Risk factors for acute kidney injury in elderly patients after coronary artery bypass grafting: A Chinese population

Background: Elderly patients are more likely to have adverse complications after coronary artery bypass grafting (CABG). There are few studies on the risk factors of acute kidney injury (AKI) after surgery in elderly patients, especially in the Asian population. This study retrospectively analyse the risk factors of AKI in Chinese elderly patients after CABG, and establish a risk prediction model to detect these risk factors early and take active intervention measures. Methods: A total of 432 patients were included in this study from 2018 to 2019. AKI was dened according to the Kidney Disease Improving Global Outcomes (KDIGO) criteria. The patients were divided into AKI group and non AKI group. Multivariate logistic regression analysis was used to screen out the factors with P < 0.05. The receiver operating characteristic (ROC) curve was made for the predictive risk model. At the same time, the incidence of complications after CABG was compared between the two groups. Results: Of 432 patients in the study, 119 (27.5%) developed AKI. The estimated glomerular ltration rate (eGFR), ≥ 3 coronary anastomoses, intra-aortic balloon pump (IABP) implantation and ventilation time were independent risk factors for AKI. The area of the ROC curve was (0.702, 95% condence interval (CI) [0.643-0.761], P < 0.001). There were 7 deaths in the AKI group, which was signicantly higher than that in the non AKI group. In addition, in the reoperation and postoperative myocardial infarction, the AKI group was also higher than the non AKI group. Conclusion: The eGFR, ≥ 3 coronary anastomoses, IABP implantation and ventilation time are independent risk factors for AKI in elderly patients undergoing coronary artery bypass grafting. Early discovering these risk factors and taking intervention measures are helpful to reduce the occurrence of AKI after CABG and improve the prognosis of patients.


Background
The incidence of acute kidney injury after CABG is high. According to the de nition of AKI, the incidence rate has been reported from 6.7% to 39% [1][2][3]. It is associated with increased complications and mortality after CABG [3][4][5], and further increases in the more severe stage of AKI; the acute kidney injury after cardiac surgery is independently associated with increased short-term and long-term mortality [4,[6][7][8][9]. It also increases intensive care unit (ICU) length of stay, and resource utilization [2,10].
The development of AKI involves a variety of mechanisms, including ischemic reperfusion injury, renal toxin release, hemolysis, oxidative stress and cytokine secretion, which can cause systemic in ammatory response, endothelial damage and renal tubular cell damage [1,[11][12][13]. Many previous studies have shown that elderly, low ejection fraction, previous kidney history, and long-term cardiopulmonary bypass are important predictors of AKI development [6,[14][15][16].
With the popularization of CABG operations, more and more patients with complications receive CABG treatment. Due to postoperative complications, the results may be unfavorable. Especially for the elderly patients, due to the relatively poor basic renal function of elderly patients, adverse complications after CABG are more likely to occur [17]. However, there are few studies on the risk factors of AKI after CABG in elderly patients, especially in the Asian population. Therefore, this study retrospectively analyzed the risk factors of AKI in Chinese elderly patients after CABG, and established a risk prediction model. Early detecting of these risk factors and taking active intervention measures will help to reduce the occurrence of AKI after CABG and improve the prognosis of elderly patients.

Patients and Setting
A total of 500 patients aged over 70 years who underwent CABG only for the rst time from 2018 to 2019 were included in this study. Among them, 68 cases were lacking in clinical data, and a total of 432 patients were nally included. According to the KDIGO diagnostic criteria of AKI [18], patients were divided into AKI group and non AKI group. There were 119 cases in AKI group and 313 cases in non AKI group.
We promised that our experiment for involving humans was in accordance to guidelines of the Declaration of Helsinki. This study was approved by the Ethics Committee of Beijing Anzhen Hospital (Approval Numbers: 2010043X). Informed consent was obtained from all individual participants included in the study.
De nition of AKI AKI was de ned according to the Kidney Disease Improving Global Outcomes (KDIGO) criteria: an increase in serum creatinine (Scr ≥ 0.3mg/dl), or an increase in Scr ≥1.5times baseline in 7 days after surgery.

Data Collection
Detailed clinical information: this information includes age, gender, body-mass index(BMI), symptom status (New York Heart Association (NYHA) classi cation), previous cardiac history (previous myocardial infarction, and previous percutaneous coronary intervention(PCI)), diabetes, hypertension, hyperlipidemia, peripheral vascular disease, previous stroke or chronic obstructive pulmonary disease, smoking, and baseline renal function (eGFR), left ventricular ejection fraction (LVEF), anemia, proteinuria. The information recorded during the operation included the left main disease, ≥3 coronary artery lesions, ≥ 3 coronary anastomoses, operation time, on-pump CABG, and emergency surgery. Postoperative information included the use of blood products, ventilator time, ICU stay time, and the use of IABP. And related information about surgical complications (death, reoperation, perioperative myocardial infarction, respiratory complications, atrial brillation, stroke) were also included.

Outcome Measures
First, single factor analysis was used to nd out the factors with P value less than 0.02 or clinically closely related to AKI. Then, multivariate logistic regression analysis was used to screen out the factors with P < 0.05. Finally, ROC curve is made for the selected risk factors to obtain the prediction risk model. At the same time, the incidence of complications after CABG was compared between the two groups.
Statistical: SPSS 22.0 for Mac (IBM SPSS Statistics) was used for statistical analyses. Continuous variables were reported as the mean +/− standard deviation or median (interquartile range) (IQR). Categorical variables were reported as the absolute frequency and as a percentage. The Student t-test was applied for continuous data with equal or unequal variances. The Mann-Whitney U test was applied for continuous data that were not normally distributed. Pearson's 2 and Fisher's exact tests were used for categorical data. All meaningful variables were included in a multiple logistic regression analysis. Logistic regression analysis was repeated using variables that were signi cant in the previous analysis [15]. Then the predictive risk model was calculated by the area under the ROC curve analysis. P < 0.05 was considered to be statistically signi cant.

Results
The baseline clinical data on age, sex, body-mass index, smoking, left ventricular ejection fraction, and so on are shown in Table 1. The incidence of AKI was 27.5%. According to the results of univariate analysis and clinical signi cance, the following factors were included in the regression analysis. Age, hypertension, smoking, eGFR, LVEF, anemia, proteinuria, left main disease, ≥3 coronary artery lesions, ≥ 3 coronary anastomoses, IABP implantation , blood transfusion, ventilator time. As shown in Table 2.  Table 3. The area of ROC curve is 0.702, 95% CI [0.643-0.761], P < 0.001. (Figure 1). Postoperative complications indicated that 7 cases died in AKI group, which was signi cantly higher than that in non AKI group (7(5.9%) vs 0(0%) p 0.001. In addition, in the reoperation (10(8.4%) vs 4(1.3%) p=0.001) and postoperative myocardial infarction (34(28.6) vs 26(8.3%) p 0.001, the AKI group was also higher than non AKI group. There was no signi cant difference in other complications between the two groups. As shown in Table 4.

Discussion
Our results suggest that eGFR, ≥ 3 coronary anastomoses, IABP implantation and ventilation time are independent risk factors for AKI in elderly patients undergoing CABG.
Similar to previous studies, the incidence of AKI was 27.5% in our study. The incidence of AKI in elderly patients was lower than that in Wilko Reents' Study [19]. On the one hand, the reason may be that 40% of the patients with renal insu ciency before operation in the Wilko Reents' Study. On the other hand, cardiopulmonary bypass surgery is closely related to acute kidney injury [14], and only 17.1% (74 / 432) of the patients in this study received coronary artery bypass grafting under cardiopulmonary bypass, while more than half of the patients in the Wilko Reents' Study received cardiopulmonary bypass surgery.
Previous studies have shown that preoperative anemia, proteinuria were also independent risk factors for AKI after surgery [20,21]. According to the latest literature, these indicators were included in this study, but the nal results were not consistent with previous studies. On the one hand, the result may not be re ected in the elderly patients, on the other hand, the sample size of this study was not insu cient.
eGFR is a risk factor in this study, which is consistent with many previous studies. IABP implantation is an independent risk factor, which indicates that the use of IABP in elderly patients has greater damage to renal function. IABP implantation is an invasive operation, which will damage the arteries. Moreover, the application of IABP implantation will also increase the use of anticoagulants. These factors together increase the incidence of AKI. In addition, revascularization of more than 3 coronary anastomoses is a protective factor for AKI, which suggests that complete revascularization can not only bene t the heart, but also bene t the renal function. The prolonged ventilator time can increase the incidence of AKI, which suggests that patients can reduce the occurrence of AKI if they can recover from spontaneous breathing as soon as possible. This suggests that preoperative pulmonary function exercise is quite important.
In terms of postoperative complications, the mortality, postoperative myocardial infarction and reoperation in AKI group are higher than those in non AKI group. Previous studies showed acute kidney injury after coronary artery bypass grafting was associated with long-term risk of myocardial infarction. There was 3% -7% of patients undergoing CABG occurring myocardial infarction within one year after surgery [22]. Therefore, our study also suggests that the AKI may be closely related to the occurrence of myocardial infarction, and even affect postoperative death.
The limitations of this study were: on the one hand, this study was a single center, retrospective study, with certain selection bias; On the other hand, the sample size of this study was small, and more samples needed to be included for research and analysed in the future. Finally, in this study, the diagnosis of AKI was based on KDIGO standard. Because many patients have used diuretics after operation, urine volume was not used as one of the diagnostic criteria of AKI.

Conclusions
The eGFR, ≥ 3 coronary anastomoses, IABP implantation and ventilation time are independent risk factors for AKI in elderly patients undergoing coronary artery bypass grafting. Early intervention is of importance. Figure 1 ROC curves using eGFR, ≥3coronary anastomoses, IABP implantation, ventilation time for predicting postoperative AKI