Relationship between perioperative plasma neutrophil gelatinase-associated lipocalin level and acute kidney injury after acute type A aortic dissection

Introduction

Acute type A aortic dissection (ATAAD) is a common and catastrophic cardiovascular surgical emergency. Even with considerable progress in surgical methods and perioperative care, acute kidney injury (AKI) is one of the most prevalent complications during the perioperative period for ATAAD. The incidence of postoperative AKI in ATAAD is approximately 40.1–71.9% (1-3), which is significantly higher than that of other major cardiac surgeries (4,5). Earlier research indicates that AKI following surgery is an independent risk factor for mortality after undergoing ATAAD, which can significantly worsen short and long-term surgical prognoses (3,6). Therefore, early identification of AKI and the implementation of appropriate treatment measures are crucial.

Currently, the detection of AKI primarily relies on observing changes in serum creatinine (sCr) levels and urine output. However, these indicators reflect the balance between the generation of metabolic byproducts and their filtration in the kidneys, which can be influenced by various factors and do not definitively represent the occurrence of AKI. A notable increase in sCr is typically seen only when the glomerular filtration rate drops by over 50%. Its sensitivity in detecting cardiac surgery-related AKI is only around 70% (7,8). Neutrophil gelatinase-associated lipocalin (NGAL) is a group of small molecule proteins secreted by neutrophils and found in the blood and renal tubules, among other tissues, with anti-infection and anti-epithelial cell apoptosis functions (9). Previous studies have revealed that NGAL is one of the transcripts with the most significant upregulation in the kidney during the early occurrence of ischemic, septic or toxic AKI (10). This research concurrently assessed plasma NGAL levels during surgery to forecast the likelihood of postoperative AKI. We present this article in accordance with the STROBE reporting checklist (available at https://jtd.amegroups.com/article/view/10.21037/jtd-24-1804/rc).

Methods

Study populations

From February 2023 to April 2024, a total of 116 ATAAD patients underwent surgical treatment at the Aortic Disease Center of Cardiovascular Surgery Department in Beijing Anzhen Hospital. The diagnostic criteria were established in accordance with the 2022 American College of Cardiology/American Heart Association (ACC/AHA) guidelines for the management of acute aortic syndromes (11), utilizing computed tomography angiography (CTA), and included cases with an onset time of less than 14 days. Among these patients, four were excluded from the study due to death occurring within 24 hours post-operation; two had a preoperative history of chronic renal insufficiency; and blood samples were missing for six patients. Consequently, a total of 104 patients with ATAAD were ultimately included in this study (Figure 1). Preoperative laboratory and imaging data, intraoperative relevant information, and postoperative complications were meticulously recorded and subsequently analyzed. The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. This study received approval from the Medical Ethics Committee of Beijing Anzhen Hospital, Capital Medical University (No. 2022080), and the requirement for informed consent was waived given its retrospective nature.

Figure 1 Flowchart of the study cohort. AKI, acute kidney injury; ATAAD, acute type A aortic dissection.

Blood sample collection and measurement

Routine serological indicators, including sCr, alanine transaminase (ALT), aspartate transaminase (AST), and D-dimer, were assessed in the laboratory department of Beijing Anzhen Hospital. Blood samples from patients were obtained at different time intervals: prior to surgery (T1), at the conclusion of hypothermic circulatory arrest (HCA) during surgery (T2), at the end of cardiopulmonary bypass (CPB) (T3), 24 hours post-operation (T4), and 48 hours post-operation (T5). All blood samples were stored in anticoagulant tubes and promptly centrifuged for 20 minutes at two-thousand rpm or refrigerated at 4 ℃ before being centrifuged within four hours. Plasma supernatants were carefully transferred into Eppendorf (EP) tubes and swiftly stored at −80 ℃ for future analysis. The NGAL tests were performed using commercial reagent kits provided by (Wanlei, Shenyang, China), which supplied analyzers employing a monoclonal antibody-mediated sandwich enzyme-linked immunosorbent assay (ELISA).

Outcome definitions

The primary endpoint of this study is defined as the occurrence of AKI in patients with ATAAD following surgical repair. The secondary endpoints consist of mortality rates, the duration of stay in the intensive care unit (ICU) following surgery and the length of mechanical ventilation. The occurrence of AKI in ATAAD patients after surgical intervention is defined and classified according to the Kidney Disease: Improving Global Outcomes (KDIGO) Acute Kidney Injury Work Group’s 2012 KDIGO criteria. The specific definitions are as follows:

• KDIGO stage 1: an elevation in sCr concentration by ≥0.3 mg/dL within 48 hours, or an increase in sCr to 1.5–1.9 times the baseline level;
• KDIGO stage 2: an elevation in sCr to 2.0–2.99 times the baseline level;
• KDIGO stage 3: an elevation in sCr to 3.0 times the baseline level, or an sCr concentration >354 mmol/L, or initiation of renal replacement therapy (RRT) (12).

Given the potential for immediate anuria following aortic repair surgery in ATAAD patients, urine output will not be utilized as a criterion for diagnosing and classifying AKI within this study. The preoperative estimated glomerular filtration rate (eGFR) will be calculated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation (13).

Organ Malperfusion is defined by the presence of signs or symptoms of organ ischemia, laboratory results supporting the presence of low organ perfusion, or imaging findings indicating the presence of narrowing or reduced enhancement in various systemic branch vessels. Coronary atherosclerotic heart disease is diagnosed based on preoperative CTA records or a history of coronary intervention. According to the 2014 Universal Definition of Perioperative Bleeding (UDPB) in Adult Cardiac Surgery, the amount of intraoperative packed red blood cells (pRBCs) transfusion is classified in detail. We define UDPB level 4 as massive hemorrhage: the volume of pleural effusion exceeds 2000 mL within 24 hours after the operation; the transfusion volume of pRBC exceeds 10 units; the transfusion volume of fresh frozen plasma exceeds 10 units; and recombinant human coagulation factor VIIa for injection is used (14).

Surgical technique

All procedures were carried out with HCA. A median sternotomy was executed to gain access to the thoracic cavity, and CPB was initiated by cannulating the right axillary artery/femoral artery and right atrium. After completing the proximal aortic procedures (Bentall/ascending aortic replacement/David), the nasopharyngeal temperature reached approximately 25–28 ℃, at which point circulatory arrest commenced. The management of the aortic arch involved either total or partial arch replacement. During HCA, cerebral perfusion was provided at a flow rate of 5 mL·kg⁻¹·min⁻¹. In cases of total arch replacement, a four-branch artificial graft was used to reconstruct the main body of the aortic arch, with a stented elephant trunk graft placed into its distal end. After reconstructing the proximal descending aorta, distal perfusion was reinstated. Bilateral cerebral perfusion resumed after reconstruction of the left common carotid artery. Following this, anastomoses for the proximal aorta, left subclavian artery, and brachiocephalic artery were performed in order. For partial arch replacement, once the clamp on the aortic arch was released, trimming occurred up to where it connects with the brachiocephalic artery; then, anastomosis of the distal end of the artificial graft restored continuity within the aortic arch.

Concomitant cardiac procedures are conducted as necessary. In cases where severe coronary perfusion defects or significant coronary artery disease led to circulatory instability, coronary artery bypass grafting (CABG) is performed concurrently. When moderate or greater valvular regurgitation is present, valve replacement or repair is also carried out simultaneously. If the dissection involves the common carotid artery and results in severe cerebral hypoperfusion, concurrent replacement of the common carotid artery is indicated.

Statistical analysis

In this research, quantitative data that follow a normal distribution are reported as mean ± standard deviation. In contrast, for quantitative data that do not adhere to a normal distribution, the results are presented as median and interquartile range. The comparison of quantitative data between the two groups is performed using either the Student’s t-test or the Mann-Whitney U test. A two-way repeated measures analysis of variance (ANOVA) is utilized to analyze the effects of time (T1, T2, T3, T4, T5) and AKI. And a receiver operating characteristic (ROC) curve was employed to assess the predictive capability of the NGAL levels in different timepoint associated with stage 2–3 AKI, and renal malperfusion combined with postoperative stage-3 AKI. Furthermore, we examine the relationship between plasma NGAL levels at different time points and postoperative AKI after ATTAD surgery through a multivariable logistic regression model. Multivariable analyses focus on variables showing P values less than 0.2 in univariable analysis. The preoperative factors are age, times from onset of dissection and operation room, left ventricular ejection fraction (LVEF; %), hypertension, renal malperfusion, D-dimmer and plasma NGAL. And operative factors are aortic valvuloplasty (AVP), ascending aorta replacement, HCA temperature and massive bleeding. Results are expressed as odds ratios (ORs) along with their respective 95% confidence intervals (95% CIs).

Results

Patient and basic characteristics

Based on KDIGO criteria, the incidence of postoperative AKI was 39.4% (41/104). Among the AKI patients, 12 (29.3%) patients were categorized as KDIGO stage 1, 11 (26.8%) as stage 2, 18 (43.9%) as stage 3 and 14 (43.9%) patients required continuous renal replacement therapy (CRRT). Pre-operative characteristics of patients are showed in Table 1. The mean age of AKI group was 52.9±9.7 years old, which is more aged than those in non-AKI group (52.9±9.7 vs. 48.6±11.3 years, P=0.048). In the AKI group, there were 19 male patients, accounting for 46.3%. In the non-AKI group, there were 28 male patients, accounting for 44.4%. There was no statistic difference between the two groups. Additionally, the duration from aortic dissection onset to surgery was significantly earlier in the AKI group compared to the non-AKI group {20 [12, 24] vs. 24 [17, 36] hours, P=0.04}. The incidence of hypertension was higher in the AKI group compared to the non-AKI group [70.7% (29/41) vs. 49.2% (31/63), P=0.03]. No statistic differences between the two groups regarding the prevalence of other comorbidities, including diabetes, chronic obstructive pulmonary disease, hyperlipidemia, cerebrovascular disease, or a history of cardiovascular interventions [percutaneous coronary intervention (PCI) and thoracic endovascular aortic repair (TEVAR)]. Additionally, in terms of preoperative characteristics for ATAAD, the rate of renal malperfusion was notably higher in patients with AKI compared to those without [31.7% (13/41) vs. 9.5% (6/63), P=0.004]. Regarding biomarkers, preoperative plasma NGAL levels were significantly elevated in the AKI group versus the non-AKI group (188.73±56.67 vs. 157.71±42.26 ng/mL, P=0.004). Similarly, preoperative D-dimer levels were also significantly higher among AKI patients than their non-AKI counterparts [538.3 (119.5, 1,361.1) vs. 237.1 (99.6, 369.7) ng/mL, P=0.02]. While the preoperative sCr level was higher in AKI patients and both creatinine clearance (CCr) and eGFR were lower, these differences did not reach statistical significance.

Operative characteristics and postoperative outcomes

The operational specifics and postoperative results are outlined in Table 2. While the majority of surgical methods were comparable between the two groups, the HCA temperature in patients with AKI is lower [24.9 (24.3, 26.4) vs. 25.4 (24.7, 27.7) ℃, P=0.045]. And AVP was more common in patients with AKI [17.1% (7/41) vs. 4.8% (3/63), P=0.047]. Patients with ATAAD who experience massive bleeding during the perioperative period are more likely to have AKI [17.1% (7/41) vs. 4.8% (3/63), P=0.042].

Four patients with AKI after ATAAD surgery died during their hospital stay, while no patients died in the non-AKI group, and it was associated with longer mechanical ventilation duration [28.3 (16.1, 73.9) vs. 16.5 (12.5, 36.0) hours, P=0.01] and prolonged ICU stay [3.4 (1.5, 9.1) vs. 2.3 (1.4, 3.6) days, P=0.02]. The incidence of postoperative complications was higher in the AKI group compared to the non-AKI group, such as respiratory insufficiency [48.8% (20/41) vs. 33.3% (21/63), P=0.005], stroke [22.0% (9/41) vs. 1.6% (1/63), P=0.001], and spinal cord injury [9.8% (4/41) vs. 0% (0/63), P=0.02].

The tendency of plasma NGAL

The trends of NGAL changes are shown in the Figure 2, with the highest values observed before surgery, followed by a gradual decrease. In patients who developed AKI after ATAAD surgery, plasma NGAL levels are significantly higher at all time points compared to patients who did not develop AKI. During our observation period, plasma NGAL decreased gradually, and the trend was the same whether AKI occurred or not. NGAL reached its highest value before surgery (T1) (188.73±56.67 vs. 157.71±42.26 ng/mL, P<0.05). At the end of hypothermia circulatory arrest (T2), NGAL levels were essentially the same as before, with only a slight decrease (179.70±53.75 vs. 152.16±36.78 ng/mL, P<0.05). Then plasma NGAL decreased gradually at each time point. At the end of CPB (T3) plasma NGAL reached (165.93±54.62 vs. 136.07±31.34 ng/mL, P<0.05), 24 hours after surgery (142.97±44.20 vs. 116.66±25.39 ng/mL, P<0.05) and 48 hours after surgery (127.85±37.21 vs. 102.09±23.46 ng/mL, P<0.05). The result of two-way repeated measures ANOVA comparing two groups had a significant difference (P<0.001).

Figure 2 Tendency of plasma NGAL in different time. T1, prior to surgery; T2, at the end of hypothermic circulatory arrest; T3, at the end of cardiopulmonary bypass; T4, 24 hours post-operation; T5, 48 hours post-operation. AKI, acute kidney injury; NGAL, neutrophil gelatinase-associated lipocalin.

Subgroup analysis

The stage-1 AKI was classified as mild AKI (mAKI) and stages 2–3 as severe AKI (sAKI). Prior to surgery, the plasma NGAL levels in patients with sAKI were measured at 200.13±61.09 ng/mL, while those with mAKI had levels of 161.2±31.75 ng/mL. At the conclusion of HCA, the NGAL values for sAKI were recorded at 189.83±57.74 ng/mL, compared to 155.22±33.06 ng/mL for mAKI. Following CPB (T3), the NGAL levels for severe and mAKI were found to be 179.36±58.45 and 133.47±22.96 ng/mL, respectively. At both the 24- and 48-hour postoperative marks, plasma NGAL concentrations in patients with sAKI were observed at levels of 153.13±47.00 and 135.66±39.11 ng/mL, whereas those with mAKI exhibited values of 118.42±23.49 and 108.96±24.31 ng/mL, respectively. At each time point assessed, plasma NGAL in patients with sAKI were significantly higher than those observed in patients with mAKI (P<0.05). However, no significant difference was noted between individuals with mAKI and non-AKI group (Figure 3).

Figure 3 Subgroup plasma NGAL level in different time point. (A) T1: prior to surgery, (B) T2: at the end of hypothermic circulatory arrest, (C) T3: at the end of cardiopulmonary bypass, (D) T4: 24 hours post-operation, (E) T5: 48 hours post-operation. AKI, acute kidney injury; NGAL, neutrophil gelatinase-associated lipocalin.

Plasma NGAL was utilized to predict the occurrence of sAKI following aortic dissection repair, and a ROC was generated (Figure 4). The AUC prior to surgery (T1) was found to be 0.706 (95% CI: 0.582–0.830, P=0.001), with a cut-off value of 219.6 ng/mL, yielding a sensitivity of 93.3% and specificity of 48.3%. The maximum AUC was observed at 48 hours post-surgery (T5). At T5, the AUC increased to 0.739 (95% CI: 0.616–0.861, P<0.001), with a cut-off value of 121.8 ng/mL, resulting in a sensitivity of 80.0% and specificity of 65.5%.

Figure 4 ROC curve for plasma NGAL predict severe AKI. T1: prior to surgery; AUC 0.706 (95% CI: 0.582–0.830, P=0.001). T2: at the end of hypothermic circulatory arrest; AUC 0.697 (95% CI: 0.567–0.826, P=0.002). T3: at the end of cardiopulmonary bypass; AUC 0.722 (95% CI: 0.598–0.845, P<0.001). T4: 24 hours post-operation; AUC 0.732 (95% CI: 0.608–0.856, P<0.001). T5: 48 hours post-operation; AUC 0.739 (95% CI: 0.616–0.861, P<0.001). AKI, acute kidney injury; AUC, area under curve; CI, confidence interval; NGAL, neutrophil gelatinase-associated lipocalin; ROC, receiver operator characteristic.

Furthermore, there were a total of 19 patients with poor renal perfusion. Among them, there were 2 cases of stage-1 AKI, 4 cases of stage-2 AKI, 7 cases of stage-3 AKI (sAKI), and 2 patients required CRRT treatment. Plasma NGAL was used to reflect the severity of renal malperfusion. We employed plasma NGAL at various time points to predict the occurrence of sAKI after surgery in patients with preoperative renal hypoperfusion and plotted the ROC curve (Figure 5). The area under the curve (AUC) prior to surgery (T1) was determined to be 0.772 (95% CI: 0.576–0.967, P=0.02), with an optimum cut-off value of 220.1 ng/mL, which yielded a sensitivity of 71.4% and a specificity of 86.6%. The maximum AUC was observed at 48 hours post-surgery (T5). At T5, the AUC increased to 0.862 (95% CI: 0.753–0.971, P=0.001), with a cut-off value of 152.5 ng/mL, resulting in a sensitivity of 71.4% and a specificity of 90.7%.

Figure 5 ROC curve for plasma NGAL predict renal malperfusion combined with severe AKI. T1: prior to surgery; AUC 0.772 (95% CI: 0.576–0.967, P=0.02). T2: at the end of hypothermic circulatory arrest; AUC 0.769 (95% CI: 0.557–0.982, P=0.02). T3: at the end of cardiopulmonary bypass; AUC 0.809 (95% CI: 0.655–0.962, P=0.006). T4: 24 hours post-operation; AUC 0.828 (95% CI: 0.696–0.959, P=0.004). T5: 48 hours post-operation; AUC 0.862 (95% CI: 0.753–0.971, P=0.001). AKI, acute kidney injury; AUC, area under curve; CI, confidence interval; NGAL, neutrophil gelatinase-associated lipocalin; ROC, receiver operator characteristic.

Independent risk factors and risk prediction of postoperative AKI after ATAAD

In the univariate analysis, age, time from dissection onset to operation, hypertension, preoperative renal hypoperfusion, D-dimer and plasma NGAL were correlated with the postoperative AKI. The univariate analysis during the operation indicated that aortic valve repair, the temperature of circulatory arrest under hypothermia and massive intraoperative hemorrhage might be related to postoperative AKI. The variables mentioned earlier, along with those that exhibited a P value below 0.2 in the univariate analysis, were incorporated into the multivariate logistic regression evaluation. The preoperative factors are age, times from onset of dissection and operation room, LVEF (%), hypertension, renal malperfusion, D-dimmer and plasma NGAL. And operative factors are AVP, HCA temperature and massive bleeding. The results suggested as shown in Table 3 that preoperative LVEF (OR: 0.90, 95% CI: 0.81–0.99, P=0.04), D-dimer level (OR: 1.05, 95% CI: 1.01–1.09, P=0.01), and preoperative plasma NGAL level (OR: 1.02, 95% CI: 1.01–1.04, P=0.01) were independent risk factors for postoperative AKI in patients with ATAAD.

Discussion

ATAAD is a life-threatening aortic condition that can affect multiple organs, and the procedures of total aortic arch replacement or hemi-aortic arch replacement in emergency situations are complex. Consequently, there is a high incidence of perioperative complications involving multiple organs. AKI is among the most common complications linked to ATAAD surgery (15). This study found an AKI incidence rate of 39.4%, with 13.4% of patients requiring CRRT. It is widely acknowledged that AKI following ATAAD may arise from various factors during the perioperative period.

After the occurrence of aortic dissection, blood may accumulate below the renal artery, resulting in inadequate perfusion and leading to acute ischemic kidney injury (16). Several studies have identified preoperative renal malperfusion as an independent risk factor for AKI following ATAAD (17,18). In our cohort, patients with ATAAD who exhibited renal malperfusion prior to surgery were more likely to experience postoperative AKI. Intraoperative factors may exert additional stress on the kidneys. In cardiovascular surgeries requiring CPB, exposure to artificial bypass surfaces, non-pulsatile flow, cross-clamping of the aorta, higher doses of heparin, and hypothermia are associated with inflammatory responses, laminar flow disturbances, cold cardiac ischemia, coagulation issues, and activation of platelets and leukocytes—all of which can contribute to significant acute renal failure (19). The surgical management of ATAAD necessitates prolonged CPB during operations as well as deep HCA; these conditions may activate severe systemic inflammatory responses that elevate the risk of AKI. However, according to research conducted by Englberger et al. and Roh et al., HCA is not considered an independent risk factor for AKI after ATAAD; rather it is the duration of CPB that appears to promote AKI (20,21). Additionally, intraoperative infusion of concentrated red blood cells and hemostatic agents has been shown to disrupt renal microcirculation. In our current study, we found that lower body temperatures did not confer superior protective effects on kidney function; indeed, moderate and deep hypothermia produced comparable outcomes (22,23). Notably, patients who developed postoperative AKI had lower intraoperative circulatory arrest temperatures [24.9 (24.3–26.4) vs. 25.4 (24.7–27.7) ℃].

Excessive bleeding and blood transfusion are significant risk factors for renal dysfunction. We defined mass bleeding as grade 4 based on the UDPB (14), which was identified as a risk factor for AKI in univariate analysis. Evidence suggests that heavy perioperative blood transfusion is a notable characteristic in the bivariate analysis of AKI following total aortic arch replacement (24). Additionally, blood transfusion has been shown to predict prolonged mechanical ventilation after surgery for ATAAD (25). However, the underlying mechanisms remain unclear; it is generally believed that these complications are associated with the inflammatory response triggered by blood transfusions and iron overload (26). Conversely, during clinical practice, numerous hemostatic agents may be administered to patients experiencing significant hemorrhage. This could potentially lead to an increased incidence of thrombosis and disturbances in kidney microcirculation, ultimately resulting in renal insufficiency. In cases where an aortic dissection involves the aortic ring, Bentall surgery or AVP is often indicated. Based on our experience, we have observed that the structural integrity of the aortic root tends to be more stable following Bentall surgery, leading to fewer incidents of bleeding from the aortic root. This observation may correlate with differences in aortic morphology between patients with AKI and non-AKI.

This study found that preoperative levels of D-dimer and NGAL, as well as echocardiographic LVEF, were recognized as independent risk factors for negative outcomes after ATAAD in the multivariate analysis. Another investigation revealed that varying levels of D-dimer prior to surgery can alter coagulation mechanisms during the procedure, leading to increased blood transfusions and the use of hemostatic agents. This cascade may result in acute renal dysfunction necessitating dialysis treatment (27). D-dimer is a specific degradation product of crosslinked fibrin generated by proteolytic enzyme activity and serves as a reliable indicator for assessing coagulation function. While normal individuals exhibit low levels of D-dimer, elevated concentrations are observed in patients experiencing hyperfibrinolysis, hypercoagulability, or fibrin thrombosis (28,29). In the context of ATAAD patients, a marked increase in D-dimer signifies substantial thrombosis within the false lumen and indicates significant consumption of clotting factors. Factors such as CPB and intraoperative bleeding further exacerbate this consumption, resulting in severe hypocoagulation (30). The disruption of the coagulation/fibrinolysis system ultimately leads to diffuse intravascular coagulation (DIC), which impairs renal microcirculation and contributes to AKI. Currently, there is limited research on postoperative AKI among patients with aortic dissection who present with decreased LVEF. Research involving 106 patients who underwent heart valve surgery indicated that an LVEF of less than 45% was an independent risk factor for postoperative AKI (31). Due to their heightened sensitivity to ischemia and hypoxia, patients with decreased LVEF frequently undergo a condition of glomerular hypoperfusion before surgery. Furthermore, during CPB and hypothermic cardiac surgery, additional reductions in renal perfusion may significantly increase the risk of renal injury. After aortic dissection, there is elevation activity of the sympathetic nervous system, which in turn stimulates the renin-angiotensin-aldosterone system (RAAS). This activation results in increased renal vasoconstriction and can lead to prerenal kidney damage (32).

Due to the delay in diagnosing AKI using sCr, many researchers have advocated for improved clinical modalities to enhance AKI diagnosis and assess the severity of NGAL. NGAL is among the most thoroughly researched and promising biomarkers (33,34). It is a protein secreted by activated neutrophils and expressed in various human tissues. NGAL is found in three different forms: renal tubules release a 26 kDa monomer, inflammation cells produce a 45 kDa homodimer, and a 135 kDa complex that forms with matrix metalloproteinase 9 (35,36). In their original study, Mishra found that urinary NGAL levels were significantly increased in the early stages of renal ischemia models and were associated with both the severity and duration of the ischemic event (9). Furthermore, they found that plasma NGAL can be detected within two hours following the onset of AKI, peaking six hours later. The increase in plasma NGAL induced by AKI occurs after the rise in urinary NGAL but precedes any changes observed in creatinine levels by approximately 24 hours (33,36,37). At present, there are no studies confirming the advantages and disadvantages of urine NGAL and plasma NGAL. NGAL can be reabsorbed into the bloodstream after being secreted by renal tubular epithelial cells into the original urine. The increase in plasma NGAL induced by AKI is influenced by several factors. On one hand, the NGAL monomer secreted by renal tubules can be reabsorbed by distal renal tubules. On the other hand, systemic inflammatory responses activate neutrophil aggregation and monocytes, leading to a significant release of NGAL into the bloodstream. Concurrently, renal insufficiency diminishes the clearance capacity for NGAL from circulation, resulting in elevated levels of this biomarker in both plasma and serum (38-40).

Plasma NGAL exhibits a limited predictive capability for simple or mAKI, while demonstrating some predictive value for sAKI. Enhanced predictive accuracy can be achieved when plasma NGAL is integrated with clinical models. Furthermore, NGAL may contribute to the early detection of AKI following ATAAD. However, additional studies are necessary to validate this potential role. The occurrence of AKI after ATAAD is multifactorial and presents unique challenges. Nonetheless, confounding factors can also influence the accuracy of plasma NGAL measurements during its onset. Before being confirmed for clinical application, longer-term clinical studies with larger sample sizes as well as research based on animal models are required to determine the specific mechanism of NGAL changes after ATAAD surgery (33). Notably, NGAL in the bloodstream has an affinity for matrix metalloproteinase 9, a significant substance secreted by endothelial cells during aortic dissection. This interaction may elucidate why plasma NGAL levels peak prior to surgery, irrespective of the presence of AKI. Consequently, it is imperative that biomarkers in blood are evaluated alongside urinary markers to enhance overall predictive efficacy.

Conclusions

The perioperative levels of plasma NGAL in patients who developed AKI after ATAAD were notably elevated compared to those without AKI. Furthermore, plasma NGAL demonstrated strong predictive capability for severe postoperative AKI.

Acknowledgments

None.

Footnote

Reporting Checklist: The authors have completed the STROBE reporting checklist. Available at https://jtd.amegroups.com/article/view/10.21037/jtd-24-1804/rc

Data Sharing Statement: Available at https://jtd.amegroups.com/article/view/10.21037/jtd-24-1804/dss

Peer Review File: Available at https://jtd.amegroups.com/article/view/10.21037/jtd-24-1804/prf

Funding: This work was supported by the Beijing Municipal Science & Technology Commission (No. Z191100006619093) and Beijing Municipal Hospital Research Cultivation Plan Project (No. PX2020024).

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-24-1804/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. This study received approval from the Medical Ethics Committee of Beijing Anzhen Hospital, Capital Medical University (No. 2022080), and the requirement for informed consent was waived given its retrospective nature.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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