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服用呋塞米或托塞米的心力衰竭患者的蛋白质组学差异。

Proteomic differences among patients with heart failure taking furosemide or torsemide.

机构信息

Department of Cardiology, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Manhasset, New York, USA.

Inova Heart & Vascular Institute, Inova Fairfax Hospital, Falls Church, Virginia, USA.

出版信息

Clin Cardiol. 2022 Mar;45(3):265-272. doi: 10.1002/clc.23733. Epub 2022 Jan 11.

Abstract

BACKGROUND

Loop diuretics are commonly used for patients with heart failure (HF) but it remains unknown if one loop diuretic is clinically superior.

HYPOTHESIS

Biomarkers and proteomics provide insight to how different loop diuretics may differentially affect outcomes.

METHODS

Blood and urine were collected from outpatients with HF who were taking torsemide or furosemide for >30 days. Differences were assessed in cardiac, renal, and inflammatory biomarkers and soluble protein panels using the Olink Cardiovascular III and inflammation panels.

RESULTS

Of 78 subjects, 55 (71%) were treated with furosemide and 23 (29%) with torsemide, and 25 provided a urine sample (15 treated with furosemide, 10 with torsemide). Patients taking torsemide were older (68 vs 64 years) with a lower mean eGFR (46 vs 54 ml/min/1.73 m ), a higher proportion were women (39% vs 24%) and Black (43% vs 27%). In plasma, levels of hs-cTnT, NT-proBNP, and hsCRP were not significantly different between groups. In urine, there were significant differences in urinary albumin, β-2M, and NGAL, with higher levels in the torsemide-treated patients. Of 184 proteins testing in Olink panels, in plasma, 156 (85%) were higher in patients taking torsemide but none were significantly different after correcting for false discovery.

CONCLUSIONS

We show differences in urinary biomarkers but few differences in plasma biomarkers among HF patients on different loop diuretics. Olink technology can detect differences in plasma protein levels from multiple biologic domains. These findings raise the importance of defining differences in mechanisms of action of each diuretic in an appropriately powered study.

摘要

背景

袢利尿剂常用于心力衰竭(HF)患者,但目前尚不清楚一种袢利尿剂在临床上是否更具优势。

假设

生物标志物和蛋白质组学提供了不同袢利尿剂可能如何影响结果的见解。

方法

收集服用托塞米或呋塞米超过 30 天的 HF 门诊患者的血液和尿液。使用 Olink 心血管 III 和炎症面板评估心脏、肾脏和炎症生物标志物以及可溶性蛋白谱的差异。

结果

在 78 名受试者中,55 名(71%)接受呋塞米治疗,23 名(29%)接受托塞米治疗,25 名提供了尿液样本(15 名接受呋塞米治疗,10 名接受托塞米治疗)。服用托塞米的患者年龄较大(68 岁 vs 64 岁),平均 eGFR 较低(46 vs 54 ml/min/1.73 m ),女性比例较高(39% vs 24%),黑人比例较高(43% vs 27%)。在血浆中,hs-cTnT、NT-proBNP 和 hsCRP 水平在两组之间无显著差异。在尿液中,尿白蛋白、β-2M 和 NGAL 的水平存在显著差异,托塞米治疗组的水平较高。在 Olink 面板中检测的 184 种蛋白质中,有 156 种(85%)在服用托塞米的患者中较高,但在纠正假发现后,没有一种有显著差异。

结论

我们在不同袢利尿剂治疗的 HF 患者中显示出尿液生物标志物的差异,但血浆生物标志物差异较小。Olink 技术可以检测来自多个生物学领域的血浆蛋白水平差异。这些发现强调了在适当的研究中定义每种利尿剂作用机制差异的重要性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/05f1/8922525/1c7aeeb6c815/CLC-45-265-g002.jpg

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