filtration fraction (GFR) did not change significantly in either group. The filtration fraction (FF) decreased dual blockade more than single blockade (-1.7 vs. -19.0%, P < 0.05). Decreased FF was associated with the reduction of proteinuria (P < 0.05). Six percent of patients with dual blockade were not able to continue the study because of a dry cough.
Long-term dual blockade decreased proteinuria more than single blockade with ARB. Although ARB and ACEI have a glomerular size-selective function for proteinuria, a greater antiproteinuric effect may depend on renal hemodynamics, especially FF. Increased levels of bradykinin after ACEI can decrease FF and ameliorate proteinuria. Dry cough is a significant adverse effect of ACE inhibitor.
蛋白尿和高血压是慢性肾小球肾炎（CGN）患者肾脏预后不良的预测指标。在血压（BP）控制水平相同的情况下，我们评估了肾素 - 血管紧张素系统（RAS）双重阻断（同时使用血管紧张素转换酶抑制剂（ACEI）和血管紧张素II 1型（AT - 1）受体阻滞剂（ARB））与单一阻断ARB相比，哪种方法在降低CGN患者蛋白尿和保护肾功能方面更具优势。
在这项针对86例CGN患者的前瞻性、平行、开放性研究中，我们比较了坎地沙坦酯（坎地沙坦，4 - 12毫克/天）或盐酸贝那普利（贝那普利，2.5 - 10毫克/天）与坎地沙坦（4毫克/天）在实现可比血压（BP）控制的情况下，对蛋白尿和肾功能36个月的影响。目标血压为125/75 mmHg或更低，增加坎地沙坦（单一阻断）或贝那普利（双重阻断）的剂量。
双重阻断比单一阻断ARB降低蛋白尿的效果更显著（-42.3%对-60.5%，P < 0.01）。两组的肾血浆流量（RPF）和肾小球滤过分数（GFR）均无显著变化。双重阻断组的滤过分数（FF）下降幅度大于单一阻断组（-1.7%对-19.0%，P < 0.05）。FF降低与蛋白尿减少相关（P < 0.05）。6%接受双重阻断的患者因干咳而无法继续研究。
长期双重阻断比单一阻断ARB降低蛋白尿的效果更显著。尽管ARB和ACEI对蛋白尿具有肾小球大小选择性功能，但更大的抗蛋白尿作用可能取决于肾脏血流动力学，尤其是FF。ACEI后缓激肽水平升高可降低FF并改善蛋白尿。干咳是ACE抑制剂的显著不良反应。
