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Can Renal Resistive Index Predict Acute Kidney Injury After Acute Type A Aortic Dissection Repair?
Hai-Bo Wu, MD, Huai Qin, MD, Wei-Guo Ma, MD, Hong-Lei Zhao, MD, Jun Zheng, MD, Jian-Rong Li, MD, and Li-Zhong Sun, MD Departments of Cardiovascular Surgery and Ultrasound, Beijing Anzhen Hospital of Capital Medical University, Beijing Institute of Heart, Lung and Blood Vessel Diseases, and Beijing Engineering Research Center of Vascular Prostheses, Beijing, China
Background. This study sought to determine whether assessment of the renal resistive index (RRI) can predict the short-term reversibility of acute kidney injury (AKI) after repair of acute type A aortic dissection (TAAD). Methods. This prospective study included 62 patients undergoing repair of acute TAAD. Doppler-based RRIs were obtained preoperatively, immediately after the surgical procedure, and 6, 24, and 48 hours postoperatively. The occurrence of AKI was evaluated daily according to Acute Kidney Injury Network criteria. Persistent AKI was defined as AKI lasting longer than 3 days. The association between the maximum RRI level at different time points and persistent AKI was analyzed by the receiver-operating characteristic curve. Results. Of the 62 patients, 22 (35.5%) had no AKI, 21 (33.9%) had transient AKI, and 19 (30.6%) had persistent AKI. The maximum RRI was 0.67 ± 0.03 (0.62 to 0.71), 0.71 ±
0.05 (0.59 to 0.79), and 0.78 ± 0.05 (0.70 to 0.92) in the no AKI, transient AKI, and persistent AKI groups, respectively. The maximum level of RRI was significantly correlated with that of SCr during the first 48 hours postoperatively (rho [ 0.606; p < 0.001). RRI could predict persistent AKI with an area under the receiver-operating characteristic curve of 0.918 (95% confidence interval, 0.850 to 0.986; p < 0.001). A postoperative RRI of 0.725 or higher was a marker for early detection of persistent AKI with high sensitivity and specificity (94.7% and 72.1%, respectively). Conclusions. An elevated maximum RRI may be a predictor of persistent AKI after repair of acute TAAD. This is helpful for management decision making and improving the prognosis of patients with AKI.
A
Postoperative AKI after repair of acute type A aortic dissection (TAAD) may have several predisposing factors, such as vascular disease, preoperative administration of radiocontrast medium, cardiopulmonary bypass, ischemiareperfusion injury, hemodynamic impairment, systemic inflammatory response, and blood transfusion [8–10]. The early phase of AKI is characterized by alterations in vasoreactivity and renal perfusion [10]. According to Barozzi and associates [11], the renal resistive index (RRI) can assess renal perfusion. In recent years, the RRI as an earlier predictor of AKI has been studied in a wide range of clinical situations [12–15]. Platt and colleagues [16] showed that the RRI may distinguish acute tubular necrosis from prerenal failure. Distinguishing transient from persistent AKI remains clinically relevant as a way to implement and validate adequate therapeutic intervention [17, 18]. Nevertheless, to date there are few data on the role of RRI prediction of AKI in patients with acute TAAD. Because a shorter duration of AKI has been associated with improved long-term survival after cardiac surgical procedures [19], early diagnosis may allow physicians to apply appropriate treatment that could improve prognosis [20]. The objective of this study was to assess value of the RRI measured during perioperative periods in distinguishing transient from persistent AKI in patients after surgical repair of TAAD.
cute kidney injury (AKI) is associated with increased morbidity and mortality rates in patients after aortic surgical procedures [1]. With an incidence of 18% to 55%, AKI affects patients’ prognosis as well as long-term mortality rates, even in patients with partial and complete recovery [2]. Early diagnosis of AKI is difficult simply based on an increase in the level of conventional markers, such as serum creatinine (SCr) level or urinary output [3, 4]. These markers are delayed and unreliable, and they can be affected by several factors during the postoperative period [5]. Newer biomarkers of AKI, such as cystatin C and neutrophil gelatinase-associated lipocalin (NGAL), although more sensitive in earlier detection, have not yet been used routinely [6]. Especially when there is need to choose one or several biomarkers, the clinical relevance, thresholds of significance, and timing for measurement are all parameters to consider in different subsets of patients with AKI [7].
Accepted for publication March 27, 2017. Address correspondence to Dr Sun, Department of Cardiovascular Surgery, Beijing Anzhen Hospital, Capital Medical University, 2 Anzhen Rd, Beijing 100029 China; email: [email protected].
Ó 2017 by The Society of Thoracic Surgeons Published by Elsevier Inc.
(Ann Thorac Surg 2017;104:1583–9) Ó 2017 by The Society of Thoracic Surgeons
0003-4975/$36.00 http://dx.doi.org/10.1016/j.athoracsur.2017.03.057
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Can Renal Resistive Index Predict Acute Kidney Injury After Acute Type A Aortic Dissection Repair?
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Patients and Methods
Table 1. Classification of Acute Kidney Injury Network
The Ethics Committee of Beijing Anzhen Hospital approved this study and waived the need for individual informed consent.
Stage 1
Patients A prospective, observational study was conducted between April and July 2016 in patients with acute TAAD who underwent a total arch replacement and frozen elephant trunk implantation (TAR and FET). The surgical procedure was performed using deep hypothermic circulatory arrest and selective antegrade cerebral perfusion [21]. Inclusion criteria were acute TAAD in patients who were older than 18 years of age. Exclusion criteria were a history of preoperative renal replacement therapy, age younger than 18 years, pregnancy, or death occurring within 48 hours postoperatively.
Diagnostic Criteria for Postoperative Acute Kidney Injury A routine hospital immunoenzymatic method was used to measure SCr. An assessment of SCr value was made preoperatively and daily postoperatively. Postoperative AKI was diagnosed according to the criteria of the Acute Kidney Injury Network (AKIN) [22], which are shown in Table 1. The AKI criteria comprised the following: (1) an absolute increase in SCr of 0.3 mg/dL (26.4 mmol/L) or greater; (2) a percentage increase in SCr of 50% or greater; or (3) urine output less than 0.5 mL/kg/h for 6 hours or longer.
Study Protocol Demographic, intraoperative, and postoperative data were recorded prospectively. The RRI was measured on the day before the operation, immediately afterward, and at 6, 24, and 48 hours postoperatively. Recovery from AKI was defined as a 50% decrease in SCr or a return of SCr to its measured or estimated baseline level, or both [15, 23]. Transient AKI was defined as recovery from AKI within 3 postoperative days. Persistent AKI was defined as persistent elevation of SCr after 3 postoperative days.
Measurements of the Renal Resistive Index Doppler-based RRI measurement was obtained from a posterolateral approach [11, 24] by using a transparietal 5-MHz pulsed-wave Doppler probe (GE Vivid E9, Horten, Norway). The RRI was calculated using the following equation: RRI ¼
Peak systolic velocity – End diastolic velocity Peak systolic velocity
The best option for measuring the RRI is the arcuate arteries, and measurements were obtained using pulsewave Doppler imaging [25]. Two expert echocardiographers performed the examinations and served as controls for each other. The RRI was tested three times by two investigators in 10 patients preoperatively to evaluate interobserver variability (mean, 0.001; SD 0.013; p ¼ 0.811). The minimum and maximum Doppler shifts were
2 3
Serum Creatinine
Urine Output
Increase of 0.3 mg/dL (26.4 <0.5 mL/kg/h for >6 h mmol/L) or increase of 150%–200% (1.5- to 2-fold) from baseline Increase of>200%–300% (>2- <0.5 mL/kg/h for >12 h to 3-fold) from baseline Increase of >300% (>3-fold) <0.3 mL/kg/h for 24 h or anuria for 12 h from baseline (or value of l4.0 mg/dL[354 mmol/L] with an acute increase of >0.5 mg/dL [44 mmol/L]) or need for renal replacement therapy
recorded. A reading was considered satisfactory once three consecutive similar waveforms were obtained and the average of three measurements was taken. The RRI then was calculated as the average RRI for each kidney.
Statistical Analysis Data were analyzed with SPSS for Windows version 20.0 (IBM Corp, Armonk, NY). Continuous and categorical variables are expressed as mean SD (or median and range) and the number and percentage of patients, as appropriate. The c2 test was used to identify univariate predictors for AKI. Receiver-operating characteristic curves were constructed to assess the diagnostic value of the RRI. The optimal cutoff was first assessed by Youden’s index (J ¼ Sensitivity þ Specificity 1). Linear regression analysis was used to assess the correlation between the maximum levels of RRI (RRImax) and SCr. All analyses were two-sided, and any p value of <0.05 was considered statistically significant.
Results Among the 73 patients undergoing TAR and FET for repair of acute TAAD during the study period, 11 patients were excluded (1 for arrhythmia, 2 because they died during the first 48 hours postoperatively, 7 for incomplete data, 1 for pregnancy), and 62 patients were included in this study, as shown in Figure 1. Among the 62 patients, 22 (35.5%) patients presented with no AKI, transient AKI developed in 21 (33.9%), and 19 (30.6%) had persistent AKI, 12 of whom required dialysis. Patients’ characteristics were similar among patients with no AKI, transient AKI, and persistent AKI, except for the SCr (p ¼ 0.037) before operation (Table 2). Thirteen of 19 patients with persistent AKI had neurologic complications, and spinal cord injury occurred in 1 patient (1.6%; 1 of 62). Five patients with persistent AKI died within 30 days after the surgical procedure. The postoperative rates of neurologic complications and mortality were significantly different between patents with persistent AKI and patients with transient and no AKI (p < 0.001 and p ¼ 0.001, respectively) (Table 2). The RRImax differed significantly among patients with no AKI,
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p < 0.001). Continuous renal replacement therapy was eventually required in 12 of 19 patients with persistent AKI compared with the 43 other patients (p < 0.001). The areas under the receiver-operating characteristic curve (AUC) of preoperative SCr was 0.659 (95% confidence interval, 0.510 to 0.809; p ¼ 0.047). The AUC of RRImax was 0.918 (95% confidence interval, 0.850 to 0.986; p < 0.001). The AUC of RRImax showed a higher value to predict persistent AKI (p < 0.001) (Fig 2). RRImax had a sensitivity of 94.7% and a specificity of 72.1%. The cutoff of RRImax for diagnosing persistent AKI was 0.725.
Fig 1. Flow chart of the study. (AKI ¼ acute kidney injury; postop ¼ postoperative; TAAD ¼ type A aortic dissection; TAR þ FET ¼ total arch replacement and frozen elephant trunk implantation.)
transient AKI, and persistent AKI (0.67, 0.71, 0.78, respectively; p < 0.001). The level of preoperative RRI did not differ among the groups with no AKI, persistent AKI, and persistent AKI. However, the level of RRI significantly increased in patients with postoperative AKI compared with patients without AKI (p < 0.001). Linear regression analysis detected a significantly positive correlation between RRImax and SCr during 2 days postoperatively (rho ¼ 0.606;
Correlation of Kidney Perfusion with Development of Acute Kidney Injury Preoperative computed tomography scans showed that the dissection extended to the suprarenal abdominal aorta in 17.7% (11 of 62) and the iliac artery in 82.3% (51 of 62), a finding that did not differ among three groups (p ¼ 0.816). Bilateral kidney perfusion from the true lumen was observed in 63.6% (14 of 22), 52.4% (11 of 21), and 47.4% (9 of 19), and unilateral kidney perfusion from the true lumen was noted in 36.4% (8 of 22), 47.6% (10 of 21), and 52.6% (10 of 19) of patients with no AKI, transient AKI, and persistent AKI, respectively (Table 3). Perfusion of both kidneys from the false lumen was not observed in the cohort. However, in a 57-year-old man with an aortic
Table 2. Preoperative, Operative, and Postoperative Data Variable Demographic data Male Age (y) Body mass index (kg/m2) Medical history Hypertension Diabetes Marfan syndrome Cerebrovascular disease COPD Smoking Preoperative SCr (mmol/L) Preoperative RRI Operative data CPB time (min) Cross-clamp time (min) DHCA time (min) RBC use (unit) Postoperative results Postoperative RRImax CRRT Neurologic complications Reexploration for bleeding Operative mortality
Total (N ¼ 62) (%)
No AKI (n ¼ 22) (%)
Transient AKI (n ¼ 21) (%)
Persistent AKI (n ¼ 19) (%)
51 (82.3) 47.3 11.3 26.2 3.5
19 (86.4) 43.1 10.1 25.3 3.2
17 (81.0) 47.9 11.2 26.6 3.5
15 (78.9) 51.5 11.5 26.5 3.8
0.818 0.055 0.399
17 1 2 1
p Value
45 (72.6) 2 (3.2) 4 (6.5) 3 (4.8) 2 (3.2) 29 (46.8) 90.7 43.5 0.65 0.05
(77.3) (4.5) (9.1) (4.5) 0 10 (45.5) 84.1 23.8 0.63 0.04
15 (71.4) 1 (4.8) 1 (4.8) 0 2 (9.5) 11 (52.4) 78.7 22.3 0.65 0.04
13 (68.4) 0 1 (5.3) 2 (10.5) 0 8 (42.1) 111.5 67.2 0.66 0.07
0.399 0.645 0.827 0.311 0.137 0.808 0.037 0.063
233.8 51.1 137.5 33.9 23.7 8.1 5.6 4.1
219 35 129 30 27 10 4.9 4.2
241 59 142 36 26 7 5.1 4.3
241 56 141 36 21 6 6.8 3.7
0.271 0.402 0.078 0.261
0.72 0.06 12 (19.4) 20 (32.3) 4 (6.5) 5 (8.1)
0.67 0.03 0 3 (13.6) 0 0
0.71 0.05 0 4 (19.0) 3 (14.3) 0
0.78 0.05 12 (63.2) 13 (68.4) 1 (5.3) 5 (26.3)
<0.001 <0.001 <0.001 0.163 0.001
AKI ¼ acute kidney injury; COPD ¼, chronic obstructive pulmonary disease; CPB ¼ cardiopulmonary bypass; CRRT ¼ continuous renal replacement therapy; DHCA ¼ deep hypothermic circulatory arrest; RBC ¼ red blood cell; RRI ¼ renal resistive index; SCr ¼ serum creatinine.
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patients and 3 survivors in the persistent AKI group) showed that perfusion of the kidneys at 3 months did not change compared with preoperative findings (Table 3).
Comment The main finding of our study was the ability of postoperative RRImax to predict persistent AKI with a high level of sensitivity (94.7%) and specificity (72.1%) at an early stage after repair of acute TAAD. This finding implies that Doppler-based RRI may be a promising tool in assessing chances for renal recovery. Brown and colleagues [26] demonstrated a direct correlation between duration of AKI and long-term mortality rates. Early recovery of renal function after cardiac surgical procedures has been shown to improve long-term survival [19]. Measurement of renal velocity by Doppler ultrasound is a noninvasive and rapid surrogate method that allows the instantaneous assessment of parenchymal renal perfusion [24, 27], as well as the differentiation of transient from persistent AKI. Darmon and associates [15] showed that an elevated RRI greater than 0.795 predicted persistent AKI with 82% sensitivity and 92% specificity in critically patients who required mechanical ventilation. A meta-analysis by Ninet and associates [28] also showed that an elevated RRI was associated with the reversibility of AKI in critically ill patients with severe sepsis, cardiac surgical procedures, mechanical ventilation, or diagnosed AKI. Differentiating persistent AKI from transient AKI may be helpful in treatment decision making. However, the role of the RRI in the shortterm therapeutic regimen of AKI has to await further validation in larger series, especially in patients undergoing other cardiac surgical operations. Early intervention for AKI is definitely associated with lower costs, shorter hospital stays, and better outcomes. In this study, the incidence of persistent AKI was 30.6%, and 19.4% of patients required dialysis. These results are similar to the overall incidence found in our department in patients undergoing repair of acute TAAD [29]. After acute aortic dissection, the mechanisms of AKI mainly
Fig 2. Receiver-operating characteristic of serum creatinine before the operation and maximum renal resistive index (RRImax, the maximum renal resistive index measured at different time points: immediately after the surgical procedure and at 6, 24, and 48 postoperative hours). (AUC ¼ areas under receiver-operating characteristic curve; pre-SCr ¼ preoperative serum creatinine.)
arch entry tear, the left kidney was perfused from the true lumen, whereas the right kidney was perfused from both the true and false lumina. The perfusion of both kidneys remained unchanged postoperatively in this patient (Fig 3). Although perfusion from the true lumen did not differ among the three groups (p ¼ 0.558), one-kidney perfusion from the true lumen was found to be associated with a significantly higher mortality rate for the entire cohort (5 of 30 vs 0 of 32; p ¼ 0.022) and for patients with persistent AKI (5 of 10 vs 0 of 9; p ¼ 0.033). Follow-up computed tomography scans, available in 54 patients (excluding 5 deceased Table 3. Extension of Dissection and Kidney Perfusion Variable Extension of dissection Suprarenal abdominal aorta Iliac artery Perfusion of kidney Preoperative CTA One kidney from true lumen Both kidneys from true lumen Postoperative CTA One kidney from true lumen Both kidneys from true lumen
Total (N ¼ 62) (%)
No AKI (n ¼ 22) (%)
Transient AKI (n ¼ 21) (%)
Persistent AKI (n ¼ 19) (%)
11 (17.7) 51 (82.3)
3 (13.6) 19 (86.4)
4 (19.0) 17 (81.0)
4 (21.1) 15 (78.9)
28 (45.2) 34 (54.8) (n ¼ 54) 20 (37.0) 34 (63.0)
8 (36.4) 14 (63.6) (n ¼ 22) 8 (36.4) 14 (63.6)
10 (47.6) 11 (52.4) (n ¼ 21) 10 (47.6) 11 (52.4)
10 (52.6) 9 (42.1)a (n ¼ 11)b 2 (18.2) 9 (81.8)
p Value 0.816
0.558
0.261
a b In 1 patient, the right kidney was perfused from both the true and false lumina (Fig 3). Five patients died postoperatively, and 3 of 14 survivors did not have follow-up CTA scans; at 3 months, CTA scan was available in only 11 patients with persistent AKI.
AKI ¼ acute kidney injury;
CTA ¼ computed tomographic angiogram.
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Fig 3. Computed tomography in a patient with arch entry tear, (A) the right kidney was perfused from both the true and false lumina, whereas (B) the left kidney was perfused from the true lumen. (C, D) The perfusion of both kidneys remained unchanged at 3 months after ascending aortic and total arch replacement with frozen elephant trunk implantation.
include two categories: prerenal or intrinsic [5]. Prerenal AKI resulting from decreased renal perfusion is reversible. There is a pathophysiologic continuum from transient AKI to persistent AKI, so prompt recognition and rapid restoration of renal perfusion may prevent or attenuate acute tubular necrosis [30]. In patients with persistent AKI, avoiding potentially deleterious interventions and promptly starting renal replacement therapy may improve outcomes [15, 31, 32]. Our RRI threshold of 0.725 for predicting persistent AKI after repair of acute TAAD is similar to that found in human septic shock and approaches the predictive values (RRI >0.70) reported in humans and in a rabbit model of AKI. Guinot and colleagues [20] reported that an RRI threshold value greater than 0.73 can distinguish transient from persistent AKI after cardiac surgical procedures. Indeed, the RRI is used for assessing instant renal perfusion, which only subsequently leads to accumulation
of SCr and reduced urine output [33]. Routine evaluation of the RRI in patients at risk for AKI could encourage clinicians to maximize renal-sparing measures such as reestablishment of renal perfusion and initiation of preventive therapies to attenuate acute tubular necrosis [15]. Moreover, the RRI is correlated with the severity of renal dysfunction. Such a prompt response to AKI would not be possible if the therapeutic strategy is based on delayed criteria, such as the increase in SCr or sustained oliguria. Therefore the development of a marker allowing for early detection of AKI may help clinicians prevent persistent AKI in patients with transient AKI [17]. In this study, the levels of preoperative RRI were similar in patients who subsequently developed AKI and in those without postoperative AKI. A lack of correlation between RRI and SCr before kidney injury was previously noted in patients with septic shock [14]. This finding suggests that the RRI is a distinct marker of AKI,
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rather than a reflection of preexisting chronic renal insufficiency. Beyond its ability to predict the reversibility of AKI, the RRI has several advantages: rapidity, portability, realtime imaging, high feasibility, simplicity, ease of use, and capability of repeated assessments [34]. Thus the RRI may become a useful tool for adjusting management decisions based on the severity of AKI at the bedside by providing information about renal perfusion [20].
Study Limitations The sample size was relatively small in this single-center experience. The average age of patients was much younger compared with Western series, and all patients underwent TAAD repair with the FET technique; patients undergoing other aortic procedures such as isolated total arch replacement (without an FET) were not included. Nor were long-term data on morbidity or mortality available in this cohort. The RRI depends on several interrelated parameters (vascular resistance and heart rate). Indeed, increased vascular resistance and decreased heart rate were shown to raise the RRI. Some studies indicated that the RRI could be influenced by mean arterial pressure [14], vascular compliance, pulse pressure [35, 36], oxygen level [37], or intraabdominal pressure [38]. These factors were not taken into consideration in our study. We purposely excluded patients with arrhythmia from this study. Thus we assume that the dependence of RRI on heart rate was sufficiently controlled to limit the bias in the RRI assessment. Additional prospective studies are warranted to assess potential confounders more accurately. Despite the vagaries of the RRI measurement and its possible inaccuracies related to hemodynamic issues, RRI may be helpful in detecting and treating AKI earlier and be included among the postoperative diagnostic techniques to improve patients’ outcomes. AKI after major cardiac and thoracic aortic operations is one of the most difficult complications to avoid. Future studies will allow for identifying patients with impending AKI earlier, intervening on time, and then hopefully decreasing the rate of AKI.
Conclusions This study showed that the RRImax during the first 48 postoperative hours could predict persistent AKI after surgical repair of acute TAAD with good sensitivity and specificity. Determination of RRI with Doppler sonography is feasible and may be helpful in the diagnosis of persistent AKI.
This study was supported in part by the National Key Technologies Research and Development Program (Grant 2015BA112B03) and Special Research Fund for Public Health and Welfare (Grant 201402009).
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Background. This study sought to determine whether assessment of the renal resistive index (RRI) can predict the short-term reversibility of acute kidney injury (AKI) after repair of acute type A aortic dissection (TAAD). Methods. This prospective study included 62 patients undergoing repair of acute TAAD. Doppler-based RRIs were obtained preoperatively, immediately after the surgical procedure, and 6, 24, and 48 hours postoperatively. The occurrence of AKI was evaluated daily according to Acute Kidney Injury Network criteria. Persistent AKI was defined as AKI lasting longer than 3 days. The association between the maximum RRI level at different time points and persistent AKI was analyzed by the receiver-operating characteristic curve. Results. Of the 62 patients, 22 (35.5%) had no AKI, 21 (33.9%) had transient AKI, and 19 (30.6%) had persistent AKI. The maximum RRI was 0.67 ± 0.03 (0.62 to 0.71), 0.71 ±
0.05 (0.59 to 0.79), and 0.78 ± 0.05 (0.70 to 0.92) in the no AKI, transient AKI, and persistent AKI groups, respectively. The maximum level of RRI was significantly correlated with that of SCr during the first 48 hours postoperatively (rho [ 0.606; p < 0.001). RRI could predict persistent AKI with an area under the receiver-operating characteristic curve of 0.918 (95% confidence interval, 0.850 to 0.986; p < 0.001). A postoperative RRI of 0.725 or higher was a marker for early detection of persistent AKI with high sensitivity and specificity (94.7% and 72.1%, respectively). Conclusions. An elevated maximum RRI may be a predictor of persistent AKI after repair of acute TAAD. This is helpful for management decision making and improving the prognosis of patients with AKI.
A
Postoperative AKI after repair of acute type A aortic dissection (TAAD) may have several predisposing factors, such as vascular disease, preoperative administration of radiocontrast medium, cardiopulmonary bypass, ischemiareperfusion injury, hemodynamic impairment, systemic inflammatory response, and blood transfusion [8–10]. The early phase of AKI is characterized by alterations in vasoreactivity and renal perfusion [10]. According to Barozzi and associates [11], the renal resistive index (RRI) can assess renal perfusion. In recent years, the RRI as an earlier predictor of AKI has been studied in a wide range of clinical situations [12–15]. Platt and colleagues [16] showed that the RRI may distinguish acute tubular necrosis from prerenal failure. Distinguishing transient from persistent AKI remains clinically relevant as a way to implement and validate adequate therapeutic intervention [17, 18]. Nevertheless, to date there are few data on the role of RRI prediction of AKI in patients with acute TAAD. Because a shorter duration of AKI has been associated with improved long-term survival after cardiac surgical procedures [19], early diagnosis may allow physicians to apply appropriate treatment that could improve prognosis [20]. The objective of this study was to assess value of the RRI measured during perioperative periods in distinguishing transient from persistent AKI in patients after surgical repair of TAAD.
cute kidney injury (AKI) is associated with increased morbidity and mortality rates in patients after aortic surgical procedures [1]. With an incidence of 18% to 55%, AKI affects patients’ prognosis as well as long-term mortality rates, even in patients with partial and complete recovery [2]. Early diagnosis of AKI is difficult simply based on an increase in the level of conventional markers, such as serum creatinine (SCr) level or urinary output [3, 4]. These markers are delayed and unreliable, and they can be affected by several factors during the postoperative period [5]. Newer biomarkers of AKI, such as cystatin C and neutrophil gelatinase-associated lipocalin (NGAL), although more sensitive in earlier detection, have not yet been used routinely [6]. Especially when there is need to choose one or several biomarkers, the clinical relevance, thresholds of significance, and timing for measurement are all parameters to consider in different subsets of patients with AKI [7].
Accepted for publication March 27, 2017. Address correspondence to Dr Sun, Department of Cardiovascular Surgery, Beijing Anzhen Hospital, Capital Medical University, 2 Anzhen Rd, Beijing 100029 China; email: [email protected].
Ó 2017 by The Society of Thoracic Surgeons Published by Elsevier Inc.
(Ann Thorac Surg 2017;104:1583–9) Ó 2017 by The Society of Thoracic Surgeons
0003-4975/$36.00 http://dx.doi.org/10.1016/j.athoracsur.2017.03.057
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Can Renal Resistive Index Predict Acute Kidney Injury After Acute Type A Aortic Dissection Repair?
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Patients and Methods
Table 1. Classification of Acute Kidney Injury Network
The Ethics Committee of Beijing Anzhen Hospital approved this study and waived the need for individual informed consent.
Stage 1
Patients A prospective, observational study was conducted between April and July 2016 in patients with acute TAAD who underwent a total arch replacement and frozen elephant trunk implantation (TAR and FET). The surgical procedure was performed using deep hypothermic circulatory arrest and selective antegrade cerebral perfusion [21]. Inclusion criteria were acute TAAD in patients who were older than 18 years of age. Exclusion criteria were a history of preoperative renal replacement therapy, age younger than 18 years, pregnancy, or death occurring within 48 hours postoperatively.
Diagnostic Criteria for Postoperative Acute Kidney Injury A routine hospital immunoenzymatic method was used to measure SCr. An assessment of SCr value was made preoperatively and daily postoperatively. Postoperative AKI was diagnosed according to the criteria of the Acute Kidney Injury Network (AKIN) [22], which are shown in Table 1. The AKI criteria comprised the following: (1) an absolute increase in SCr of 0.3 mg/dL (26.4 mmol/L) or greater; (2) a percentage increase in SCr of 50% or greater; or (3) urine output less than 0.5 mL/kg/h for 6 hours or longer.
Study Protocol Demographic, intraoperative, and postoperative data were recorded prospectively. The RRI was measured on the day before the operation, immediately afterward, and at 6, 24, and 48 hours postoperatively. Recovery from AKI was defined as a 50% decrease in SCr or a return of SCr to its measured or estimated baseline level, or both [15, 23]. Transient AKI was defined as recovery from AKI within 3 postoperative days. Persistent AKI was defined as persistent elevation of SCr after 3 postoperative days.
Measurements of the Renal Resistive Index Doppler-based RRI measurement was obtained from a posterolateral approach [11, 24] by using a transparietal 5-MHz pulsed-wave Doppler probe (GE Vivid E9, Horten, Norway). The RRI was calculated using the following equation: RRI ¼
Peak systolic velocity – End diastolic velocity Peak systolic velocity
The best option for measuring the RRI is the arcuate arteries, and measurements were obtained using pulsewave Doppler imaging [25]. Two expert echocardiographers performed the examinations and served as controls for each other. The RRI was tested three times by two investigators in 10 patients preoperatively to evaluate interobserver variability (mean, 0.001; SD 0.013; p ¼ 0.811). The minimum and maximum Doppler shifts were
2 3
Serum Creatinine
Urine Output
Increase of 0.3 mg/dL (26.4 <0.5 mL/kg/h for >6 h mmol/L) or increase of 150%–200% (1.5- to 2-fold) from baseline Increase of>200%–300% (>2- <0.5 mL/kg/h for >12 h to 3-fold) from baseline Increase of >300% (>3-fold) <0.3 mL/kg/h for 24 h or anuria for 12 h from baseline (or value of l4.0 mg/dL[354 mmol/L] with an acute increase of >0.5 mg/dL [44 mmol/L]) or need for renal replacement therapy
recorded. A reading was considered satisfactory once three consecutive similar waveforms were obtained and the average of three measurements was taken. The RRI then was calculated as the average RRI for each kidney.
Statistical Analysis Data were analyzed with SPSS for Windows version 20.0 (IBM Corp, Armonk, NY). Continuous and categorical variables are expressed as mean SD (or median and range) and the number and percentage of patients, as appropriate. The c2 test was used to identify univariate predictors for AKI. Receiver-operating characteristic curves were constructed to assess the diagnostic value of the RRI. The optimal cutoff was first assessed by Youden’s index (J ¼ Sensitivity þ Specificity 1). Linear regression analysis was used to assess the correlation between the maximum levels of RRI (RRImax) and SCr. All analyses were two-sided, and any p value of <0.05 was considered statistically significant.
Results Among the 73 patients undergoing TAR and FET for repair of acute TAAD during the study period, 11 patients were excluded (1 for arrhythmia, 2 because they died during the first 48 hours postoperatively, 7 for incomplete data, 1 for pregnancy), and 62 patients were included in this study, as shown in Figure 1. Among the 62 patients, 22 (35.5%) patients presented with no AKI, transient AKI developed in 21 (33.9%), and 19 (30.6%) had persistent AKI, 12 of whom required dialysis. Patients’ characteristics were similar among patients with no AKI, transient AKI, and persistent AKI, except for the SCr (p ¼ 0.037) before operation (Table 2). Thirteen of 19 patients with persistent AKI had neurologic complications, and spinal cord injury occurred in 1 patient (1.6%; 1 of 62). Five patients with persistent AKI died within 30 days after the surgical procedure. The postoperative rates of neurologic complications and mortality were significantly different between patents with persistent AKI and patients with transient and no AKI (p < 0.001 and p ¼ 0.001, respectively) (Table 2). The RRImax differed significantly among patients with no AKI,
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p < 0.001). Continuous renal replacement therapy was eventually required in 12 of 19 patients with persistent AKI compared with the 43 other patients (p < 0.001). The areas under the receiver-operating characteristic curve (AUC) of preoperative SCr was 0.659 (95% confidence interval, 0.510 to 0.809; p ¼ 0.047). The AUC of RRImax was 0.918 (95% confidence interval, 0.850 to 0.986; p < 0.001). The AUC of RRImax showed a higher value to predict persistent AKI (p < 0.001) (Fig 2). RRImax had a sensitivity of 94.7% and a specificity of 72.1%. The cutoff of RRImax for diagnosing persistent AKI was 0.725.
Fig 1. Flow chart of the study. (AKI ¼ acute kidney injury; postop ¼ postoperative; TAAD ¼ type A aortic dissection; TAR þ FET ¼ total arch replacement and frozen elephant trunk implantation.)
transient AKI, and persistent AKI (0.67, 0.71, 0.78, respectively; p < 0.001). The level of preoperative RRI did not differ among the groups with no AKI, persistent AKI, and persistent AKI. However, the level of RRI significantly increased in patients with postoperative AKI compared with patients without AKI (p < 0.001). Linear regression analysis detected a significantly positive correlation between RRImax and SCr during 2 days postoperatively (rho ¼ 0.606;
Correlation of Kidney Perfusion with Development of Acute Kidney Injury Preoperative computed tomography scans showed that the dissection extended to the suprarenal abdominal aorta in 17.7% (11 of 62) and the iliac artery in 82.3% (51 of 62), a finding that did not differ among three groups (p ¼ 0.816). Bilateral kidney perfusion from the true lumen was observed in 63.6% (14 of 22), 52.4% (11 of 21), and 47.4% (9 of 19), and unilateral kidney perfusion from the true lumen was noted in 36.4% (8 of 22), 47.6% (10 of 21), and 52.6% (10 of 19) of patients with no AKI, transient AKI, and persistent AKI, respectively (Table 3). Perfusion of both kidneys from the false lumen was not observed in the cohort. However, in a 57-year-old man with an aortic
Table 2. Preoperative, Operative, and Postoperative Data Variable Demographic data Male Age (y) Body mass index (kg/m2) Medical history Hypertension Diabetes Marfan syndrome Cerebrovascular disease COPD Smoking Preoperative SCr (mmol/L) Preoperative RRI Operative data CPB time (min) Cross-clamp time (min) DHCA time (min) RBC use (unit) Postoperative results Postoperative RRImax CRRT Neurologic complications Reexploration for bleeding Operative mortality
Total (N ¼ 62) (%)
No AKI (n ¼ 22) (%)
Transient AKI (n ¼ 21) (%)
Persistent AKI (n ¼ 19) (%)
51 (82.3) 47.3 11.3 26.2 3.5
19 (86.4) 43.1 10.1 25.3 3.2
17 (81.0) 47.9 11.2 26.6 3.5
15 (78.9) 51.5 11.5 26.5 3.8
0.818 0.055 0.399
17 1 2 1
p Value
45 (72.6) 2 (3.2) 4 (6.5) 3 (4.8) 2 (3.2) 29 (46.8) 90.7 43.5 0.65 0.05
(77.3) (4.5) (9.1) (4.5) 0 10 (45.5) 84.1 23.8 0.63 0.04
15 (71.4) 1 (4.8) 1 (4.8) 0 2 (9.5) 11 (52.4) 78.7 22.3 0.65 0.04
13 (68.4) 0 1 (5.3) 2 (10.5) 0 8 (42.1) 111.5 67.2 0.66 0.07
0.399 0.645 0.827 0.311 0.137 0.808 0.037 0.063
233.8 51.1 137.5 33.9 23.7 8.1 5.6 4.1
219 35 129 30 27 10 4.9 4.2
241 59 142 36 26 7 5.1 4.3
241 56 141 36 21 6 6.8 3.7
0.271 0.402 0.078 0.261
0.72 0.06 12 (19.4) 20 (32.3) 4 (6.5) 5 (8.1)
0.67 0.03 0 3 (13.6) 0 0
0.71 0.05 0 4 (19.0) 3 (14.3) 0
0.78 0.05 12 (63.2) 13 (68.4) 1 (5.3) 5 (26.3)
<0.001 <0.001 <0.001 0.163 0.001
AKI ¼ acute kidney injury; COPD ¼, chronic obstructive pulmonary disease; CPB ¼ cardiopulmonary bypass; CRRT ¼ continuous renal replacement therapy; DHCA ¼ deep hypothermic circulatory arrest; RBC ¼ red blood cell; RRI ¼ renal resistive index; SCr ¼ serum creatinine.
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patients and 3 survivors in the persistent AKI group) showed that perfusion of the kidneys at 3 months did not change compared with preoperative findings (Table 3).
Comment The main finding of our study was the ability of postoperative RRImax to predict persistent AKI with a high level of sensitivity (94.7%) and specificity (72.1%) at an early stage after repair of acute TAAD. This finding implies that Doppler-based RRI may be a promising tool in assessing chances for renal recovery. Brown and colleagues [26] demonstrated a direct correlation between duration of AKI and long-term mortality rates. Early recovery of renal function after cardiac surgical procedures has been shown to improve long-term survival [19]. Measurement of renal velocity by Doppler ultrasound is a noninvasive and rapid surrogate method that allows the instantaneous assessment of parenchymal renal perfusion [24, 27], as well as the differentiation of transient from persistent AKI. Darmon and associates [15] showed that an elevated RRI greater than 0.795 predicted persistent AKI with 82% sensitivity and 92% specificity in critically patients who required mechanical ventilation. A meta-analysis by Ninet and associates [28] also showed that an elevated RRI was associated with the reversibility of AKI in critically ill patients with severe sepsis, cardiac surgical procedures, mechanical ventilation, or diagnosed AKI. Differentiating persistent AKI from transient AKI may be helpful in treatment decision making. However, the role of the RRI in the shortterm therapeutic regimen of AKI has to await further validation in larger series, especially in patients undergoing other cardiac surgical operations. Early intervention for AKI is definitely associated with lower costs, shorter hospital stays, and better outcomes. In this study, the incidence of persistent AKI was 30.6%, and 19.4% of patients required dialysis. These results are similar to the overall incidence found in our department in patients undergoing repair of acute TAAD [29]. After acute aortic dissection, the mechanisms of AKI mainly
Fig 2. Receiver-operating characteristic of serum creatinine before the operation and maximum renal resistive index (RRImax, the maximum renal resistive index measured at different time points: immediately after the surgical procedure and at 6, 24, and 48 postoperative hours). (AUC ¼ areas under receiver-operating characteristic curve; pre-SCr ¼ preoperative serum creatinine.)
arch entry tear, the left kidney was perfused from the true lumen, whereas the right kidney was perfused from both the true and false lumina. The perfusion of both kidneys remained unchanged postoperatively in this patient (Fig 3). Although perfusion from the true lumen did not differ among the three groups (p ¼ 0.558), one-kidney perfusion from the true lumen was found to be associated with a significantly higher mortality rate for the entire cohort (5 of 30 vs 0 of 32; p ¼ 0.022) and for patients with persistent AKI (5 of 10 vs 0 of 9; p ¼ 0.033). Follow-up computed tomography scans, available in 54 patients (excluding 5 deceased Table 3. Extension of Dissection and Kidney Perfusion Variable Extension of dissection Suprarenal abdominal aorta Iliac artery Perfusion of kidney Preoperative CTA One kidney from true lumen Both kidneys from true lumen Postoperative CTA One kidney from true lumen Both kidneys from true lumen
Total (N ¼ 62) (%)
No AKI (n ¼ 22) (%)
Transient AKI (n ¼ 21) (%)
Persistent AKI (n ¼ 19) (%)
11 (17.7) 51 (82.3)
3 (13.6) 19 (86.4)
4 (19.0) 17 (81.0)
4 (21.1) 15 (78.9)
28 (45.2) 34 (54.8) (n ¼ 54) 20 (37.0) 34 (63.0)
8 (36.4) 14 (63.6) (n ¼ 22) 8 (36.4) 14 (63.6)
10 (47.6) 11 (52.4) (n ¼ 21) 10 (47.6) 11 (52.4)
10 (52.6) 9 (42.1)a (n ¼ 11)b 2 (18.2) 9 (81.8)
p Value 0.816
0.558
0.261
a b In 1 patient, the right kidney was perfused from both the true and false lumina (Fig 3). Five patients died postoperatively, and 3 of 14 survivors did not have follow-up CTA scans; at 3 months, CTA scan was available in only 11 patients with persistent AKI.
AKI ¼ acute kidney injury;
CTA ¼ computed tomographic angiogram.
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Fig 3. Computed tomography in a patient with arch entry tear, (A) the right kidney was perfused from both the true and false lumina, whereas (B) the left kidney was perfused from the true lumen. (C, D) The perfusion of both kidneys remained unchanged at 3 months after ascending aortic and total arch replacement with frozen elephant trunk implantation.
include two categories: prerenal or intrinsic [5]. Prerenal AKI resulting from decreased renal perfusion is reversible. There is a pathophysiologic continuum from transient AKI to persistent AKI, so prompt recognition and rapid restoration of renal perfusion may prevent or attenuate acute tubular necrosis [30]. In patients with persistent AKI, avoiding potentially deleterious interventions and promptly starting renal replacement therapy may improve outcomes [15, 31, 32]. Our RRI threshold of 0.725 for predicting persistent AKI after repair of acute TAAD is similar to that found in human septic shock and approaches the predictive values (RRI >0.70) reported in humans and in a rabbit model of AKI. Guinot and colleagues [20] reported that an RRI threshold value greater than 0.73 can distinguish transient from persistent AKI after cardiac surgical procedures. Indeed, the RRI is used for assessing instant renal perfusion, which only subsequently leads to accumulation
of SCr and reduced urine output [33]. Routine evaluation of the RRI in patients at risk for AKI could encourage clinicians to maximize renal-sparing measures such as reestablishment of renal perfusion and initiation of preventive therapies to attenuate acute tubular necrosis [15]. Moreover, the RRI is correlated with the severity of renal dysfunction. Such a prompt response to AKI would not be possible if the therapeutic strategy is based on delayed criteria, such as the increase in SCr or sustained oliguria. Therefore the development of a marker allowing for early detection of AKI may help clinicians prevent persistent AKI in patients with transient AKI [17]. In this study, the levels of preoperative RRI were similar in patients who subsequently developed AKI and in those without postoperative AKI. A lack of correlation between RRI and SCr before kidney injury was previously noted in patients with septic shock [14]. This finding suggests that the RRI is a distinct marker of AKI,
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rather than a reflection of preexisting chronic renal insufficiency. Beyond its ability to predict the reversibility of AKI, the RRI has several advantages: rapidity, portability, realtime imaging, high feasibility, simplicity, ease of use, and capability of repeated assessments [34]. Thus the RRI may become a useful tool for adjusting management decisions based on the severity of AKI at the bedside by providing information about renal perfusion [20].
Study Limitations The sample size was relatively small in this single-center experience. The average age of patients was much younger compared with Western series, and all patients underwent TAAD repair with the FET technique; patients undergoing other aortic procedures such as isolated total arch replacement (without an FET) were not included. Nor were long-term data on morbidity or mortality available in this cohort. The RRI depends on several interrelated parameters (vascular resistance and heart rate). Indeed, increased vascular resistance and decreased heart rate were shown to raise the RRI. Some studies indicated that the RRI could be influenced by mean arterial pressure [14], vascular compliance, pulse pressure [35, 36], oxygen level [37], or intraabdominal pressure [38]. These factors were not taken into consideration in our study. We purposely excluded patients with arrhythmia from this study. Thus we assume that the dependence of RRI on heart rate was sufficiently controlled to limit the bias in the RRI assessment. Additional prospective studies are warranted to assess potential confounders more accurately. Despite the vagaries of the RRI measurement and its possible inaccuracies related to hemodynamic issues, RRI may be helpful in detecting and treating AKI earlier and be included among the postoperative diagnostic techniques to improve patients’ outcomes. AKI after major cardiac and thoracic aortic operations is one of the most difficult complications to avoid. Future studies will allow for identifying patients with impending AKI earlier, intervening on time, and then hopefully decreasing the rate of AKI.
Conclusions This study showed that the RRImax during the first 48 postoperative hours could predict persistent AKI after surgical repair of acute TAAD with good sensitivity and specificity. Determination of RRI with Doppler sonography is feasible and may be helpful in the diagnosis of persistent AKI.
This study was supported in part by the National Key Technologies Research and Development Program (Grant 2015BA112B03) and Special Research Fund for Public Health and Welfare (Grant 201402009).
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