Galectin-3 and kidney function in type 2 diabetes treated with dapagliflozin: Analysis from DECLARE-TIMI 58.

IF 3.7 2区医学 Q2 CARDIAC & CARDIOVASCULAR SYSTEMS

ESC Heart Failure Pub Date : 2025-09-15 DOI:10.1002/ehf2.15415

Paul M Haller, Stephen D Wiviott, David D Berg, Petr Jarolim, Erica L Goodrich, Deepak L Bhatt, Ingrid Gause-Nilsson, Lawrence A Leiter, Darren K McGuire, John P H Wilding, Itamar Raz, Marc S Sabatine, David A Morrow

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引用次数: 0

Abstract

Background: Galectin-3 (Gal-3) is a circulating biomarker of fibrosis, with higher levels being associated with an increased risk of progression of heart failure and kidney disease. Patients with type 2 diabetes mellitus (T2DM) are at increased risk of both.

Methods: DECLARE-TIMI 58 was a randomized, placebo-controlled trial of dapagliflozin in patients with T2DM with or at high risk for atherosclerotic cardiovascular disease and creatinine clearance ≥60 mL/min. In a nested biomarker substudy, Gal-3 was measured at baseline and in adjusted analyses associated with the prespecified kidney-specific composite endpoint [Kidney-EP; sustained ≥40% decrease in estimated glomerular filtration rate (eGFR) to <60 mL/min, new end-stage kidney disease or adjudicated kidney-related death].

Results: Among 14 530 pts, median Gal-3 was 14.9 ng/mL [interquartile range (IQR), 11.9, 18.4]. Gal-3 was weakly associated with urine albumin creatinine ratio (r = 0.098, P < 0.0001) and eGFR (r = -0.27, P < 0.001) at baseline and independently associated with the Kidney-EP:adj hazard ratio (HR) 1.15 [95% confidence interval (CI) 1.03, 1.28] per 1-SD log (Gal-3), P = 0.013. Dapagliflozin significantly reduced the relative risk of the Kidney-EP across quartiles of baseline Gal-3 [overall HR 0.45 (95% CI 0.23, 0.85), P < 0.0001; P interaction = 0.87]. A greater risk difference was observed with dapagliflozin in patients with higher Gal-3, in whom a higher absolute risk at baseline was observed [absolute risk reduction (ARR) Q4 1.9 (95% CI 0.6, 3.2) vs. Q1 0.6% (-0.1, 1.3), ARR P trend 0.048].

Conclusions: Plasma Gal-3 is independently associated with the progression of kidney dysfunction in patients with T2DM and normal kidney function. There was a gradient of greater absolute benefit for reducing kidney disease progression in patients treated with dapagliflozin and with higher Gal-3 concentrations at baseline, in whom a higher absolute risk was observed.

Registration: clinicaltrials.gov (NCT01730534).

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达格列净治疗2型糖尿病的半乳糖凝集素-3和肾功能：DECLARE-TIMI的分析

背景：半乳糖凝集素-3 （Gal-3）是一种纤维化的循环生物标志物，其水平升高与心力衰竭和肾脏疾病进展的风险增加有关。2型糖尿病（T2DM）患者在这两方面的风险都增加。方法：DECLARE-TIMI 58是一项随机、安慰剂对照试验，在伴有或有动脉粥样硬化性心血管疾病高风险的T2DM患者中应用达格列净，且肌酐清除率≥60 mL/min。在一项嵌套生物标志物亚研究中，Gal-3在基线和与预先指定的肾特异性复合终点相关的调整分析中被测量[Kidney-EP；结果：在14530名患者中，Gal-3的中位数为14.9 ng/mL[四分位数间距（IQR）， 11.9, 18.4]。结论：在肾功能正常的T2DM患者中，血浆Gal-3与肾功能的进展独立相关。在接受达格列净治疗的患者和基线时Gal-3浓度较高的患者中，观察到更高的绝对风险，在减少肾脏疾病进展方面有更大的绝对获益梯度。注册：clinicaltrials.gov （NCT01730534）。

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来源期刊

ESC Heart Failure Medicine-Cardiology and Cardiovascular Medicine

CiteScore

7.00

自引率

7.90%

发文量

461

审稿时长

12 weeks

期刊介绍： ESC Heart Failure is the open access journal of the Heart Failure Association of the European Society of Cardiology dedicated to the advancement of knowledge in the field of heart failure. The journal aims to improve the understanding, prevention, investigation and treatment of heart failure. Molecular and cellular biology, pathology, physiology, electrophysiology, pharmacology, as well as the clinical, social and population sciences all form part of the discipline that is heart failure. Accordingly, submission of manuscripts on basic, translational, clinical and population sciences is invited. Original contributions on nursing, care of the elderly, primary care, health economics and other specialist fields related to heart failure are also welcome, as are case reports that highlight interesting aspects of heart failure care and treatment.