血管紧张素原基因变异与肾素-血管紧张素系统阻断对IgA肾病的肾脏保护作用

Angiotensinogen gene variation and renoprotective efficacy of renin-angiotensin system blockade in IgA nephropathy.

作者信息

Narita Ichiei, Goto Shin, Saito Noriko, Song Jin, Omori Kentaro, Kondo Daisuke, Sakatsume Minoru, Gejyo Fumitake

机构信息

Division of Clinical Nephrology and Rheumatology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.

出版信息

Kidney Int. 2003 Sep;64(3):1050-8. doi: 10.1046/j.1523-1755.2003.00187.x.

DOI:10.1046/j.1523-1755.2003.00187.x

PMID:12911556

Abstract

BACKGROUND

Blockade of the renin-angiotensin system (RAS) is well documented to be renoprotective; however, not all patients with glomerulonephritis respond well to this therapy. The interindividual variation in response to the RAS blockade may be in part genetically determined, whereas the results have been controversial.

METHODS

We investigated whether the therapeutic efficacy of angiotensin-converting enzyme (ACE) inhibitors and/or angiotensin receptor blocker on renal prognosis is modified by the angiotensinogen gene (AGT) polymorphism in immunoglobulin A nephropathy (IgAN). In total, 259 patients with histologically proven IgAN were analyzed for clinical manifestations, renal survival, and their associations with AGT A(-20)C and M235T.

RESULTS

The renal prognosis of 110 patients, who received ACE inhibitors/angiotensin receptor blocker during their clinical course, was significantly better than those without ACE inhibitors/angiotensin receptor blockers despite higher blood pressures and heavier proteinuria. The Cox proportional hazards regression model showed an increased hazard ratio (HR) for urinary protein (more than 1.0 g/day) of 3.346 (P = 0.0001), hypertension of 1.949 (P = 0.01), deteriorated renal function of 3.040 (P < 0.0001), no ACE inhibitor/angiotensin receptor blocker administration of 2.725 (P = 0.0004), and the T235 and C(-20) haplotype of 1.608 (P = 0.0322). Only in patients carrying at least one M235 and A(-20) haplotype did the administration of ACE inhibitors/angiotensin receptor blockers have no significant effect on the prognosis of renal function (Kaplan-Meier, log rank test, chi2 = 0.700; P = 0.4028), whereas it was significant in patients who had other haplotypes of AGT (chi2 = 11.805; P = 0.0006).

CONCLUSION

This study provides evidence that the M235T and A(-20)C genotype of AGT can influence the therapeutic efficacy of a RAS blockade on the renal survival in IgAN.

摘要

背景

肾素 - 血管紧张素系统（RAS）阻断具有肾脏保护作用，这已得到充分证实；然而，并非所有肾小球肾炎患者对该疗法反应良好。个体对RAS阻断反应的差异可能部分由基因决定，但其结果一直存在争议。

方法

我们研究了血管紧张素原基因（AGT）多态性是否会改变免疫球蛋白A肾病（IgAN）中血管紧张素转换酶（ACE）抑制剂和/或血管紧张素受体阻滞剂对肾脏预后的治疗效果。总共对259例经组织学证实为IgAN的患者进行了临床表现、肾脏存活率及其与AGT A（-20）C和M235T关联的分析。

结果

110例在临床过程中接受ACE抑制剂/血管紧张素受体阻滞剂治疗的患者，尽管血压更高且蛋白尿更严重，但其肾脏预后明显优于未接受ACE抑制剂/血管紧张素受体阻滞剂治疗的患者。Cox比例风险回归模型显示，尿蛋白（超过1.0 g/天）的风险比（HR）增加3.346（P = 0.0001），高血压的HR增加1.949（P = 0.01），肾功能恶化的HR增加3.040（P < 0.0001），未使用ACE抑制剂/血管紧张素受体阻滞剂的HR增加2.725（P = 0.0004），T235和C（-20）单倍型的HR增加1.608（P = 0.0322）。仅在携带至少一个M235和A（-20）单倍型的患者中，ACE抑制剂/血管紧张素受体阻滞剂的使用对肾功能预后无显著影响（Kaplan - Meier法，对数秩检验，χ2 = 0.700；P = 0.4028），而在具有其他AGT单倍型的患者中则具有显著影响（χ2 = 11.805；P = 0.0006）。