This was a single-center, retrospective, descriptive study performed to investigate the perioperative serum syndecan-1 concentration in patients who underwent CVS with CPB. This study was conducted using samples stored in a previous study [8].

Ethical approval for this study was provided by the Kobe University Graduate School of Medicine, Medical Ethics Committee (Chairperson Prof. Makoto Nakamura, approval number: B220044) on June 21, 2022.

A trained researcher collected the data and entered the information into a database. Data monitoring and source-data verification were conducted in accordance with a predefined plan. Due to the retrospective nature of the study, the need for informed consent was waived by the ethical committee. Instead, the researchers made appropriate disclosures about the study and provided the participants with the opportunity to refuse enrollment in the study.

Adult patients who underwent CVS with CPB at a national university hospital between March 15, 2016, and August 31, 2020, were included in this study. Patients who were undergoing preoperative dialysis, had preoperative serum creatinine concentrations greater than 2.0 mg dl−1, or who were undergoing surgery involving the descending aorta were excluded.

The following patient characteristics were obtained: age, sex, weight, height, ASA-PS, European System for Cardiac Operative Risk Evaluation II, presence of hypertension and diabetes mellitus, preoperative left ventricular ejection fraction (LVEF), and estimated glomerular filtration rate (eGFR). Surgical information, including operation time, aortic cross-clamp time, duration of CPB, type of procedure, and amount of transfusion during surgery, was also obtained.

Serum syndecan-1 concentrations were measured at the following six time points: (T1) after induction of anesthesia, (T2) 1 h after initiation of CPB, (T3) 2 h after initiation of CPB, (T4) 30 min after weaning from CPB, (T5) 2 h after weaning from CPB, and (T6) postoperative day 1 (Fig. 1). The serum syndecan-1 concentration was measured using an enzyme-linked immunosorbent assay (ELISA) kit (Human CD138 ELISA Kit, Diaclone SAS, France). To prevent observer bias, the serum syndecan-1 concentration was measured by a third party not involved in the study.

Serum syndecan-1 concentration was measured at each time point. The serum syndecan-1 concentration was measured at the following 6 time points: T1) after anesthesia induction, T2) 1 h after initiation of CPB, T3) 2 h after initiation of CPB, T4) 30 min after weaning from CPB, T5) 2 h after weaning from CPB, and T6) on postoperative day 1

Anesthesia was administered by the anesthesiologist in charge. At the facility where this study was conducted, 500 mg of methylprednisolone was administered before starting CPB. Heparin was used as an anticoagulant to control the activated clotting time for more than 400 s, and protamine was administered as a heparin antagonist when hemostasis was confirmed after weaning from CPB. The choice of the type and amount of transfusion and inotropic agent also depended on the anesthesiologist in charge.

Several trained perfusionists controlled the circulatory dynamics during CPB period.

During the CPB procedure, the cardiac index was managed with the target of 2.4–2.6 L/min/m2, and oxygen delivery (DO2) and oxygen consumption (VO2) were monitored as needed.

The primary outcome was the change in the perioperative serum syndecan-1 concentration. The secondary outcome was the association between the perioperative serum syndecan-1 concentration and pAKI incidence. The diagnosis of pAKI was based on the Kidney Disease Improving Global Outcomes classification system. Although AKI was defined as an increase in the serum creatinine concentration and a decrease in urine output, the authors decided not to adopt the criterion of urine output for the definition of AKI in the present study to avoid the influence of the use of a diuretic drug in patients.

All variables are expressed as medians 〔IQRs〕 or means ± SDs. First, the perioperative serum syndecan-1 concentrations were graphically plotted for all patients, and the serum syndecan-1 concentration at each measurement point were compared to that at T1. Comparisons between each measurement point were performed using the Mann‒Whitney U test. The patients were then divided into groups according to the presence or absence of pAKI, and the perioperative serum syndecan-1 concentration was graphically plotted for each group and compared at each time point. Comparisons between two groups were performed using the Mann‒Whitney U test. If the CPB duration was less than 2 h, the serum syndecan-1 concentration at T3 was not measured, and statistical analysis was performed only for those who had data.

A single regression analysis was performed to examine the association between serum syndecan-1 (syndecan-1/10) concentrations and pAKI at each time point. At the time points at which significant differences were detected in the single regression analysis, receiver operating characteristic (ROC) curve analysis was performed to estimate the cutoff value.

The χ2 test was used to analyze whether a serum syndecan-1 concentration above or below the cutoff value had an effect on the occurrence of pAKI.

Finally, multivariate logistic regression analysis was performed to evaluate the association between the serum syndecan-1 concentration and pAKI incidence. No statistical analysis for sample size determination was performed in this study, and a P value < 0.05 was considered to indicate a statistically significant difference. Statistical analysis was performed using SigmaPlot 14.5 (SYSTAT software, CA, United States).