血浆血管紧张素转换酶 2(ACE2)是糖尿病肾病(DKD)肾脏预后的标志物(U-CARE 研究 3)。

IF 3.7 2区 医学 Q2 ENDOCRINOLOGY & METABOLISM BMJ Open Diabetes Research & Care Pub Date : 2024-05-30 DOI:10.1136/bmjdrc-2024-004237
Asami Ueno, Yasuhiro Onishi, Koki Mise, Satoshi Yamaguchi, Ayaka Kanno, Ichiro Nojima, Chigusa Higuchi, Haruhito A Uchida, Kenichi Shikata, Satoshi Miyamoto, Atsuko Nakatsuka, Jun Eguchi, Kazuyuki Hida, Akihiro Katayama, Mayu Watanabe, Tatsuaki Nakato, Atsuhito Tone, Sanae Teshigawara, Takashi Matsuoka, Shinji Kamei, Kazutoshi Murakami, Ikki Shimizu, Katsuhito Miyashita, Shinichiro Ando, Tomokazu Nunoue, Jun Wada
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引用次数: 0

摘要

简介:ACE将血管紧张素I(Ang I)裂解为血管紧张素II(Ang II),通过Ang II 1型(AT1)受体诱导血管收缩,而ACE2将Ang II裂解为Ang(1-7),通过作用于Mas受体导致血管扩张。在糖尿病肾病(DKD)中,血浆或尿液中的 ACE2 水平是否能预测肾脏预后仍不清楚:在参加糖尿病肾病持续和快速进展尿液生物标志物研究的 777 名糖尿病患者中,对随访 9 年的 296 名患者进行了调查。血浆和尿液中 ACE2 的水平通过 ELISA 法进行测量。主要终点是估计肾小球滤过率(eGFR)比基线下降至少 30% 或开始血液透析或腹膜透析。次要终点是白蛋白-肌酐比值从基线到1年期间增加30%或减少30%:血浆 ACE2 最低三分位数的第 1 组的肾脏综合结果累积发生率明显更高(P=0.040)。在经年龄和性别调整的粗Cox回归模型中,中等和最高三等分的第2组与较好的肾脏预后相关(HR为0.56,95% CI为0.31至0.99,P=0.047)。在调整年龄、性别、收缩压、血红蛋白 A1c 和 eGFR 后,血浆 ACE2 水平与 ACR 下降 30% 有显著关系(OR 1.46,95% CI 1.044 至 2.035,p=0.027):结论:DKD患者较高的血浆ACE2基线水平对白蛋白尿的发生和进展具有保护作用,并与较少的肾脏终末点相关,这表明血浆ACE2可作为DKD的预后标志物:UMIN000011525.
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Plasma angiotensin-converting enzyme 2 (ACE2) is a marker for renal outcome of diabetic kidney disease (DKD) (U-CARE study 3).

Introduction: ACE cleaves angiotensin I (Ang I) to angiotensin II (Ang II) inducing vasoconstriction via Ang II type 1 (AT1) receptor, while ACE2 cleaves Ang II to Ang (1-7) causing vasodilatation by acting on the Mas receptor. In diabetic kidney disease (DKD), it is still unclear whether plasma or urine ACE2 levels predict renal outcomes or not.

Research design and methods: Among 777 participants with diabetes enrolled in the Urinary biomarker for Continuous And Rapid progression of diabetic nEphropathy study, the 296 patients followed up for 9 years were investigated. Plasma and urinary ACE2 levels were measured by the ELISA. The primary end point was a composite of a decrease of estimated glomerular filtration rate (eGFR) by at least 30% from baseline or initiation of hemodialysis or peritoneal dialysis. The secondary end points were a 30% increase or a 30% decrease in albumin-to-creatinine ratio from baseline to 1 year.

Results: The cumulative incidence of the renal composite outcome was significantly higher in group 1 with lowest tertile of plasma ACE2 (p=0.040). Group 2 with middle and highest tertile was associated with better renal outcomes in the crude Cox regression model adjusted by age and sex (HR 0.56, 95% CI 0.31 to 0.99, p=0.047). Plasma ACE2 levels demonstrated a significant association with 30% decrease in ACR (OR 1.46, 95% CI 1.044 to 2.035, p=0.027) after adjusting for age, sex, systolic blood pressure, hemoglobin A1c, and eGFR.

Conclusions: Higher baseline plasma ACE2 levels in DKD were protective for development and progression of albuminuria and associated with fewer renal end points, suggesting plasma ACE2 may be used as a prognosis marker of DKD.

Trial registration number: UMIN000011525.

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来源期刊
BMJ Open Diabetes Research & Care
BMJ Open Diabetes Research & Care Medicine-Endocrinology, Diabetes and Metabolism
CiteScore
9.30
自引率
2.40%
发文量
123
审稿时长
18 weeks
期刊介绍: BMJ Open Diabetes Research & Care is an open access journal committed to publishing high-quality, basic and clinical research articles regarding type 1 and type 2 diabetes, and associated complications. Only original content will be accepted, and submissions are subject to rigorous peer review to ensure the publication of high-quality — and evidence-based — original research articles.
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