Cardiovascular diseases are among the most serious dangers to human health in the twenty-first century.1 It is predicted that 1.5million cardiac operations are conducted worldwide each year.2 Acute kidney injury (AKI) is a common complication following cardiac surgery.3 A meta-analysis involving 320,086 patients revealed a global incidence rate of 22.3% for AKI associated with cardiac surgery.4 Due to the lack of effective treatment options, postoperative AKI is linked to higher morbidity and mortality, prolonged hospital stays, and increased healthcare expenses,5,6 imposing a substantial burden on patients and healthcare systems. Therefore, it is crucial to detect AKI risk early following cardiac surgery and implement appropriate preventive interventions.

Growing evidence suggests that biomarkers reflecting inflammatory status predict AKI occurrence following cardiac surgery. Increased neutrophil counts and reduced platelet counts have both been implicated in a higher AKI incidence after such procedures.7,8 However, individual indicators can be influenced by confounding variables. Consequently, neutrophil-to-platelet ratio (NPR) has evolved as a composite measure often used to evaluate inflammatory state and immune function in critically ill patients.9 Its predictive value in critical illness and cardiac surgery has also been established. Retrospective studies have indicated that elevated NPR is linked to elevated mortality in patients with acute aortic dissection and infective endocarditis.10,11 Furthermore, NPR can predict postoperative mortality risk in patients undergoing cardiac interventions following myocardial infarction, with higher NPR indicating a rising risk of all-cause mortality.12 Given this context, NPR may also serve as a predictor of AKI risk following cardiac surgery.

Thus, this study intended to delve into associations between NPR and postoperative AKI among patients who had cardiac surgery, utilizing data from Medical Information Mart for Intensive Care (MIMIC), so as to provide clinicians with a more reliable predictor for early screening of patients at high risk for AKI following cardiac surgery.

This study was based on a large intensive care database and systematically explored for the first time the association between NPR and AKI risk within 7 days after cardiac surgery. Our main findings are: (1) Elevated NPR was independently associated with the risk of AKI after cardiac surgery, and there was a dose-response relationship; (2) There was a linear positive correlation between NPR and AKI risk, and no significant nonlinear trend was found; (3) The vast majority (86.9%) of postoperative AKI were early events (occurring within 72h after surgery), highlighting the importance of direct surgical injury; (4) Subgroup analysis revealed that platelet transfusion was an important effector modifier associated with NPR and AKI, and NPR's predictive role in AKI risk was significantly enhanced in patients receiving platelet transfusion.

The pathophysiological mechanism of AKI after cardiac surgery is complex, with inflammatory response and microcirculatory dysfunction considered the core parts.19,20 Our research confirmed that NPR, a comprehensive indicator of neutropenia (representing inflammatory activation) and thrombocytopenia (possibly reflecting consumptive coagulation disease or bone marrow suppression), is a potent predictor of postoperative AKI. After adjusting for a wide range of confounding factors, including demographic characteristics, comorbidities, baseline renal function, and intraoperative and postoperative treatment measures, the AKI risk of patients in the highest NPR triplet (T3) was still 50% higher than that of the lowest group (T1) (OR=1.500). The robustness of this association suggested that the pathophysiological state represented by NPR, namely intense inflammatory storms accompanied by potential microcirculatory hypoperfusion, is independent of other traditional risk factors and directly involved in the pathogenesis of AKI.21 In addition, neutrophils directly cause kidney tissue damage by releasing reactive oxygen species, pro-inflammatory cytokines, and forming neutrophil extracellular traps (NETs).22,23 Thrombocytopenia may be related to sustained microvascular coagulation activation and platelet consumption after surgery, leading to a decrease in renal microcirculation blood flow.24 NPR integrates these two key aspects into a single indicator, which may be more comprehensive in reflecting the environment of AKI occurrence than any single indicator, which may be the reason for its independent predictive ability in multivariate models.

Through analysis of the onset time of AKI, we found a key feature: over 86% of cases occur within 72h after surgery. This highly concentrated time distribution strongly suggests that most postoperative AKIs are driven by direct injuries during the surgery itself and the perioperative process, such as renal ischemia–reperfusion caused by extracorporeal circulation and acute systemic inflammatory reactions induced by surgical trauma.19,25,26 This perfectly matches the characteristics of NPR as a rapidly obtainable inflammatory indicator in the early postoperative period. Our results indicate that NPR can effectively identify patients at risk of early kidney injury due to direct surgical impact, providing strong temporal logic support for its clinical application. In contrast, a small number of late-stage AKIs that occur 72h later may be more caused by postoperative secondary infections or delayed events such as drug nephrotoxicity.27,28 The predictive ability of NPR for this type of late AKI may be limited, which deserves further exploration in future research.

The results of this study are consistent with previous literature. Multiple studies have confirmed that an increase in neutrophil percentage is positively correlated with the risk and mortality of AKI after cardiac intervention,29 and thrombocytopenia is also an independent risk factor for AKI after apical aortic valve implantation30 and aortic dissection surgery.31 This phenomenon exists in both adult and pediatric patients.32 As a comprehensive indicator, the predictive value of NPR has been preliminarily confirmed in the field of heart disease, such as identifying short-term mortality risk (HR=2.37) in patients undergoing cardiac intervention therapy,33 and being associated with in-hospital adverse events (OR=1.602) and long-term adverse prognosis (HR=1.22) after cardiac surgery.34 Further research has shown that in critically ill COVID-19 patients, NPR has a better predictive ability for early AKI than other inflammatory markers.18 These pieces of evidence collectively support the potential of NPR as a comprehensive assessment tool for inflammation and coagulation/microcirculation status. This study provides the first systematic confirmation of the independent association between NPR and AKI in the cardiac surgery population, and further reveals its interaction with platelet transfusion, expanding the clinical applicability of this indicator.

This study found that platelet transfusion significantly enhanced the association between NPR and postoperative AKI risk (P for interaction=0.005). We believe that this phenomenon may stem from the cumulative effect of risk: preoperative high NPR values typically indicate significant inflammatory activation and potential microcirculatory disorders in patients, which constitute the initial high-risk background for AKI. On this basis, although platelet transfusion aims to correct coagulation function,35,36 the transfusion process itself may exacerbate systemic inflammation and renal microcirculation disorders by activating exogenous platelets, promoting their release of more inflammatory mediators and procoagulants.37–39 The combination of these two factors ultimately leads to a significant amplification of the risk of AKI occurrence.

The findings of this study have clear guiding significance for clinical practice. As an easily accessible perioperative inflammatory biomarker, the core value of NPR lies in its ability to identify high-risk patients for AKI after cardiac surgery at an early stage. Subgroup analysis indicates that platelet transfusion is a key factor affecting the association between NPR and AKI. In patients receiving platelet transfusions, the predictive effect of NPR on AKI risk is significantly enhanced, indicating that special attention should be paid to such patients. For high-risk populations identified by NPR, especially those who receive platelet transfusions during surgery, it is recommended to immediately initiate evidence-based AKI prevention bundling strategies. The prudent goal-directed hemodynamic management is required to optimize renal perfusion. Nephrotoxic drugs should be avoided, and special attention should be paid to strict perioperative blood glucose control since our research data also supports the correlation between blood glucose levels and AKI risk. It should be noted that this study has fully considered potential confounding factors such as sociodemographic variables in the statistical analysis. The results showed that even after controlling for these factors, the association between NPR and AKI remained significant and robust, indicating that its predictive value mainly stems from the perioperative inflammatory status it reflects and has independent clinical significance. In summary, by incorporating NPR into the preoperative and early postoperative risk assessment system, the precision of AKI prevention measures can be achieved, the allocation of medical resources can be optimized, and it is expected to improve the postoperative prognosis of cardiac surgery patients.

Our study has a number of drawbacks. First, since this study was a retrospective investigation conducted in a single tertiary medical center, our findings might not be as applicable to different populations or healthcare environments. Our findings will be validated by future multicenter prospective studies with larger sample populations. Second, although we have comprehensively adjusted for multiple known perioperative risk factors, the potential for unmeasured residual confounding factors remains. Notably, cardiopulmonary bypass time represents a critical unadjusted variable, as it is a well-established strong predictor of AKI following cardiac surgery. Furthermore, other potential details that may influence NPR values or renal outcomes, such as specific patient lifestyle factors and medication history (e.g., thrombopoietin, non-steroidal anti-inflammatory drugs), were not incorporated into the analysis due to data availability constraints. Third, considering the intricate connection between inflammation and AKI after cardiac surgery, research should explore additional inflammatory biomarkers and their relationship with AKI, assessing the predictive value of various biomarkers to identify those with greater sensitivity for risk assessment. Lastly, we focused solely on association between NPR and AKI risk within seven days post-surgery. Conducting prospective studies that follow patients and assess relationship between NPR and long-term renal recovery in AKI patients after cardiac surgery would also be important.

Our study revealed that an increase in NPR is associated with an increased risk of AKI within 7 days after cardiac surgery. Subgroup analysis further reveals that the positive association between NPR and AKI risk is significantly enhanced in patients receiving platelet transfusions. As an easily accessible, comprehensive indicator of inflammation, NPR provides valuable clinical tools for early identification of AKI high-risk patients and implementation of targeted prevention strategies, which is of great significance for improving the prognosis of cardiac surgery patients.

Conceptualization: Mingwu Tian, Liqiang Yuan.

Data curation: Jianqiang Wu, Zheng Wang.

Formal analysis: Mingwu Tian, Liqiang Yuan.

Investigation: Zhi Wen, Jianqiang Wu.

Methodology: Zheng Wang, Jian Guo.

Project administration: Changxue Wu.

Resources: Changxue Wu.

Software: Jian Guo.

Supervision: Zheng Wang.

Validation: Zhi Wen.

Visualization: Changxue Wu.

Writing – original draft: Mingwu Tian, Liqiang Yuan, Zhi Wen.

Writing – review & editing: Jianqiang Wu, Zheng Wang, Jian Guo, Changxue Wu.

Not applicable.

This research was supported by Hospital Incubation Project, FHS202407.

The authors declare that they have no competing interests.

Data sharing not applicable to this article as no datasets were generated or analyzed during the current study.