The incidence, risk factors and in-hospital mortality of acute kidney injury in patients after abdominal aortic aneurysm repair surgery

Abdominal aortic aneurysm (AAA) is a severe, devastating large artery disease that leads to a high mortality and morbidity, particularly when complicated by aortic rupture [1]. Surgery remains the first-line treatment for AAA, however, postoperative AKI is a major complication associated with poor outcomes [2]. Thus, identification of risk factors associated with postoperative AKI in AAA patients may improve the early monitoring, prevention and treatment of AKI after AAA repair surgery. Over the past decades, studies have reported the prevalence, risk factors and prognosis of postoperative AKI in AAA patients. However, the outcomes of these studies are inconsistent. The Risk, Injury, Failure, Loss of kidney function, and End-stage kidney disease (RIFLE) classification by the Acute Dialysis Quality Initiative group, or the Acute Kidney Injury Network (AKIN) criteria, has been used in most published studies, but results have been conflicting [3‐5]. In 2012, the Kidney Disease Improving Global Outcomes (KDIGO) guideline writing group of the International Society of Nephrology proposed a new AKI criteria by combining AKIN, which has high sensitivity, with the well-stratified RIFLE [6]. However, little has been studied in the Chinese population, although a small sample size with critically ill patients after AAA repair has been reported previously [4]. To better evaluate the relationship between postoperative AKI and AAA repair surgery, we performed a retrospective analysis to define the incidence, risk factors and hospital mortality using the updated KDIGO criteria for classifying the severity of postoperative AKI.

This was a retrospective study including two university hospitals of Sun Yat-sen University in Guangzhou, China: the First Affiliated Hospital and the Sun Yat-sen Memorial Hospital. Patients diagnosed as having AAA and who had undergone AAA surgery between November 1999 and December 2015 were included. The diagnosis of AAA was confirmed by computed tomography angiography (CTA). Exclusion criteria were 1) missing preoperative and postoperative serum creatinine (SCr) data within 7 days, and 2) end-stage renal disease requiring renal replacement therapy. The Institutional Review Boards of the hospitals approved this study and waived the need for informed consent. The study was conducted in accordance with the Declaration of Helsinki [7]. Patients’ medical records and laboratory results throughout the period were reviewed and demographic variables including age, sex and previous medical history (hypertension, diabetic mellitus, cardiovascular disease including coronary artery disease, heart failure and stroke) were recorded. Preoperative variables such as blood urea nitrogen (BUN), SCr and estimated glomerular filtration rate (eGFR) at admission, and the involvement of renal artery and AAA rupture were collected. In addition, the surgical approach, operation duration, blood pressure, volume of intraoperative hemorrhage and the need for vasoactive drugs during surgery were also recorded. Postoperative variables including serum levels of SCr and BUN at 24 h, 48 h and 7 days were collected.

AKI was defined according to the SCr-based criteria of KDIGO published in 2012. The diagnosis of AKI was defined as a SCr increase of ≥26.5 μmol/L within 48 h, or a 1.5-fold increase in SCr within 7 days above baseline value measured on admission. Data on urine output were not available for this study. Baseline eGFR was calculated using the CKD-EPI formula [8]. The severity of AKI was classified into three grades based on the postoperative peak SCr relative to baseline SCr according to the KDIGO criteria.

Our results showed that the incidence of postoperative AKI was 29.9%, and multivariate analysis identified a history of cardiovascular disease, decreased baseline eGFR, involvement of renal artery, ruptured AAA, and OPEN as risk factors of postoperative AKI in all 314 AAA patients undergoing repair surgery. Patients with AKI were at risk for increased in-hospital mortality when compared to non-AKI patients. Moreover, the severity of AKI and ruptured AAA were associated with increased in-hospital mortality in patients with postoperative AKI. Kaplan-Meier analysis showed that improved survival rate was inversely correlated with the severity of AKI in postoperative AKI patients. Importantly, the incidence of AKI was significantly lower in EVAR compared with OPEN. Although OPEN was associated with postoperative AKI, further subgroup analysis found that this increased risk was primarily limited to ruptured, and not nonruptured, AAA patients. Collectively, these findings suggest that EVAR may be a safer approach to AAA repair surgery than OPEN for the prevention of postoperative AKI, especially for patients with ruptured AAA.

In this study, the incidence of postoperative AKI was found to be 29.9%, considerably higher than that reported in the literature [5, 9]. This may be associated with the use of different diagnostic criteria for AKI between this and other studies in which the AKIN or RIFLE criteria were applied and about 9% of AKI patients at the early stage may have been missed by the RIFLE criteria, and 26.9% of AKI patients detected by RIFLE were missed by AKIN [10, 11]. Our results suggested that the KDIGO criteria may be used preoperatively to assess for the risk of postoperative AKI in AAA patients, and may improve early identification and possibly preemptive management of AKI. Unexpectedly, we found that the clinical diagnosis of AKI at the time of hospital discharge was only 2.5%, indicating that AKI may have been markedly underestimated clinically when early diagnosis of AKI was missed.

AKI is an important risk factor associated with long-term mortality of AAA patients [2, 5]. In this study we also found higher in-hospital mortality in AKI patients compared with non-AKI patients after AAA repair surgery (13.8% vs. 3.2%, P < 0.001). In addition, more severe AKI was associated with higher in-hospital mortality and lower survival rate in patients with postoperative AKI. Consistent with previous studies [4, 12‐15], a history of cardiovascular disease, decreased baseline eGFR, renal artery involvement, ruptured AAA, and OPEN were risk factors for postoperative AKI.

While there is a growing body of evidence supporting the use of EVAR as a less invasive approach to achieving better clinical outcomes including a reduction in postoperative AKI compared with OPEN in patients undergoing AAA repair [16, 17], the superiority of EVAR over OPEN remainscontroversial [18‐22]. One study even found that more severe renal impairment occurred in the EVAR compared with OPEN, which may be attributable to atherosclerotic embolization or contrast-induced nephropathy [23]. In this study, we observed a lower incidence of postoperative AKI in AAA patients treated by EVAR when compared with OPEN. This may be associated with less intraoperative hemorrhage, shorter operation time, and less vasoactive drug support in patients treated with EVAR. Although multivariate analysis identified that OPEN was associated with postoperative AKI in all 314 AAA patients (P = 0.036), distinct results were drawn from ruptured or nonruptured subgroup analysis. OPEN was associated with postoperative AKI (OR 23.385, CI 2.564–213.280, P = 0.005) in ruptured but not nonruptured AAA patients. This phenomenon may be partly explained by mild or moderate disease characterized by less intraoperative hemorrhage in nonruptured patients which could not exploit the major advantage of EVAR over OPEN. Thus, EVAR appears to be superior to OPEN in this study in terms of incidence of postoperative AKI for ruptured AAA patients in the prevention of postoperative AKI.

This study has some limitations inherent in a retrospective analysis. First, selection bias, including an unequal number of patients receiving EVAR versus OPEN, a large majority of study participants with mild AKI, and nonrandomized distribution of patients, is inevitable. Second, this study did not collect information on the quantity and type of iodinated contrast agents used in EVAR, and thus, the effects of contrast agents on postoperative AKI in EVAR could not be analyzed. Contrast-induced nephropathy is a serious complication that impacts on survival and recently, even questions about the safety of, and reduced harm from, hypoosmolar iodinated contrast agents have been raised. Post-EVAR AKI might not be directly related to contrast medium but might predominantly be influenced by other factors [24]. Moreover, some studies have demonstrated that iodinated contrast volume is not an independent risk factor for AKI [12, 25]. With the advent of less nephrotoxic iodinated contrast, we believe that the injury effect of iodinated contrast on kidney will gradually become less important. Third, this study had a relatively short period of follow up, which only tracked short-term outcomes. Long-term outcomes of postoperative AKI in AAA patients in this study remain to be documented. Lastly, all 314 patients were not randomly assigned to receive EVAR or OPEN, although the baseline parameters of patients in these two groups were similar. To reduce potential bias caused by these mixed factors, we adopted methods including subgroup analysis to acquire more credible results. In subgroup analysis according to the status of the AAA (ruptured or nonruptured), we demonstrated that OPEN was an important risk factor associated with postoperative AKI in ruptured AAA patients but not in nonruptured AAA patients. A randomized, prospective study in the Chinese population is awaited to confirm whether EVAR is superior to OPEN in minimizing postoperative AKI associated with AAA repair surgery.

This study demonstrates that one-third of AAA patients can develop AKI after aneurysm repair surgery and that the severity of AKI and ruptured AAA status are associated with increased in-hospital mortality in AAA patients who develop postoperative AKI. The incidence of AKI is significantly lower in EVAR compared with OPEN, and OPEN is a risk factor for postoperative AKI particularly in patients with ruptured AAA.