开放标签、随机、对照、交叉试验：达格列净对接受托伐普坦治疗的ADPKD患者的影响

IF 5.7 2区医学 Q1 UROLOGY & NEPHROLOGY

Kidney International Reports Pub Date : 2025-04-01 DOI:10.1016/j.ekir.2025.01.023

Kiyotaka Uchiyama , Daisuke Kamano , Tomoki Nagasaka , Eriko Yoshida Hama , Ryoichi Shirai , Rena Sumura , Ei Kusahana , Akane Yanai , Takashin Nakayama , Takahide Kimura , Rina Takahashi , Takahiro Kasai , Takaya Tajima , Koji Hosoya , Tatsuhiko Azegami , Shintaro Yamaguchi , Jun Yoshino , Jun Ito , Matsuhiko Hayashi , Takeshi Kanda , Kaori Hayashi

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引用次数: 0

摘要

虽然钠-葡萄糖共转运蛋白2 （SGLT2）抑制剂达格列清可以延缓慢性肾病（CKD）的进展，但其对常染色体显性多囊肾病（ADPKD）患者的作用尚未确定。我们进行了一项开放标签、随机对照交叉试验，以评估达格列净对接受托伐坦治疗的ADPKD患者的附加效应。方法将27例患者随机分为两组，一组接受达格列净10mg治疗，另一组不接受达格列净治疗，为期6个月。主要终点是通过1 - 6个月的线性回归确定的肾小球滤过率（eGFR）的斜率，次要终点包括总肾容量（TKV）的变化。eGFR的计算基于肌酐水平（eGFRcr）、胱抑素C水平（eGFRcys）以及eGFRcr和eGFRcys的平均值（eGFRcr-cys）。结果与未使用达格列净组相比，使用达格列净组eGFRcr-cys和eGFRcys斜率显著降低(2.57±7.88 vs - 5.65±9.57 ml/min / 1.73 m2 /年，P = 0.002；3.91±11.40 vs - 8.43±13.44 ml/min / 1.73 m2 /年，P = 0.003)。同时，在使用达格列净的试验期间，eGFRcr斜率可能适中（1.03±10.78 vs - 3.66±8.88 ml/min / 1.73 m2 /年，P = 0.06）。与不服用达格列净组相比，服用达格列净组6个月TKV变化显著减弱（- 0.44±4.91% vs. 5.04±8.09%,P = 0.01）。结论在接受托伐普坦治疗的ADPKD患者中，达格列净可能具有减缓ADPKD进展的附加效应。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

Open-Label, Randomized, Controlled, Crossover Trial on the Effect of Dapagliflozin in Patients With ADPKD Receiving Tolvaptan

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Open-Label, Randomized, Controlled, Crossover Trial on the Effect of Dapagliflozin in Patients With ADPKD Receiving Tolvaptan

Introduction

Although dapagliflozin, a sodium-glucose cotransporter 2 (SGLT2) inhibitor, delays the progression of chronic kidney disease (CKD), its effect on patients with autosomal dominant polycystic kidney disease (ADPKD) has not been established. We conducted an open-label, randomized controlled crossover trial to evaluate the additive effects of dapagliflozin in patients with ADPKD receiving tolvaptan.

Methods

A total of 27 patients were randomly counterbalanced to receive dapagliflozin 10 mg or usual care without dapagliflozin for 6 months. The primary endpoint was the slope of the estimated glomerular filtration rate (eGFR) determined by linear regression from 1 to 6 months, and the secondary endpoints included changes in total kidney volume (TKV). eGFR was calculated based on creatinine levels (eGFR_cr), cystatin C levels (eGFR_cys), and the mean of eGFR_cr and eGFR_cys (eGFR_cr-cys).

Results

There were significant attenuations in the eGFR_cr-cys and eGFR_cys slopes during the dapagliflozin trial compared with the one without dapagliflozin (2.57 ± 7.88 vs. −5.65 ± 9.57 ml/min per 1.73 m² per year, P = 0.002; 3.91 ± 11.40 vs. −8.43 ± 13.44 ml/min per 1.73 m² per year, P = 0.003, respectively). Meanwhile, the eGFR_cr slope was potentially moderate during the trial with dapagliflozin (1.03 ± 10.78 vs. −3.66 ± 8.88 ml/min per 1.73 m² per year, P = 0.06). The 6-month change in TKV was significantly attenuated during the trial with dapagliflozin compared with the one without dapagliflozin (−0.44 ± 4.91% vs. 5.04 ± 8.09%, P = 0.01).

Conclusion

In patients with ADPKD treated with tolvaptan, dapagliflozin may have an additive effect in slowing ADPKD progression.

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来源期刊

Kidney International Reports Medicine-Nephrology

CiteScore

7.70

自引率

3.30%

发文量

1578

审稿时长

8 weeks

期刊介绍： Kidney International Reports, an official journal of the International Society of Nephrology, is a peer-reviewed, open access journal devoted to the publication of leading research and developments related to kidney disease. With the primary aim of contributing to improved care of patients with kidney disease, the journal will publish original clinical and select translational articles and educational content related to the pathogenesis, evaluation and management of acute and chronic kidney disease, end stage renal disease (including transplantation), acid-base, fluid and electrolyte disturbances and hypertension. Of particular interest are submissions related to clinical trials, epidemiology, systematic reviews (including meta-analyses) and outcomes research. The journal will also provide a platform for wider dissemination of national and regional guidelines as well as consensus meeting reports.