中国2型糖尿病患者的结节性肾小球硬化症与肾素-血管紧张素系统

Nodular glomerulosclerosis and renin angiotensin system in Chinese patients with type 2 diabetes.

作者信息

Wang Min, Zhang Xiaoxi, Song Xinnan, Zou Xia, Wu Weijie, Wang Yanchao, Lin Bingjie, Li Rong, Hu Fang, Zhao Hailu

机构信息

Institute of Basic Medical Sciences, Guilin Medical University, Guilin 541004, China; Center for Diabetic Systems Medicine, Guangxi Key Laboratory of Excellence, Guilin Medical University, Guilin 541004, China.

Center for Diabetic Systems Medicine, Guangxi Key Laboratory of Excellence, Guilin Medical University, Guilin 541004, China.

出版信息

Mol Cell Endocrinol. 2016 May 15;427:92-100. doi: 10.1016/j.mce.2016.03.008. Epub 2016 Mar 10.

DOI:10.1016/j.mce.2016.03.008

PMID:26973293

Abstract

BACKGROUND

Diabetic nephropathy (DN) is a multifactorial and polygenic disease with nodular glomerulosclerosis (NGS) pathognomonic for diabetes and hypertension. Patients with type 2 diabetes and hypertension have characteristic renin-angiotensin system (RAS) gene polymorphisms.

METHODS AND RESULTS

In this retrospective cohort study, we correlated the presence of NGS with renal function, angiotensin-converting enzyme (ACE) genotypes (DD, DI, and II), angiotensinogen (AGT) genotypes (MM, MT, and TT) and immunohistochemical staining characteristics of RAS components in 847 patients and 172 consecutive autopsy cases with type 2 diabetes. T allele of AGT was associated with macroalbuminuria (P = 0.040). Multitude regression analysis revealed ACE insertion (I)/deletion (D) polymorphism as an independent determinant for estimated glomerular filtration rate (eGFR) less than 60 mL min(-1)·1.73 m(-2) (DD carriers: odds ratio [OR] = 3.46, 95% confidence interval [CI] = 1.08-11.07; DI carriers: OR = 3.51, 95% CI = 1.63-7.56). A significant association between NGS and eGFR less than 60 mL min(-1)·1.73 m(-2) also persisted after adjusting for nonlinear relationship (P < 0.001). In NGS patients, immunoreactivity of angiotensin I converting enzyme 2 (ACE2) significantly decreased in glomeruli with mesangial nodules compared with glomeruli without the mesangial nodules.

CONCLUSIONS

These data suggest associations of ACE D allele with glomerular filtration impairment, and NGS with glomerular ACE2 down-regulation and reduced glomerular filtration in Chinese patients with type 2 diabetes.

摘要

背景

糖尿病肾病（DN）是一种多因素和多基因疾病，具有糖尿病和高血压特有的结节性肾小球硬化（NGS）。2型糖尿病和高血压患者具有特征性的肾素-血管紧张素系统（RAS）基因多态性。

方法与结果

在这项回顾性队列研究中，我们将847例患者和172例2型糖尿病连续尸检病例的NGS存在情况与肾功能、血管紧张素转换酶（ACE）基因型（DD、DI和II）、血管紧张素原（AGT）基因型（MM、MT和TT）以及RAS成分的免疫组化染色特征进行了关联分析。AGT的T等位基因与大量蛋白尿相关（P = 0.040）。多因素回归分析显示，ACE插入（I）/缺失（D）多态性是估计肾小球滤过率（eGFR）低于60 mL·min⁻¹·1.73 m⁻²的独立决定因素（DD携带者：比值比[OR] = 3.46，95%置信区间[CI] = 1.08 - 11.07；DI携带者：OR = 3.51，95% CI = 1.63 - 7.56）。在调整非线性关系后，NGS与eGFR低于60 mL·min⁻¹·1.73 m⁻²之间也存在显著关联（P < 0.001）。在NGS患者中，与无系膜结节的肾小球相比，系膜结节性肾小球中血管紧张素I转换酶2（ACE2）的免疫反应性显著降低。