Coronary artery disease (CAD) is commonly associated with multi-organ dysfunction and is recognized as a major contributor to mortality in hospitalized critically ill patients [1, 2, 3]. For patients presenting with left main coronary artery obstructions or three-vessel disease, the primary therapeutic approach for CAD is coronary artery bypass grafting [4]. A major postoperative concern following off-pump coronary artery bypass surgery (OPCABG) is acute kidney injury (AKI), which is associated with increased a common mortality and length of hospital stay [3, 5, 6].

Sodium-glucose cotransporter 2 inhibitors (SGLT2is), including dapagliflozin, represent a novel category of oral medications for diabetes that demonstrate substantial cardiovascular benefits by lowering the incidence of heart failure and mortality among diabetic patients and those with reduced ejection fraction [7, 8, 9]. Emerging evidence suggests these pharmacological agents might effectively mitigate acute kidney injury associated with percutaneous coronary interventions (PCI-AKI) [10]. Multiple systematic reviews have examined both therapeutic outcomes and adverse effects of SGLT2is in patients with acute kidney injury [9, 11, 12]. However, the association between SGLT2 inhibitors and reduced AKI following OPCABG requires further clarification. This research aims to evaluate the potential of SGLT2s in diminishing the risk of OPCABG-AKI and their role in decreasing postoperative mortality.

SGLT2 inhibitors have been a major breakthrough in diabetes treatment, with growing evidence demonstrating their efficacy in delaying eGFR deterioration and protecting against the progression of chronic kidney disease [14, 15, 16, 17]. However, potential associations with the risk of acute kidney injury require careful monitoring [18]. Our investigation of 15,802 coronary artery disease patients receiving off-pump CABG surgery demonstrated that SGLT2 inhibitor use enhanced postoperative renal recovery, lowered mortality rates during hospitalization, reduced the incidence of postoperative atrial fibrillation, and decreased dependency on continuous renal replacement therapy, intra-aortic balloon pumps, and extracorporeal membrane oxygenation, while also shortening overall hospital stays.

Acute kidney injury is generally categorized based on the extent of deterioration of renal function. This classification relies on measuring either the velocity of serum creatinine elevation or urinary output variations observed within 48-hour to 7-day monitoring periods [19]. AKI has now been identified as a significant contributor to increased cardiac complications post-cardiac surgery, progression to chronic kidney disease, and development of end-stage renal pathology. The clinical staging of AKI (grades I–III) substantially influences both patient outcomes and healthcare expenditures [3, 20]. Comprehensive analyses of existing research data are presented in various review articles. A major pooled data study indicates that nearly one-third of coronary artery disease patients receiving off-pump coronary artery bypass grafting developed AKI [21, 22]. The surgical mortality risk approaches 40% in individuals experiencing acute kidney injury during the perioperative period. Multiple investigations have demonstrated strong associations among preserved myocardial performance, preoperative blood glucose management, and whole-body inflammatory responses.

Multiple randomized clinical trials have extensively recorded the effects of SGLT2is on acute kidney injury [23, 24, 25]. Individuals receiving SGLT2 inhibitor therapy showed favorable effects regarding renal outcomes. These medications exhibit enhanced protective capabilities for kidney function among those with acute kidney impairment [23, 24, 25]. Two additional systematic reviews corroborated these findings, revealing that combination therapy with SGLT2 inhibitors in AKI patients having concurrent diabetes resulted in reduced AKI compared to monotherapy approaches [11, 24]. These observations align with previous research outcomes, suggesting potential renal protective benefits of SGLT2 inhibitors against postoperative AKI after off-pump coronary artery bypass grafting. Additional extensive randomized trials are necessary to confirm the therapeutic value of these agents for AKI management following off-pump coronary artery bypass procedures.

Current research predominantly centers around SGLT2 inhibitor applications for AKI management in diabetic populations, where their therapeutic application is well-documented [26], though this specific indication limits broader population generalizations [15]. Emerging findings increasingly highlight the benefits of SGLT2 inhibitors for AKI treatment in non-diabetic cardiac patients, supported by a growing body of clinical evidence [27]. This investigation identified substantial variability when assessing SGLT2 inhibitor efficacy for renal injury in non-diabetic cohorts, potentially stemming from variations in clinical protocols and differential utilization of angiotensin converting enzyme (ACE) inhibitors/angiotensin receptor blockers (ARBs) alongside SGLT2 agents, necessitating judicious clinical application [28, 29]. Comparative analysis demonstrated marginally elevated AKI risk in patients receiving renin-angiotensin system blockers versus those not prescribed these agents [30]. Pharmacological RAS suppression induces vasodilation in efferent renal arterioles, altering glomerular hemodynamics through this mechanism.

In patients undergoing off-pump coronary artery bypass grafting, preoperative administration of sodium-glucose cotransporter-2 inhibitors demonstrated a marked decrease in the occurrence of postoperative acute kidney injury. This nephroprotective effect was observed uniformly across patient subgroups with diverse comorbidities such as chronic hypertension, diabetes, and cardiac insufficiency. The investigation identified that diminished glomerular filtration pressure might potentially elevate the risk of AKI through mechanisms involving preglomerular vasoconstriction and compensatory glomerular expansion mediated by the renin-angiotensin system [31, 32]. The analysis demonstrated that when angiotensin-converting enzyme inhibitors or angiotensin receptor blockers were appropriately adjusted in preoperative regimens, SGLT2 inhibition correlated with improved renal outcomes. The clinical implications of these findings suggest potential applications for SGLT2i utilization strategies in coronary artery disease patients scheduled for cardiac revascularization procedures. However, comprehensive mechanistic studies remain necessary to elucidate the precise pathophysiology of renal impairment associated with SGLT2 inhibition during cardiovascular interventions.

This investigation examined the effects of SGLT2 inhibitors on acute kidney injury development in post-OPCABG patients. Several important constraints merit consideration in this research. The primary methodological restriction stems from the non-randomized design and possible persistence of unmeasured confounding variables, necessitating confirmation through future large-scale randomized controlled trials. Furthermore, the current analysis lacks longitudinal follow-up data to assess patient outcomes over extended periods, highlighting the need for comprehensive RCTs to evaluate chronic prognostic implications. The retrospective observational nature of this work inherently limits mechanistic exploration of therapeutic interventions. Subsequent experimental investigations employing cellular and animal models should focus on elucidating the biological pathways mediating clinical outcomes, as current hypotheses about treatment mechanisms require further substantiation. External validation through additional clinical studies remains essential to confirm the preventive efficacy of SGLT2 inhibitors against AKI in this surgical population. Due to the sample size of the studies included in the Meta-analysis, publication bias could not be completely eliminated through Egger’s test. To address this issue in the future, we will expand the research and increase the sample size to minimize publication bias as much as possible. Finally, although we performed a propensity score-matched analysis in our primary cohort to mitigate confounding, a formal risk of bias assessment for the included studies using standardized tools (e.g., ROBINS-I, Cochrane RoB 2) was precluded by insufficient reporting of methodological details in the original publications. This limitation inherently affects the strength of the conclusions that can be drawn from the meta-analytic results and underscores the need for future high-quality, prospectively designed studies with detailed reporting to confirm these findings.

In patients undergoing OPCABG, preoperative SGLT2i treatment was associated with a significantly reduced risk of postoperative acute kidney injury. This benefit was consistent across subgroups with varying comorbidities including hypertension, diabetes, and heart failure. Our results may be helpful in making decisions regarding the use of SGLT2is in CAD patients before OPCABG. These results need to be verified in future randomized controlled trials.

SGLT2is, Sodium‒glucose cotransporter 2 inhibitors; AKI, acute kidney injury; OPCABG, off-pump artery bypass grafting; CAD, coronary artery disease; PCI-AKI, percutaneous coronary intervention-associated acute kidney injury; BMI, body mass index; eGFR, estimated glomerular filtration rate; Cr, blood creatinine; ICU, intensive care unit; CRRT, continuous renal replacement therapy; PSM, propensity score matching; PRISMA, Systematic Reviews and Meta-Analyses; IABP, intra-aortic balloon pump; Ccr, creatinine clearance; KDIGO, Kidney Disease Improving Global Outcomes; RCTs, randomized controlled trials; ACE, angiotensin-converting enzyme; ARBs, angiotensin receptor blockers.

The data that support the findings of this study are available on request from the corresponding author, [XBY], upon reasonable request.

XZ maintained complete access to all study data and bears responsibility for data reliability and analytical accuracy. Conceptualization and study design were collaboratively developed by XZ, KH, XY and YP. Data collection, processing, and interpretation were conducted jointly by XZ, XY and YP. The initial manuscript preparation was executed by XZ. All participating authors contributed to substantive revisions and intellectual enhancements of the document. Statistical evaluations were performed collaboratively by XZ and YP. Operational support encompassing administrative and technical aspects was provided by XY and KH. Research oversight and guidance were jointly administered by XY and KH. All authors read and approved the final manuscript. All authors have participated sufficiently in the work and agreed to be accountable for all aspects of the work.

Ethical clearance was obtained from the ethics committee at Beijing Anzhen Hospital (2023065X), following the principles of the Declaration of Helsinki. Due to the retrospective nature of the study and the use of de-identified patient data, the requirement for informed consent was waived.

Not applicable.

This research received no external funding.

The authors declare no conflict of interest.

Supplementary material associated with this article can be found, in the online version, at https://doi.org/10.31083/RCM39400.