The effects of sodium-glucose transporter 2 inhibition on cardiac surgery-associated acute kidney injury: An open-label randomized pilot study

IF 5 2区医学 Q1 ANESTHESIOLOGY

Journal of Clinical Anesthesia Pub Date : 2025-03-27 DOI:10.1016/j.jclinane.2025.111811

Lars I.P. Snel , Maartina J.P. Oosterom-Eijmael , Elena Rampanelli , Yugeesh R. Lankadeva , Mark P. Plummer , Benedikt Preckel , Jeroen Hermanides , Daniel H. van Raalte , Abraham H. Hulst

{"title":"The effects of sodium-glucose transporter 2 inhibition on cardiac surgery-associated acute kidney injury: An open-label randomized pilot study","authors":"Lars I.P. Snel , Maartina J.P. Oosterom-Eijmael , Elena Rampanelli , Yugeesh R. Lankadeva , Mark P. Plummer , Benedikt Preckel , Jeroen Hermanides , Daniel H. van Raalte , Abraham H. Hulst","doi":"10.1016/j.jclinane.2025.111811","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><div>Sodium-glucose transporter-2 (SGLT2) inhibitors reduced the incidence of acute kidney injury in large cardiovascular outcome trials in patients with chronic heart and kidney failure. Acute kidney injury is a common complication following cardiac surgery. We hypothesized that perioperative SGLT2 inhibition could reduce kidney injury after cardiac surgery, measured with the biomarker neutrophil gelatinase-associated (NGAL).</div></div><div><h3>Methods</h3><div>In this open-label phase IV, randomized, parallel-group, pilot study, adult patients undergoing elective cardiac surgery with cardiopulmonary bypass were randomized to receive either an SGLT2 inhibitor, empagliflozin (10 mg; oral) once daily, from three days before surgery until postoperative day two, or standard-of-care. The primary outcome was the between-group difference of serum NGAL on the second postoperative day. Moreover, other biomarkers for acute kidney injury were measured, including serum kidney injury molecule-1 (KIM-1), hypoxia-inducible factor-1 alpha (HIF-1α), and urine NGAL/Creatinine and KIM-1/Creatinine ratios. Additional outcomes included acute kidney injury incidence within the first seven days following cardiac surgery according to Kidney Disease: Improving Global Outcomes criteria and metabolic parameters, including ketone body concentrations and glycemic control.</div></div><div><h3>Results</h3><div>Between March 2022 and April 2023, 55 patients were included (sex: 73 % male, age: 66 ± 10 years, BMI: 28 ± 4 kg/m<sup>2</sup>, empagliflozin <em>n</em> = 25, control <em>n</em> = 30) in the intention-to-treat analysis. There were no significant between-group differences in serum and urine NGAL or KIM-1. However, empagliflozin significantly reduced the incidence of acute kidney injury (20 % vs 66.7 %; absolute difference 46.7 %, 95 % CI, −69.7 – -23.6; <em>P</em> < .001). A significant increase in serum HIF-1α after surgery was solely observed in the control group. We observed no between-group differences in the incidence of (euglycemic) ketoacidosis or hypoglycemic events.</div></div><div><h3>Conclusions</h3><div>In this pilot study, perioperative SGLT2 inhibition was not associated with lower NGAL levels. We observed that SGLT2 inhibition reduced the incidence of acute kidney injury in this small study population. As the results of this pilot study are hypotheses-generating, further validation is needed in a large-scale, double-blind, placebo-controlled, randomized trial, which is currently ongoing.</div></div>","PeriodicalId":15506,"journal":{"name":"Journal of Clinical Anesthesia","volume":"103 ","pages":"Article 111811"},"PeriodicalIF":5.0000,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Clinical Anesthesia","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0952818025000716","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ANESTHESIOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

Background

Sodium-glucose transporter-2 (SGLT2) inhibitors reduced the incidence of acute kidney injury in large cardiovascular outcome trials in patients with chronic heart and kidney failure. Acute kidney injury is a common complication following cardiac surgery. We hypothesized that perioperative SGLT2 inhibition could reduce kidney injury after cardiac surgery, measured with the biomarker neutrophil gelatinase-associated (NGAL).

Methods

In this open-label phase IV, randomized, parallel-group, pilot study, adult patients undergoing elective cardiac surgery with cardiopulmonary bypass were randomized to receive either an SGLT2 inhibitor, empagliflozin (10 mg; oral) once daily, from three days before surgery until postoperative day two, or standard-of-care. The primary outcome was the between-group difference of serum NGAL on the second postoperative day. Moreover, other biomarkers for acute kidney injury were measured, including serum kidney injury molecule-1 (KIM-1), hypoxia-inducible factor-1 alpha (HIF-1α), and urine NGAL/Creatinine and KIM-1/Creatinine ratios. Additional outcomes included acute kidney injury incidence within the first seven days following cardiac surgery according to Kidney Disease: Improving Global Outcomes criteria and metabolic parameters, including ketone body concentrations and glycemic control.

Results

Between March 2022 and April 2023, 55 patients were included (sex: 73 % male, age: 66 ± 10 years, BMI: 28 ± 4 kg/m², empagliflozin n = 25, control n = 30) in the intention-to-treat analysis. There were no significant between-group differences in serum and urine NGAL or KIM-1. However, empagliflozin significantly reduced the incidence of acute kidney injury (20 % vs 66.7 %; absolute difference 46.7 %, 95 % CI, −69.7 – -23.6; P < .001). A significant increase in serum HIF-1α after surgery was solely observed in the control group. We observed no between-group differences in the incidence of (euglycemic) ketoacidosis or hypoglycemic events.

Conclusions

In this pilot study, perioperative SGLT2 inhibition was not associated with lower NGAL levels. We observed that SGLT2 inhibition reduced the incidence of acute kidney injury in this small study population. As the results of this pilot study are hypotheses-generating, further validation is needed in a large-scale, double-blind, placebo-controlled, randomized trial, which is currently ongoing.

查看原文本刊更多论文

钠-葡萄糖转运蛋白2抑制对心脏手术相关急性肾损伤的影响：一项开放标签随机先导研究

背景：在大型心血管结局试验中，钠-葡萄糖转运蛋白-2 （SGLT2）抑制剂可降低慢性心脏和肾衰竭患者急性肾损伤的发生率。急性肾损伤是心脏手术后常见的并发症。我们假设围手术期抑制SGLT2可以减少心脏手术后的肾损伤，用中性粒细胞明胶酶相关（NGAL）的生物标志物来测量。方法：在这项开放标签、随机、平行组、先导研究中，接受选择性心脏手术合并体外循环的成年患者随机接受SGLT2抑制剂恩格列净(10 mg；口服)每日一次，从手术前三天至术后第二天，或标准护理。主要观察指标为术后第2天血清NGAL的组间差异。此外，还测量了急性肾损伤的其他生物标志物，包括血清肾损伤分子-1 （KIM-1）、缺氧诱导因子-1α (HIF-1α)、尿NGAL/肌酐和KIM-1/肌酐比值。根据肾脏疾病：改善全球结局标准和代谢参数，包括酮体浓度和血糖控制，其他结局包括心脏手术后头7天内的急性肾损伤发生率。结果在2022年3月至2023年4月期间，纳入55例患者（性别：73%男性，年龄：66±10岁，BMI: 28±4 kg/m2，恩格列净n = 25，对照组n = 30）进行意向治疗分析。血清、尿NGAL、KIM-1水平组间差异无统计学意义。然而，恩帕列净显著降低急性肾损伤的发生率(20% vs 66.7%；绝对差异46.7%,95% CI, - 69.7 ~ -23.6；P & lt;措施)。对照组患者术后血清HIF-1α水平明显升高。我们观察到正常血糖酮症酸中毒或低血糖事件的发生率在组间无差异。结论在这项初步研究中，围手术期SGLT2抑制与较低的NGAL水平无关。我们观察到SGLT2抑制降低了这个小研究人群中急性肾损伤的发生率。由于该初步研究的结果是假设生成的，因此需要在目前正在进行的大规模、双盲、安慰剂对照、随机试验中进一步验证。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Journal of Clinical Anesthesia 医学-麻醉学

CiteScore

7.40

自引率

4.50%

发文量

346

审稿时长

23 days

期刊介绍： The Journal of Clinical Anesthesia (JCA) addresses all aspects of anesthesia practice, including anesthetic administration, pharmacokinetics, preoperative and postoperative considerations, coexisting disease and other complicating factors, cost issues, and similar concerns anesthesiologists contend with daily. Exceptionally high standards of presentation and accuracy are maintained. The core of the journal is original contributions on subjects relevant to clinical practice, and rigorously peer-reviewed. Highly respected international experts have joined together to form the Editorial Board, sharing their years of experience and clinical expertise. Specialized section editors cover the various subspecialties within the field. To keep your practical clinical skills current, the journal bridges the gap between the laboratory and the clinical practice of anesthesiology and critical care to clarify how new insights can improve daily practice.