[个体肾脏血流动力学对慢性血管紧张素II受体阻断的反应及其对肾素-血管紧张素系统基因多态性的影响]

[Individual renal hemodynamic response to chronic angiotensin II receptor blockade and the influence on the renin-angiotensin system gene polymorphisms].

作者信息

Dragović Tamara, Ajdinović Boris, Ilić Vesna, Magić Zvonko, Andelković Zoran, Kocev Nikola

机构信息

Klinika za endokrinologiju, Vojnomedicinska akademija, Beograd.

出版信息

Med Pregl. 2010 Sep-Oct;63(9-10):630-7. doi: 10.2298/mpns1010630d.

DOI:10.2298/mpns1010630d

PMID:21446090

Abstract

INTRODUCTION

Our study was aimed at determining whether the polymorphism of genes for different components of the renin-angiotensin-aldosterone system could influence the renal hemodynamic response to losartan treatment.

MATERIAL AND METHOD

The study included 35 patients with type I diabetes mellitus and persistent albuminuria, genotyped for the 1166 A/C polymorphism gene for the angiotensin II type 1 receptor and I/D polymorphism of the angiotensin-converting enzyme gene. The participants were divided into groups according to the combinations of A or C allele: AA, AC, CC; and according to the combinations of I or D allele: II, ID and DD genotype. The patients received losartan therapy for 12 weeks. The renal hemodynamic measurements were determined at baseline and after the examination period.

RESULTS

Losartan therapy significantly reduced the filtration fraction from the baseline by 0.018 +/- 0.024 (p = 0.012) only in the AC genotype. The glomerular filtration rate remained unchanged in all genotype groups. A significant increase in the effective renal plasma flow was obtained only in AC genotype (544 +/- 88 vs 575 +/- 90 ml/min; p = 0.02), while significant reductions in the renal vascular resistance were found in AA group (115 +/- 25 vs 95 +/- 21 mmHg x l(-1) x min(-1), p = 0.001) and in AC group (118 +/- 30 vs 101 +/- 28 mmHg x l(-1) x min(-1); p = 0.001). A significant reduction of the glomerular filtration rate by 8 +/- 10 ml/min was obtained only in the DD genotype (p = 0.016), and only the DD genotype achieved a significant reduction of the filtration fraction by 0.019 +/- 0,022 (p = 0.008). The most pronounced increase of the effective renal plasma flow was found only in the ID genotype (536 +/- 75 vs 591 +/- 63 ml/min; p = 0.01). The reduction of the renal vascular resistance was independent of ACE gene polymorphism.

CONCLUSION

Our study shows that individual renal vascular response to losartan treatment in diabetic patients with persistent albuminuria, could be influenced by genetic polymorphisms.

摘要

引言

我们的研究旨在确定肾素 - 血管紧张素 - 醛固酮系统不同组分的基因多态性是否会影响氯沙坦治疗的肾血流动力学反应。

材料与方法

该研究纳入了35例患有I型糖尿病和持续性蛋白尿的患者，对其进行血管紧张素II 1型受体1166A/C多态性基因以及血管紧张素转换酶基因I/D多态性的基因分型。参与者根据A或C等位基因的组合分为几组：AA、AC、CC；并根据I或D等位基因的组合分为：II、ID和DD基因型。患者接受氯沙坦治疗12周。在基线期和检查期后测定肾血流动力学指标。

结果

仅在AC基因型中，氯沙坦治疗使滤过分数从基线显著降低了0.018±0.024（p = 0.012）。所有基因型组的肾小球滤过率均保持不变。仅在AC基因型中有效肾血浆流量显著增加（544±88对575±90 ml/min；p = 0.02），而在AA组（115±25对95±21 mmHg· l⁻¹·min⁻¹，p = 0.001）和AC组（118±30对101±28 mmHg· l⁻¹·min⁻¹；p = 0.001）中发现肾血管阻力显著降低。仅在DD基因型中肾小球滤过率显著降低了8±10 ml/min（p = 0.016），并且只有DD基因型使滤过分数显著降低了0.019±0.022（p = 0.008）。仅在ID基因型中发现有效肾血浆流量增加最为显著（536±75对591±63 ml/min；p = 0.01）。肾血管阻力的降低与ACE基因多态性无关。