A simplified acute kidney injury predictor following endovascular aortic repair: ACEF score

Abstract

Objectives

Treatment of abdominal aortic aneurysms (AAA) with endovascular aortic repair (EVAR) has become quite common in recent years. This method, which has many advantages compared to the open surgical procedure, also has some complications. One of these complications is acute kidney injury (AKI). ACEF (age, creatinine, and ejection fraction) score, which is gaining popularity, can be an easy-to-use and cost-effective method in detecting this condition that causes increased morbidity and mortality. We aimed to evaluate whether this ACEF score may predict a development of AKI in patients who underwent EVAR.

Methods

A total of 133 consecutive patients with AAA who underwent EVAR were analyzed. The primary endpoint of the study was the development of AKI. The best cut-off value for the ACEF score to predict the development of AKI was calculated and according to this value, the patients were divided into two groups as those with high ACEF scores and those with low ACEF scores. ACEF score was calculated by the formula of age/EF + 1 (if baseline creatinine > 2 mg/dL).

Results

After the exclusion criteria, a total of 118 patients were included in the study, and 20 (16.9%) of them developed AKI after EVAR. In the ROC curve analysis, a cut-off value of 1.34 was found for the ACEF score, and scores above this value were found to be independent predictors of AKI development after EVAR. In addition to the ACEF score, the contrast media volume was also found to be an independent predictor of the development of AKI.

Conclusion

In conclusion, ACEF is a simple and effective scoring system in patients undergoing EVAR. To the best our knowledge, our study is the first study which applies ACEF score to predict AKI in EVAR patients.

Keywords

abdominal aortic aneurysm ACEF score acute kidney injury endovascular aortic repair

Introduction

Abdominal aortic aneurysm (AAA) is seen in a wide clinical spectrum ranging from asymptomatic course to rupture.¹ Although open surgical treatment has traditionally been used for many years, the endovascular treatment option is now used as the standard method of AAA treatment.² Although early results provide improvement in parameters such as hospital stay, some complications of EVAR create difficulties in patient management. One of these complications is acute kidney injury (AKI).³ In the development of AKI, mechanisms such as microemboli that may occur during the procedure, the effect of contrast material, and acute tubular necrosis are involved.^4,5 As a result, AKI emerges as an important complication that increases morbidity, length of hospital stay, mortality, and cost.

Many studies have revealed parameters regarding the risk factors for the development of AKI after EVAR.^3,6,7 ACEF score is one of the factors associated with AKI that has been used recently and may develop after an interventional procedure.^8,9 This simple and easy-to-use scoring method, which is calculated by age, creatinine value, and ejection fraction, is a method used to predict mortality in patients who will undergo elective coronary artery bypass grafting.¹⁰ In addition, it has been shown to be associated with mortality and other poor outcomes in percutaneous coronary interventions.⁹ There are publications showing its relationship with mortality and AKI development in TAVR patients.¹¹

Our aim in this study is to determine whether the ACEF score is a predictor of the development of AKI in patients who underwent EVAR.

Methods

Study population

A total of 133 patients who underwent EVAR at our center between January 2014 and June 2020 for abdominal aortic aneurysm were evaluated retrospectively. Emergency procedures (2 patients), ruptured patients (3 patients), patients undergoing dialysis (4 patients), patients who had previous open aortic surgery or EVAR (3 patients), and patients who died during the procedure or within 72 h (2 patients) after the procedure were excluded. After the exclusion criteria, a total of 118 patients were included in the study. The study protocol was approved by the local ethics committee and the study conforms to the principles outlined in the Declaration of Helsinki. Operation was performed by a team consist of two experienced invasive cardiologist, one cardiovascular surgeon, and an anesthesiologist in a sterile environment in the catheterization laboratory. Technical success was defined as nonstenotic renal and hypogastric arteries, avoiding type I and III leakages, absence of iliac stenosis, lower extremities circulation problems, intra-operative mortality, and transformation to open procedure. After the procedure, all patients were followed up in the intensive care unit (ICU).

Data collection

Demographic, clinical, and laboratory characteristics of the patients were recorded from the hospital system. The eGFR values of the patients were calculated with the CockroftGault formula before the procedure. Serum creatinine levels (mg/dL) were measured 24 h before the procedure, immediately after the procedure, and daily until the patient was discharged. Urine output for every patient continues for at least 48 h for every patient in our clinic, and the measurements of output was noted for every patient.

The diagnosis and staging of AKI was performed with the criteria recommended in the second consensus report published by Valve Academic Research Consortium (VARC).¹² The pre- and post-procedural creatinine levels were compared and diagnosis of AKI was made when:

1. Absolute increase in creatinine from baseline ≥ 0.3 mg/dl (≥ 26.4 μmol/L) within 48 h (may increase in time period up to 7 days)

2. Creatinine increased 1.5 times of the baseline value.

The ACEF score was calculated according to the following formula: ACEF = age/left ventricular ejection fraction (%) + 1 (if creatinine was > 2.0 mg/dL).¹⁰ The best cut-off value for the ACEF score to predict the development of AKI was calculated, and according to this value, the patients were divided into two groups as those with high ACEF scores and those with low ACEF scores. The primary endpoint of our study was defined as the development of acute kidney injury after the procedure.

Statistical analysis

Data was analyzed using the Statistical Package for the Social Sciences, version 24.0 (SPSS Inc., Chicago, Illinois, USA). Whether the variables show normal distribution; visual (histograms and probability curves) and analytical methods (KolmogorovSmirnov or ShapiroWilk) were evaluated. Numerical variables showing normal distribution were mean ± standard deviation (SD), and numerical variables not showing normal distribution were expressed as median (interquartile range) and categorical variables as percentage (%). ROC (receiver operating characteristic) curve and Youden index [max (Sensitivity + Selectivity −1)] were used to determine the cut-off value of the ACEF score that best detects the presence of AKI, and the area under the ROC curve over 0.5 was considered significant. Statistical analysis of numerical variables between groups was performed with Student’s t test or Mann–Whitney U test, and analysis of categorical variables with chi-square or Fisher’s exact test. In order to determine the independent predictors of AKI, univariable logistic regression analysis was performed first, followed by a multivariable logistic regression analysis using the parameters that were significant in this analysis. Throughout the present study, a p-value of < 0.05 was considered significant.

Results

We evaluated total of 118 patients, and their mean age was 69.2 ± 7.9 years, and 108 (91.5%) were male and 10 (8.5%) were female. In the tomographic examination performed before the EVAR procedure, the mean maximum diameter of the AAA was 65.7 ± 11.6 mm. In order to determine the cut-off value of the ACEF score that best detects the presence of AKI, the ROC curve was drawn first (Figure 1) and the cut-off value was found to be 1.34 using the Youden index (AUC: 0.810, 95% CI: 0.718–0.903, p < 0.001). Above this cut-off value, AKI could be detected with a sensitivity of 75.0% and a specificity of 79.6. Then, values > 1.34 were accepted as high ACEF scores, and values ≤ 1.34 were accepted as low ACEF scores, and the patients were divided into two groups.

Figure 1.

ROC curve for detecting the development of AKI in patients undergoing EVAR. AUC, area under curves; CI, confidence interval; PPV, positive predictive value; NPV, negative predictive value.

The comparison of the groups in terms of basic characteristics can be seen in Table 1. As expected, patients in the high ACEF group had a higher mean age, higher rates of CHF and CKD, and lower LV ejection fraction and eGFR. In addition, there was a significantly lower mean of albumin in the high ACEF group. In terms of other variables, there was no significant difference between the two groups. Post-procedure AKI developed in 20 (16.9%) patients who underwent EVAR with technical success. As seen in Figure 2, the rates of AKI development were significantly higher in the high ACEF group (42.9%) compared to the low ACEF group (6.0%) (p < 0.001).

Table 1.

Comparison of patients who underwent EVAR according to their ACEF score levels.

	All patients (N = 118)	Low ACEF score (n = 83)	High ACEF score (n = 35)	p-value
Age, years	69.2 ± 7.9	67.1 ± 7.7	74.2 ± 6.2	< 0.001
Male, n (%)	108 (91.5%)	74 (89.2%)	34 (97.1%)	0.278
Body mass index, kg/m²	25.8 ± 3.3	25.7 ± 3.1	25.9 ± 3.8	0.775
Current smoking, n (%)	38 (32.2%)	29 (34.9%)	9 (25.7%)	0.327
Comorbidities
Diabetes mellitus, n (%)	31 (26.3%)	23 (27.7%)	8 (22.9%)	0.584
Hypertension, n (%)	76 (64.4%)	52 (62.7%)	24 (68.6%)	0.539
Coronary artery disease, n (%)	58 (49.2%)	39 (47.0%)	19 (54.3%)	0.469
Congestive heart failure, n (%)	18 (15.3%)	4 (4.8%)	14 (40.0%)	< 0.001
Hyperlipidemia, n (%)	37 (31.4%)	25 (30.1%)	12 (34.3%)	0.656
Cerebrovascular disease, n (%)	5 (4.2%)	4 (4.8%)	1 (2.9%)	1.0
Chronic obstructive pulmonary disease, n (%)	23 (19.5%)	13 (15.7%)	10 (28.6%)	0.106
Chronic kidney disease, n (%)	20 (16.9%)	10 (12.0%)	10 (28.9%)	0.029
LV ejection fraction, %	57.0 ± 8.7	60.8 ± 5.1	48.0 ± 9.0	< 0.001
Laboratory data
Hemoglobin, g/dL	12.67 ± 1.82	12.87 ± 1.81	12.20 ± 1.78	0.067
White blood cells, 10^³/uL	7.79 ± 2.28	7.99 ± 2.41	7.32 ± 1.88	0.143
Platelet, 10^3/uL	228 ± 81	231 ± 89	222 ± 58	0.573
Albumin, g/dL	3.84 ± 0.50	3.93 ± 0.45	3.64 ± 0.57	0.005
Glucose, mg/dL	101 (90–116)	100 (91–116)	102 (89–111)	0.801
Creatinine, mg/dL	1.00 (0.80–1.20)	1.00 (0.81–1.10)	1.03 (0.80–1.50)	0.196
eGFR, mL/min/m²	73 ± 21	77 ± 19	66 ± 24	0.014
C-reactive protein, mg/dL	10 (4–20)	9 (3–16)	13 (5–33)	0.074
AAA diameter, mm	65.7 ± 11.6	64.3 ± 11.7	69.0 ± 10.7	0.042
Procedure-related data
Type of endograft
Medtronic endurant, n (%)	91 (77.1%)	62 (74.7%)	29 (82.9%)	0.790
TriVascular ovation, n (%)	14 (11.9%)	10 (12.0%)	4 (11.4%)
Cook zenith, n (%)	8 (6.8%)	6 (7.2%)	2 (5.7%)
Medtronic talent, n (%)	1 (0.8%)	1 (1.2%)	0 (0.0%)
Vascutec anaconda, n (%)	3 (2.5%)	3 (3.6%)	0 (0.0%)
Gore exluder, n (%)	1 (0.8%)	1 (1.2%)	0 (0.0%)
Operation time, min	146 (103–181)	141 (103–170)	159 (102–207)	0.123
Fluoroscopy time, min	27 (19–35)	25 (18–35)	30 (20–44)	0.137
Contrast media, mL	116 ± 39	115 ± 39	118 ± 38	0.652

Data are presented as percentage, mean ± standard deviation, or median (interquartile range). PCI: percutaneous coronary intervention; CABG: coronary artery bypass graft; LV: left ventricular; eGFR: estimated glomerular filtration rate; LDL-C: low-density lipoprotein cholesterol; HDL-C: high-density lipoprotein cholesterol; AAA: abdominal aortic aneurysm.

Figure 2.

The development of AKI according to the ACEF score in patients who underwent EVAR. AKI, acute kidney injury.

First, univariable logistic regression analysis was performed to identify independent predictors of AKI in patients undergoing EVAR (Table 2). As a result of the analysis, it was determined that albumin, CRP, ACEF score, AAA diameter, and the contrast media volume were associated with AKI. Before these numerical variables were included in the multivariable analysis, ROC curves and Youden index were used and cut-off values were determined and made categorical.

Table 2.

Univariable logistic regression analysis for AKI development.

	Univariable analysis
	OR	95% CI	p-value
Male	1.250	0.245–6.380	0.788
Body mass index	0.982	0.885–1.089	0.729
Current smoking	0.657	0.220–1.963	0.452
Diabetes mellitus	0.923	0.305–2.793	0.887
Hypertension	0.797	0.297–2.137	0.652
Coronary artery disease	1.042	0.398–2.726	0.934
Chronic obstructive pulmonary disease	1.039	0.312–3.467	0.950
Chronic kidney disease	1.844	0.583–5.836	0.298
Hemoglobin	0.944	0.726–1.227	0.666
White blood cells	0.844	0.667–1.069	0.161
Platelet	0.999	0.992–1.005	0.651
Albumin	0.378	0.149–0.954	0.040
Glucose	1.001	0.985–1.018	0.886
C- Reactive protein	1.027	1.004–1.050	0.021
ACEF score	9.748	2.577–36.883	0.001
AAA diameter	1.049	1.010–1.090	0.013
Contrast media	1.014	1.002–1.027	0.024

OR: odds ratio; CI: confidence interval; LDL-C: low-density lipoprotein cholesterol; HDL-C: high-density lipoprotein cholesterol; AAA: abdominal aortic aneurysm.

Multivariable logistic regression analysis was performed with the parameters that were significant in the univariable analysis in Table 3. As a result of the analysis, albumin < 3.86 g/dL (p = 0.271), CRP > 23 mg/dL (p = 0.123), and AAA diameter > 69 mm (p = 0.177) were found to be insignificant, while ACEF score > 1.34 (OR: 9.131, 95% CI: 2.604–32.018, p = 0.001) and contrast media volume >105 mL (OR: 5.914, 95% CI: 1.386–25.237, p = 0.016) were found to be independent predictors of AKI after EVAR.

Table 3.

Multivariable logistic regression analysis for AKI development.

	Multivariable analysis
	OR	95% CI	p-value
Albumin < 3.86 g/dL	2.022	0.577–7.090	0.271
CRP > 23 mg/dL	3.038	0.741–12.465	0.123
ACEF score > 1.34	9.131	2.604–32.018	0.001
AAA diameter > 69 mm	2.353	0.679–8.159	0.177
Contrast media > 105 mL	5.914	1.386–25.237	0.016

OR: odds ratio; CI: confidence interval; CRP: C- reactive protein; AAA: abdominal aortic aneurysm.

Discussion

In this study, we assessed the reproducibility of ACEF score for predicting acute kidney injury in patients who had undergone EVAR treatment. Our main findings of our study are listed below:

1. ACEF score is an independent prognosticator of acute kidney injury in EVAR patients.

2. ACEF score higher than 1.34 predicted acute kidney injury with 75% sensitivity and 79.6% specificity.

Acute kidney injury is a common complication of invasive procedures; however, it is highly related to mortality as well as prolonged hospitalization. Acute kidney injury is simply defined as abrupt decrease of glomerular filtration rate or urinary output or an increase in creatinine levels 72 h after the procedure. Percutaneous endovascular repair is a one of the invasive Figure 3 procedures which may lead to acute kidney injury. Incidence of AKI varies in different studies from 1% to 19%.^13,14 Patients who had open endovascular repair, patients under angiotensin-converting enzyme inhibitor or angiotensin receptor blocker therapy or patients who had > 1000 mL of transfusion after endovascular repair are at risk of development of AKI according to various studies.^3,13,14 Several mechanisms contribute to this condition and are listed as follows: suprarenal fixation of stent which may result in renal artery occlusion, stents which covers accessory renal artery may lead to renal infarction, systemic inflammatory response and ischemia-reperfusion damage, renal embolization because of plaque disruption, contrast-induced nephropathy because of iodine-based contrast, and last but not least ruptured aneurysm repair because of increased oxidative stress and systemic inflammatory response.³

Figure 3.

ACEF score according to the development of AKI in patients undergoing EVAR. AKI, acute kidney injury.

ACEF score is a scoring system which consists of three parameters: age, left ventricular ejection fraction, and creatinine. It is simple and widely used in different patient groups and predicted AKI. Initially, ACEF predicted AKI in patients who underwent percutaneous coronary procedures. According to Ando et al., elder patients with lower ejection fraction and higher serum creatinine levels are at high risk of AKI after percutaneous coronary procedure⁹; on the other hand, isolated low ejection fraction is not found to be related to AKI after procedure. That may demonstrate the importance of using three parameters together instead of evaluation based on just one factor. Following this data, ACEF is used in various patient groups. Uygur et al demonstrated that ACEF score is an independent predictor of AKI in patients following TAVI procedure.¹¹ Moreover, ACEF is a predictor of AKI in patients with acute fulminant myocarditis even if patients do not undergo an invasive treatment.¹⁵ As another example, Chen at al illustrated that ACEF is a predictive value of AKI in patients following coronary bypass graft surgery. Chen et al.⁸ tested five AKI-predicting tests, including ACEF score, STS-mortality, STS-renal failure, EuroScore 1, and EuroScore 2, and ACEF had the best AUROC (area under ROC curve).

The effect of contrast volume on development of acute kidney injury in EVAR patients is controversial. While Sailer et al. reported that iodinated contrast volume is not an independent risk factor for both AKI of long-term worsening for renal function¹⁶; Jin Ho-Mun et al.¹⁷ reported contrast medium volume is a major risk factor in occurrence of AKI after endovascular repair. But still, the amount of contrast volume used in the EVAR procedure cannot predict AKI apart from demographical and clinical characteristics.

The present study has several limitations. First of all, this was a single-center, retrospective study and included a relatively small patient population. Thus, large prospective cohort studies are needed to fully appreciate and validate our findings. Second, there was no standard pre- and post-hydration regimen for patients who underwent EVAR.

Conclusions

Conclusively, ACEF is a simple and effective scoring system in patients undergoing EVAR. To the best our knowledge, our study is the first study which applies ACEF score to predict AKI in EVAR patients. As a result of our results, it would be a correct approach to use semi-strong contrast in patients who underwent EVAR, to pay more attention to hydration before and after the procedure in patients with high ACEF scores, to be more strict in informing about the risk of developing AKI before the procedure, and to follow these patients more closely after the procedure.

Footnotes

Declaration of Conflicting Interests

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The author(s) received no financial support for the research, authorship, and/or publication of this article.

ORCID iDs

Yalcin Avci

Ali Riza Demir

Arda Güler

Kadriye Memiç Sancar

References

Woodrow

Abdominal aortic aneurysms: clinical features, treatment and care. Nurs Stand 2011 Aug 17–23;25(50):50–57; quiz 58.

Salata

Hussain

de Mestral

, et al. Comparison of outcomes in elective endovascular aortic repair vs open surgical repair of abdominal aortic aneurysms. JAMA Netw Open 2019 Jul 3;2(7):e196578.

Saratzis

Goodyear

Sur

, et al. Acute kidney injury after endovascular repair of abdominal aortic aneurysm. J Endovasc Ther 2013 Jun;20(3):315–330.

Saratzis

Melas

Mahmood

, et al. Incidence of Acute Kidney Injury (AKI) after Endovascular Abdominal Aortic Aneurysm Repair (EVAR) and impact on outcome. Eur J Vasc Endovasc Surg 2015 May;49(5):534–540.

Zabrocki

Marquardt

Albrecht

, et al. Acute kidney injury after abdominal aortic aneurysm repair: current epidemiology and potential prevention. Int Urol Nephrol 2018 Feb;50(2):331–337.

Saratzis

Chiocchia

Jiffry

, et al. HYDration and bicarbonate to prevent acute renal injury after endovascular aneurysm repair with suprarenal fixation: pilot/feasibility randomised controlled study (HYDRA Pilot Trial). Eur J Vasc Endovasc Surg 2018 May;55(5):648–656.

Dang

Dakour-Aridi

Rizwan

, et al. Predictors of acute kidney injury after infrarenal abdominal aortic aneurysm repair in octogenarians. J Vasc Surg 2019 Mar;69(3):752–762.e1.

Chen

Chang

Fan

, et al. Comparison of contemporary preoperative risk models at predicting acute kidney injury after isolated coronary artery bypass grafting: a retrospective cohort study. BMJ Open 2016 Jun 27;6(6):e010176.

Andò

Morabito

de Gregorio

, et al. The ACEF score as predictor of acute kidney injury in patients undergoing primary percutaneous coronary intervention. Int J Cardiol 2013 Oct 9;168(4):4386–4387.

10.

Wykrzykowska

Garg

Onuma

, et al. Value of age, creatinine, and ejection fraction (ACEF score) in assessing risk in patients undergoing percutaneous coronary interventions in the ‘All-Comers’ LEADERS trial. Circ Cardiovasc Interv 2011 Feb 1;4(1):47–56.

11.

Uygur

Celik

Demir

, et al. A simplified acute kidney injury predictor following transcatheter aortic valve implantation: ACEF score. Kardiol Pol 2021;79(6):662–668.

12.

Kappetein

Head

Généreux

, et al. Updated standardized endpoint definitions for transcatheter aortic valve implantation: the Valve Academic Research Consortium-2 consensus document. Eur Heart J 2012 Oct;33(19):2403–2418.

13.

Nonaka

Kimura

Hori

, et al. Predictors of acute kidney injury following elective open and endovascular aortic repair for abdominal aortic aneurysm. Ann Vasc Dis 2018 Sep 25;11(3):298–305.

14.

Statius van Eps

Nemeth

Mairuhu

RTA

, et al. Determinants of acute kidney injury and renal function decline after endovascular abdominal aortic aneurysm repair. Eur J Vasc Endovasc Surg 2017 Dec;54(6):712–720.

15.

Liu

Yang

, et al. Predictive value of the age, creatinine, and ejection fraction (ACEF) score in patients with acute fulminant myocarditis. Front Physiol 2021 Feb 24;12:596548.

16.

Sailer

Nelemans

van Berlo

, et al. Endovascular treatment of complex aortic aneurysms: prevalence of acute kidney injury and effect on long-term renal function. Eur Radiol 2016 Jun;26(6):1613–1619.

17.

Mun

Kwon

Park

, et al. Renal function-adjusted contrast medium volume is a major risk factor in the occurrence of acute kidney injury after endovascular aneurysm repair. Medicine (Baltimore) 2021 Apr 9;100(14):e25381.