Dapagliflozin Reduces Ambulatory Arterial Stiffness Index in CKD Patients with and Without Diabetes Independently of Blood Pressure Control: Results from the GLUcose Transport and Renal PROtection in Chronic Kidney Disease (GLUTREPRO) Trial.

IF 2.9 Q2 PERIPHERAL VASCULAR DISEASE

High Blood Pressure & Cardiovascular Prevention Pub Date : 2026-01-01 Epub Date: 2025-12-09 DOI:10.1007/s40292-025-00764-3

Elisa Russo, Francesca Cappadona, Lucia Macciò, Julie Di Vincenzo, Michela Piaggio, Daniela Verzola, Giuseppe Chirco, Giacomo Garibotto, Pasquale Esposito, Francesca Viazzi

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引用次数: 0

Abstract

Introduction: Sodium-glucose cotransporter 2 inhibitors (SGLT2i) confer cardiovascular and renal protection, but their impact on blood pressure (BP) and vascular stiffness in chronic kidney disease (CKD) is not fully defined.

Aim: To investigate the effect of dapagliflozin on 24h-BP behavior and ambulatory arterial stiffness index (AASI) as a predefined secondary outcome of the GLUTREPRO trial.

Methods: In this randomized trial, 32 patients with albuminuric CKD received dapagliflozin 10 mg/day or placebo on top of optimized standard therapy. Laboratory tests, ambulatory blood pressure monitoring (ABPM), and bioimpedance were performed at baseline and during follow-up. The study comprised a 6-month randomized phase and a 12-month open-label phase, analyzed with mixed-effects models.

Results: Baseline characteristics were balanced (mean age 58 ± 14 years, 37% diabetes, eGFR 50.6 ± 17.3 ml/min/1.73 m², UACR 582 ± 893 mg/g). Dapagliflozin induced an early eGFR dip (-3 to -6 ml/min/1.73m²) followed by stabilization. Overall, UACR did not change significantly, but patients with baseline microalbuminuria showed lower UACR after six months versus placebo. ABPM revealed no significant differences in BP or dipping status. Conversely, dapagliflozin significantly reduced AASI at 6 months (0.50 vs. 0.62; p = 0.04), with a trend toward sustained improvement thereafter. Multivariable regression identified dapagliflozin as an independent predictor of lower AASI (β = - 0.067; 95% CI -0.130 to -0.002; p = 0.043), independent of diabetes, 24-h Systolic BP, heart rate, kidney function, fractional sodium excretion, and TyG index.

Conclusion: In patients with albuminuric CKD, dapagliflozin lowered AASI independently of BP control and sodium handling, suggesting favorable vascular remodeling in both diabetic and non-diabetic patients.

Trial registration: The study was registered in the EU Clinical Trials Register (EudraCT: 2020-004835-26) and online at the https://www.

Clinicaltrials: gov (Unique identifier: NCT05998837, 13th April 2021).

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达格列净在独立于血压控制的情况下降低伴有和不伴有糖尿病的CKD患者的动态动脉僵硬指数：来自慢性肾脏疾病中葡萄糖转运和肾脏保护（GLUTREPRO）试验的结果

钠-葡萄糖共转运蛋白2抑制剂（SGLT2i）具有心血管和肾脏保护作用，但其对慢性肾脏疾病（CKD）患者血压（BP）和血管硬度的影响尚不完全明确。目的：研究达格列净对24h-BP行为和动态动脉僵硬指数（AASI）的影响，这是GLUTREPRO试验的预定次要终点。方法：在这项随机试验中，32例蛋白尿CKD患者在优化标准治疗的基础上接受达格列净10mg /天或安慰剂治疗。在基线和随访期间进行实验室检查、动态血压监测（ABPM）和生物阻抗。该研究包括6个月的随机阶段和12个月的开放标签阶段，采用混合效应模型进行分析。结果：基线特征平衡（平均年龄58±14岁，37%糖尿病，eGFR 50.6±17.3 ml/min/1.73 m2, UACR 582±893 mg/g）。达格列净诱导早期eGFR下降（-3至-6 ml/min/1.73m2），随后稳定。总体而言，UACR没有显著变化，但基线微量白蛋白尿患者在6个月后的UACR低于安慰剂。ABPM显示血压和浸出状态无显著差异。相反，达格列净在6个月时显著降低AASI (0.50 vs. 0.62; p = 0.04)，此后有持续改善的趋势。多变量回归鉴定达格列净是AASI较低的独立预测因子（β = - 0.067; 95% CI -0.130至-0.002;p = 0.043），独立于糖尿病、24小时收缩压、心率、肾功能、钠排泄分数和TyG指数。结论：在蛋白尿CKD患者中，达格列净降低AASI独立于血压控制和钠处理，表明糖尿病和非糖尿病患者的血管重构有利。试验注册：该研究已在欧盟临床试验注册中心（EudraCT: 2020-004835-26）和https://www.Clinicaltrials: gov在线注册（唯一标识符：NCT05998837, 2021年4月13日）。

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来源期刊

High Blood Pressure & Cardiovascular Prevention PERIPHERAL VASCULAR DISEASE-

CiteScore

5.70

自引率

3.30%

发文量

期刊介绍： High Blood Pressure & Cardiovascular Prevention promotes knowledge, update and discussion in the field of hypertension and cardiovascular disease prevention, by providing a regular programme of independent review articles covering key aspects of the management of hypertension and cardiovascular diseases. The journal includes: Invited ''State of the Art'' reviews. Expert commentaries on guidelines, major trials, technical advances.Presentation of new intervention trials design.''Pros and Cons'' or round tables on controversial issues.Statements on guidelines from hypertension and cardiovascular scientific societies.Socio-economic issues.Cost/benefit in prevention of cardiovascular diseases.Monitoring of healthcare systems.News and views from the Italian Society of Hypertension (including abstracts).All manuscripts are subject to peer review by international experts. Letters to the editor are welcomed and will be considered for publication.