Contrast-induced acute kidney injury (CI-AKI) is impairment in renal function that occurs within days following the intravascular injection of iodinated contrast agents. The pathogenesis of CI-AKI has not been fully elucidated, contrast nephrotoxicity, inflammation, oxidative stress and reactive oxygen species production, as well as renal medullary ischemia have been implicated [1]. The incidence of CI-AKI is generally 3–25%, and can be as high as 30% in patients with acute coronary syndrome [2]. The incidence of CI-AKI in patients with ST-segment elevation myocardial infarction (STEMI) who undergo urgent percutaneous coronary intervention (PCI) is four times higher than that in patients with stable angina [3]. However, periprocedural hydration is currently the primary intervention to mitigate risk, and the benefits of other preventive and therapeutic measures have not been proved [4]. Therefore, early and accurate identification of patients at risk for CI-AKI can help to take appropriate intervention in time to reduce morbidity and mortality [5].

Current CI-AKI prediction models [6] usually required subjective variables, including procedural variables, which compromised the ability of these models to be applied to patients with STEMI treated with emergency PCI. Hence, it is particularly important to find quantitative biomarkers that are more readily available and may serve as predictors for CI-AKI scoring models. Systemic immune-inflammation index (SII) as well as small and dense low-density lipoprotein (sd-LDL) are both clinically accessible and inexpensive quantitative biochemical markers. SII is a novel inflammatory index initially used to predict poor clinical outcomes in various cancers and inflammatory diseases [7], and in recent years studies have found that SII is associated with mortality and prognosis in patients with cardiovascular disease [8]. Sd-LDL is more likely to cause atherosclerosis than LDL, and is an independent risk factor for cardiovascular disease [9]. It has been shown that sd-LDL is also an independent risk factor for CI-AKI in STEMI patients undergoing PCI [10]. The present study aimed to investigate the predictive values of SII, sd-LDL and the combination of both on the risk of CI-AKI after PCI in STEMI patients.

The present study evaluated the value of SII and sd-LDL in predicting the risk of CI-AKI after emergency PCI in STEMI patients. This study found that elevated preprocedural SII (> 1179.07 × 10⁹/L) and sd-LDL (> 1.147 mmol/L) levels in STEMI patients were associated with the development of CI-AKI, and the combination of SII and sd-LDL can be used to assess the risk of CI-AKI in STEMI patients. Additionally, the present study showed that other predictors of development CI-AKI following PCI were advanced age, high uric acid levels, lower LVEF, and lower eGFR. The prediction model for the risk of developing CI-AKI based on these six indicators as predictors showed good discrimination and calibration.

The development of CI-AKI, associated with prolonged hospital stay, treatment costs and short- and long-term mortality, has been an important limitation of angiography with contrast, especially in high-risk patients like STEMI [14]. The occurrence of CI-AKI is currently included as one of the metrics for quality outcomes of PCI [15]. Therefore, proper risk stratification and prevention of CI-AKI after PCI are important from a clinical perspective. Over the past few decades, many different risk scores and markers have been introduced to predict CI-AKI after PCI. The Mehran score [6], which incorporates eight scoring variables including age, diabetes, hypotension, anemia, congestive heart failure, contrast media volume, IABP, and eGFR, or serum creatinine, has had repeated validations. However, it included perioperative variables and excluded patients with acute myocardial infarction. This study constructed a CI-AKI prediction model for STEMI patients undergoing emergency PCI. The predictors were all clinically available quantitative indicators, among which the predictive values of preprocedural SII and sd-LDL levels for CI-AKI were rarely reported. The model showed good interpretability and high predictive accuracy.

Similar to previous studies [16–18], this study found that there was no significant difference in white blood cell count and platelet count between the group with and without CI-AKI, while lymphocyte count was lower, neutrophil count, hs-CRP, NLR and PLR were higher in the CI-AKI group. SII is an indirect inflammatory index that combines peripheral blood platelet count, neutrophil count and lymphocyte count, which can reflect the immune and inflammatory status of patients more comprehensively. It was used to predict mortality in patients with malignancy and acute disease [7], and Esenboğa et al. [19] found that elevated SII was independently associated with no recurrent flow in patients with STEMI undergoing PCI. In a recent study, lnSII > 5.91 × 10⁹/L was one of the independent predictors of the development of CI-AKI after PCI in STEMI patients [20]. The pathophysiological mechanisms between SII and CI-AKI have not been fully elucidated. Previous studies have shown that ischemia, nephrotoxicity and endotoxin-induced AKI are associated with an increase in renal infiltrating neutrophils [21]. When the inflammatory activity of the body increases, the release of large amounts of anti-inflammatory factors leads to apoptosis of lymphocytes and impairment of the body’s immune and antioxidant defenses, resulting in endothelial dysfunction [18]. In addition, platelet activation can activate pro-inflammatory cytokines, leading to collective microcirculation disorders and increased platelet destruction during severe inflammatory responses, resulting in reduced renal blood flow and oxygen supply [22]. Hence, elevated SII levels may influence the development of CI-AKI through inflammatory pathways and overactive coagulation pathways.

Clinical studies have found that sd-LDL is more likely to be phagocytic and transformed into foam cells by macrophages than LDL, and it is difficult to identify and remove, ultimately causing atherosclerosis [23]. Previous studies have also confirmed that oxidized HDL (ox-HDL) and LDL undergo oxidative changes during the progression of renal disease, promoting the formation of small lipoproteins and an increase in oxidized LDL (ox-LDL), with reduced clearance and increased levels of sd-LDL favoring its entry into the arterial wall, leading to renal and vascular damage, causing glomerular obstruction and microcirculatory disturbances, and promoting renal ischemia and hypoxia [24]. In addition, oxidized lipoproteins are more likely to bind to glomerular basement membrane through polyanionic glycosaminoglycans. After glomerular basement membrane damage, a large amount of lipoproteins enter glomerular endothelial cells, which are then presented to foam cells derived from thylakoid cells, macrophages and vascular smooth muscle cells, further aggravating glomerular basement membrane thickening, extracellular matrix expansion, glomerulosclerosis, capillary stenosis and even blockage [25]. Therefore, the renal hemodynamic alterations caused by elevated serum sd-LDL levels may be significant.

The present study showed that advanced age was a risk factor of CI-AKI, which is consistent with other risk scores [14]. The reason may be related to the progressive decline in residual renal function of patients as vascular stiffness increases with age and endothelial function decreases. This study suggests that patients with lower LVEF are more likely to develop CI-AKI, which may be due to organ hypoperfusion caused by chronic ischemia and hypoxia. Long-term low cardiac output exacerbates organ injury, further leading to impaired renal function and poor prognosis [26]. Previous studies have shown a strong relationship between baseline renal function and the risk of CI-AKI, which is further increased after a decrease in baseline renal function [27]. This study also found that with decreased eGFR, patients had a significantly increased risk of CI-AKI. This study indicates that elevated uric acid levels are associated with the occurrence of CI-AKI. When serum uric acid elevated, it was related with vascular endothelial cell dysfunction, inflammation, and renin-angiotensin-aldosterone system (RAAS) activation. Several studies have reported an association between hyperuricemia and the incidence of CI-AKI [28]. In addition, the new Mehran score suggests that contrast dose and hemoglobin are also independent risk factors for CI-AKI [14]. It has been shown that estrogen inhibits erythropoietin production, which inhibits apoptosis, promotes renal tubular epithelial cell regeneration, and ameliorates ischemia- and hypoxia-induced renal injury [29]. Hence, erythropoietin deficiency in hypoglobulinemia patients may lead to further deterioration of renal function [30]. However, the present study did not yield similar results, possibly due to a bias from the significant gender imbalance caused by the larger proportion of male patients in this study. There was no statistical difference between contrast dose and CI-AKI in our study cohort. Previous studies have shown that complications and hemodynamic instability after contrast agent exposure are more associated with AKI than high-dose contrast agent, and that reducing the dose of contrast agent within a certain range does not reduce the risk of CI-AKI [31].

This study also had several limitations that require attention. First, this was a single-center retrospective study, and some patients were excluded due to missing variables, which may be subject to selection bias. Second, the present study failed to compare with other CI-AKI scoring systems, such as the Mehran score. Therefore, multi-center and expanded sample sizes are still needed to further confirm the predictive value of SII and sd-LDL in the development of CI-AKI after emergency PCI in patients with STEMI.

Collectively, the occurrence of CI-AKI after emergency PCI in STEMI patients was associated with age, LVEF, sd-LDL, uric acid, eGFR, and SII levels. The combination of SII and sd-LDL has a high predictive value for CI-AKI after PCI. It provides a reference possibility for clinicians to rapidly identify high-risk and low-risk patients for enhanced or simplified acute kidney injury prevention measures.