氯沙坦在非糖尿病肾病中的抗蛋白尿作用不依赖于ACE插入/缺失多态性。

Antiproteinuric effect of losartan in non-diabetic renal disease is not dependent on ACE insertion/deletion polymorphism.

作者信息

Park Hyeong Cheon, Choi Hoon Young, Kim Beom Seok, Kang Shin Wook, Choi Kyu Hun, Ha Sung Kyu, Lee Ho Yung, Han Dae Suk

机构信息

Department of Internal Medicine, College of Medicine, Institute of Kidney Disease, Yonsei University, Seoul, Korea.

出版信息

Kidney Blood Press Res. 2006;29(4):216-24. doi: 10.1159/000095736. Epub 2006 Sep 8.

DOI:10.1159/000095736

PMID:16960460

Abstract

BACKGROUND

The antiproteinuric effect of angiotensin-converting enzyme (ACE) inhibitors appears to vary depending on the ACE insertion (I)/deletion (D) genotype in non-diabetic nephropathy. This interaction may be overcome by using an angiotensin II receptor blocker. We evaluated the short-term antiproteinuric effect of losartan according to the ACE I/D genotype in patients with non-diabetic proteinuric renal diseases.

METHODS

Ninety-nine (II/ID/DD: 36/52/11) non-diabetic patients with overt proteinuria were enrolled. The patients received losartan 50 mg daily followed by 100 mg in two treatment periods each lasting 12 weeks. Clinical parameters including proteinuria were measured at baseline and at the end of each period.

RESULTS

At baseline each genotype (II/ID/DD) had comparable mean arterial blood pressure (mean +/- SD) 103.2 +/- 11.1/102.7 +/- 10.6/104.1 +/- 15.3; proteinuria (geometric mean, 95% CI, mg/day) 1,839 (1,518-2,227)/1,998 (1,683-2,372)/1,613 (1,072-2,427), and creatinine clearance (ml/min/1.73 m(2)) 65.7 +/- 28.4/63.2 +/- 27.8/68.8 +/- 25.3, respectively. Both doses of losartan significantly lowered blood pressure and proteinuria (p < 0.05 vs. baseline), and losartan 100 mg was more effective than 50 mg in reducing proteinuria (52.5 +/- 29.0 vs. 40.5 +/- 30.8%, respectively, p = 0.001). No differences in the antiproteinuric effect of losartan was observed among the ACE I/D genotype. Losartan 100 mg demonstrated a comparable degree of mean arterial pressure (mean +/- SD, %) (II/ID/DD, 13.3 +/- 7.6/10.8 +/- 9.8/13.0 +/- 11.6, respectively, p = NS) and proteinuria reduction (mean, 95% CI) among the three genotypes (51.4% (40.3-62.5%)/53.4% (45.5-61.4%)/51.4% (40.0-63.8%), respectively, p = NS).

CONCLUSION

Our data suggest that losartan provides a similar short-term antiproteinuric response for all three genotypes of ACE I/D genotype in non-diabetic proteinuric chronic renal disease.

摘要

背景

血管紧张素转换酶（ACE）抑制剂的抗蛋白尿作用似乎因非糖尿病肾病中的ACE插入（I）/缺失（D）基因型而异。使用血管紧张素II受体阻滞剂可能会克服这种相互作用。我们根据ACE I/D基因型评估了氯沙坦对非糖尿病蛋白尿性肾病患者的短期抗蛋白尿作用。

方法

纳入99例（II/ID/DD：36/52/11）有明显蛋白尿的非糖尿病患者。患者在两个各持续12周的治疗期内每天服用50mg氯沙坦，随后服用100mg。在基线和每个治疗期末测量包括蛋白尿在内的临床参数。

结果

在基线时，每种基因型（II/ID/DD）的平均动脉血压（均值±标准差）相当（分别为103.2±11.1/102.7±10.6/104.1±15.3）；蛋白尿（几何均值，95%可信区间，mg/天）分别为1839（1518 - 2227）/1998（1683 - 2372）/1613（1072 - 2427），肌酐清除率（ml/min/1.73 m²）分别为65.7±28.4/63.2±27.8/68.8±25.3。两种剂量的氯沙坦均显著降低血压和蛋白尿（与基线相比，p < 0.05），且100mg氯沙坦在降低蛋白尿方面比50mg更有效（分别为52.5±29.0%和40.5±30.8%，p = 0.001）。在ACE I/D基因型之间未观察到氯沙坦抗蛋白尿作用的差异。100mg氯沙坦在三种基因型中的平均动脉压降低程度（均值±标准差，%）相当（II/ID/DD分别为13.3±7.6/10.8±9.8/13.0±11.6，p = 无显著性差异），蛋白尿降低程度（均值，95%可信区间）也相当（分别为51.4%（40.3 - 62.5%）/53.4%（45.5 - 61.4%）/51.4%（40.0 - 63.8%），p = 无显著性差异）。