- Email: [email protected]
Risk Index for Postoperative Acute Kidney Injury After Valvular Surgery Using Cardiopulmonary Bypass
Risk Index for Postoperative Acute Kidney Injury After Valvular Surgery Using Cardiopulmonary Bypass Takashi Yamauchi, MD, PhD, Shigeru Miyagawa, MD, PhD, Yasushi Yoshikawa, MD, PhD, Koichi Toda, MD, PhD, and Yoshiki Sawa, MD, PhD, for the Osaka Cardiovascular Surgery Research (OSCAR) Group* Department of Cardiovascular Surgery, Osaka General Hospital, Osaka City, Osaka; and Department of Cardiovascular Surgery, Osaka University Graduate School of Medicine, Suita, Osaka, Japan
Background. Acute kidney injury (AKI) after valvular surgical procedures with cardiopulmonary bypass carries potentially high mortality and morbidity rates. This study investigated the risk factors for AKI, and the study investigators developed a risk index to predict postoperative AKI. Methods. A total of 1,484 consecutive non–dialysisdependent patients who underwent valvular operations using cardiopulmonary bypass between 2008 and 2011 were retrospectively investigated. The definition of AKI is newly required temporary hemodialysis or a creatinine level greater than 2.0 mg/dL with more than twofold elevation compared with the preoperative value. Results. Postoperative AKI occurred in 91 patients (6.1%), among whom new dialysis dependence occurred in 45 patients (3.1%), resulting in hospital death in 22 patients (48.9%), discharge with renal function recovery in 19 (42.2%), and permanent dialysis dependence in 4 (8.9%). The overall hospital mortality rate was 3.9%. The mortality rate in patients with postoperative AKI-related
complications and those who required new hemodialysis was 35.2% (32 of 91) and 48.9% (22 of 45), respectively, which was higher than in patients without AKI (1.9%; 26 of 1,393). Independent risk factors of postoperative AKI were smoking (odds ratio [OR], 2.008; p [ 0.0151), diabetes mellitus (OR, 2.730; p [ 0.0014), arteriosclerosis obliterans (OR, 4.351; p [ 0.0317), congestive heart failure (OR, 2.455; p [ 0.0052), estimated glomerular filtration rate less than or equal to 30 mL/min (OR, 4.855; p < 0.0001), and operation time longer than 8 hours (OR, 4.068; p [ 0.0005). The risk index based on these risk factors predicted postoperative AKI (area under the curve, 0.81) and new requirement of hemodialysis (area under the curve, 0.86). Conclusions. Based on these risk factors, the study investigators were able to predict the postoperative incidence of renal dysfunction after valvular operations with cardiopulmonary bypass.
P
ostoperative acute kidney injury (AKI) is a serious complication of cardiac surgical procedures that carries a high mortality rate [1, 2]. In various studies reporting the incidence of and risk factors for postoperative AKI after cardiac operations, cardiopulmonary bypass (CPB) has been established as a risk factor for postoperative renal impairment [1, 3–9]. In coronary artery bypass surgery, off-pump coronary artery bypass grafting has been reported to reduce postoperative AKI [10]. In the field of valvular surgery, most operations still require CPB, although transcatheter aortic valve implantation [11] and placement of a mitral clip [12], which can be performed off-pump, have been increasingly
promoted as alternative techniques. In clinical settings, non–dialysis-dependent patients with preexisting severe renal failure sometimes hesitate to undergo cardiac operations to avoid transition to permanent hemodialysis. However, the incidence of such transition postoperatively remains unclear. In the present study, we investigated the risk factors for AKI and the incidence of transition to permanent dialysis after valvular operations using CPB. The relationship between a risk index based on identified risk factors and the postoperative incidence of AKI was also investigated in hopes of improving clinical outcomes in this population.
Accepted for publication Feb 6, 2017.
Patients and Methods
*A complete list of the facilities affiliated with the Osaka Cardiovascular Surgery Research Group (OSCAR) appears at the end of this article.
Patients
Address correspondence to Dr Sawa, Department of Cardiovascular Surgery, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan; email: [email protected].
Between 2008 and 2011, 1,484 consecutive valvular surgical procedures (with and without concomitant operations) performed at Osaka University (Osaka, Japan) and
Ó 2017 by The Society of Thoracic Surgeons Published by Elsevier Inc.
(Ann Thorac Surg 2017;-:-–-) Ó 2017 by The Society of Thoracic Surgeons
0003-4975/$36.00 http://dx.doi.org/10.1016/j.athoracsur.2017.02.012
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its 22 associated facilities (Osaka Cardiovascular Surgery Research Group [OSCAR]) whose medical information was registered in the Japan Adult Cardiovascular Surgery Database (JACVSD) were retrospectively reviewed.
Definition The definitions of data in the present study coincide with those of the JACVSD, most of which are identical to those in The Society of Thoracic Surgeons National Database (available online at http://sts.org). The JACVSD definitions are also available online (http://www.jacvsd.umin. jp). The definition of AKI is new requirement of hemodialysis or a creatinine (Cr) level greater than 2.0 mg/dL with a more than twofold elevation compared with the preoperative value. Renal function is assessed by calculating the glomerular filtration rate (GFR) using revised equations for estimated GFR (eGFR) from serum creatinine for Japan, as follows: GFR ¼ 194 (Cr, mg/dL) 1.094 (age) 0.287 0.739 (if female) [13].
Statistical Analysis Values of variables are expressed as mean standard deviation or as percentages. Methods of univariate analysis included Student’s t test for continuous variables and the c2 test or Fisher’s exact test for categorical variables. Significant variables from the univariate analysis (p < 0.2) were subjected to multivariate analysis using the Cox binary logistic regression model. Statistical significance was assumed for a p value of less than 0.05. To assess the ability of significant variables from the multivariate analysis, the odds ratio (OR) was calculated. The validity of the risk index was examined using a receiver-operating characteristic (ROC) curve. Statistical analyses were performed using JMP 8.0 software (SAS Institute, Cary, NC).
Results Patients’ Characteristics Patients’ characteristics are listed in Table 1. The mean age was 69.3 12.5 years, and 52% of the patients were male. All patients were non–dialysis dependent. The percentage of patients with an eGFR of 30 mL/min or less was 11.4%, those with an eGFR between 30 and 60 mL/ min was 42.0%, and those with an eGFR of 60 mL/min or greater was 46.6%. Mean ejection fraction was 60.7% 14.7%. Congestive heart failure was observed in 328 patients (22.1%). Elective operations were performed in 1,399 patients (94.3%). Combined aortic surgical procedures and coronary artery bypass grafting were performed in 92 (6.2%) and 216 (14.6%) patients, respectively. Aortic valve replacement was performed in 785 patients (52.9%), mitral valve replacement in 331 (22.3%), and mitral reconstructive operations in 461 (31.1%). Mean operation time was 351 149.7 minutes, and the mean CPB time was 124.1 45.8 minutes. The postoperative hospital stay 28.4 26.3 days in the group without AKI and 45.7 34.9 days in the group with AKI (p < 0.001). The overall hospital mortality rate was 3.9% (Table 1).
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Incidence of Postoperative Acute Kidney Injury and Requirement of New Hemodialysis The incidence of postoperative AKI and new hemodialysis requirement is listed in Figure 1. Postoperative AKI occurred in 91 patients (6.1%), 45 of whom (3.1%) were newly dependent on dialysis, resulting in hospital death in 22 patients (48.9%), discharge with recovery of renal function in 19 (42.2%), and permanent dialysis dependence in 4 (8.9%). The incidence of AKI stratified according to GFR (GFR 30 mL/min, 30 to 60 mL/min, and 60 mL/min) was 20.7%. 5.8%, and 2.9%, respectively. Postoperative requirement for new dialysis in these patients was 14.8%, 2.2%, and 0.9%, respectively. The mortality rate related to postoperative AKI and new requirement of hemodialysis was 35.2% (32 of 91) and 48.9% (22 of 45), respectively, considerably higher than in patients without AKI (1.9%; 26 of 1,393).
Risk Factor Analysis Multivariate analysis of postoperative AKI (Table 2) showed that independent risk factors were smoking history (OR, 2.008; 95% confidence interval (CI), 1.144 to 3.524; p ¼ 0.0151), diabetes mellitus (DM) (OR, 2.730; 95% CI, 1.472 to 5.063; p ¼ 0.0014), arteriosclerosis obliterans (ASO) (OR, 4.351; 95% CI, 1.138 to 10.641; p ¼ 0.0317), congestive heart failure (OR, 2.455; 95% CI, 1.307 to 4.612; p ¼ 0.0052), eGFR of 30 mL/min or less (OR, 4.855; 95% CI, 2.599 to 9.068; p < 0.0001), and operation time longer than 8 hours (OR, 4.068; 95% CI, 1.842 to 8.982; p ¼ 0.0005).
Risk Index Development Based on the risk factor analysis, we developed a risk index for prediction of the incidence of postoperative AKI. To develop relative weights for the predictors in the renal risk index, we rounded the OR in the final multiple logistic model to the nearest integer. According to magnitude of the OR in the multivariate analysis, we weighed the factors as follows: smoking, 2 points; ASO, 4 points; DM, 2 points; heart failure, 2 points; eGFR of 30 mL/min or less, 5 points; operation time longer than 8 hours, 4 points.
Risk Index Including Preoperative and Intraoperative Risk Factors To investigate the validity of this risk index when including preoperative and intraoperative risk factors, we used all risk factors (ranging from 0 to 19 points), and the final model was evaluated using the area under the ROC curve (AUC), which represents the predictive ability. The AUC of postoperative AKI and new requirement of hemodialysis was 0.81 and 0.86, respectively (Fig 2A). The cohort was divided into three categories: low risk (score, 0 to 2: 871 patients), medium risk (score, 3 to 7: 480 patients), and high risk (score 8: 133 patients). The incidence of postoperative AKI in low-, medium-, and high-risk categories was 1.8%, 7.5%, and 28.8%, respectively (Fig 2B). The incidence of postoperative new requirement of dialysis in low-, medium-, and high-risk categories was 0.6%, 4.0%, and 15.9%, respectively (Fig 2B).
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Table 1. Patients’ Characteristics Characteristics Age Sex (male) Body surface area (m2) Smoking Diabetes mellitus Hypertension Hyperlipidemia Preoperative creatinine eGFR eGFR <30 30< eGFR <60 eGFR 60 Infectious endocarditis (active þ chronic) Infectious endocarditis (active) Chronic obstructive pulmonary disease Arteriosclerosis obliterans Carotid stenosis Liver dysfunction Cardiac condition Heart failure NYHA N/A I II III IV No. of diseased coronary vessels None One Two Three LV function (ejection fraction) Surgical procedure Single valve surgery Multivalve surgery Aortic valve surgery Replacement Root reconstruction valve conduit Repair or reconstruction Reconstruction with valve sparing Mitral valve surgery Replacement Annuloplasty only Reconstruction with annuloplasty Reconstruction without annuloplasty Valvectomy Tricuspid valve surgery Annuloplasty only Replacement Reconstruction with annuloplasty Valvectomy
All Cases (n ¼ 1,484)
AKI (n ¼ 91)
non-AKI (n ¼ 1,394)
p Value Second
69.3 12.5 772 (52.0%) 1.54 0.2 475 (32.0%) 297 (20.0%) 859 (57.9%) 443 (29.9%) 0.97 0.66
72.3 10.9 54 (59.3) 1.58 0.2 41 (45.1) 39 (42.9) 61 (67.0) 33 (36.3) 1.56 0.92
69.1 12.5 718 (51.5) 1.54 0.2 434 (31.1) 258 (18.5) 798 (57.2) 410 (29.4) 0.94 0.62
<0.001 NS NS 0.006 <0.001 NS NS <0.001
169 623 692 124 92 130 92 58 45
(11.4%) (42.0%) (46.6%) (8.4%) (6.2%) (8.7%) (6.2%) (3.9%) (3.0%)
35 36 20 15 14 8 16 10 7
(38.5) (39.6) (22.0) (16.5) (15.4) (8.8) (17.6) (11.0) (7.7)
134 587 672 109 78 122 76 48 38
(9.6) (42.1) (48.2) (7.8) (5.6) (8.8) (5.5) (3.4) (2.7)
<0.001 . . <0.001 <0.001 NS <0.001 <0.001 0.008 <0.001
328 (22.1%)
39 (42.9)
289 (20.7)
60 248 737 354 85
2 13 39 24 13
58 235 698 330 72
(4.0%) (16.7%) (49.7%) (23.9%) (5.7%)
(2.2) (14.3) (42.9) (26.4) (14.3)
(4.2) (16.9) (50.1) (23.7) (5.2)
0.017
0.004 . . . 0.002
926 (75.2%) 150 (12.2%) 71 (5.8%) 82 (6.7%) 60.7 14.7
43 (47.3) 11 (12.1) 10 (11.0) 8 (8.8) 55.9 17.3
883 (63.3) 139 (10.0) 61 (4.4) 74 (5.3) 61.1 14.1
886 (59.7%) 598 (40.3%)
52 39
834 559
NS .
785 34 10 4
(52.9%) (2.3%) (0.7%) (0.3%)
44 6 1 1
(48.4) (6.6) (1.1) (1.1)
741 28 9 3
(53.2) (2.0) (0.6) (0.2)
0.013
331 196 265 20 2
(22.3%) (13.2%) (17.9%) (1.3%) (0.1%)
26 14 14 1 0
(28.6) (15.4) (15.4) (1.1) (0.0)
305 182 251 19 2
(21.9) (13.1) (18.0) (1.4) (0.1)
0.013 . . . .
480 9 6 1
(32.3%) (0.6%) (0.4%) (0.1%)
25 1 2 1
(27.5) (1.1) (2.2) (1.1)
455 8 4 0
(32.6) (0.6) (0.3) (0.0)
0.003 . . .
. .
(Continued)
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Table 1. Continued Characteristics Pulmonary valve surgery Replacement Concomitant surgery Thoracic surgery Coronary artery bypass grafting Arrhythmia surgery Urgency Elective Urgent Emergency Salvage Transfusion Operation time (min) Cross-clamp time (min) Lowest temperature during CPB <30 C Circulatory arrest Perfusion time (min) Postoperative course Postoperative mechanical circulatory support Hospital stay after surgery (days) Dead Status at discharge Not affected (modified Rankin scale grade 0–3) Moderately affected (modified Rankin scale grade 4) Severely affected (modified Rankin scale grade 5)
All Cases (n ¼ 1,484)
AKI (n ¼ 91)
non-AKI (n ¼ 1,394)
8 (0.6%)
0 (0.0)
8 (0.6)
92 (6.2%) 216 (14.6%) 338 (22.8%)
9 (9.9) 22 (24.2) 15 (16.5)
83 (6.0) 194 (13.9) 323 (23.2)
p Value Second
NS 0.017 . .
1,399 (94.3%) 42 (2.8%) 42 (2.8%) 1 (0.1%) 1,241 (83.6%) 351.2 149.7 124.1 45.8 196 (13.2) 21 (1.4) 177.2 63.4
78 (85.7) 7 (7.7) 6 (6.6) 0 (0.0) 87 (95.6) 456.4 165.3 147.6 57.9 19 (20.9) 2 (2.1) 222.1 88.5
1,321 (94.8) 35 (2.5) 36 (2.6) 1 (0.1) 1,154 (82.8) 344.3 146.1 122.6 44.6 177 (12.7) 19 (1.3) 174.2 60.2
0.004 . . . 0.001 <0.001 <0.001 0.026 NS <0.001
12 (0.8) 28.6 32.5 58 (3.9%)
7 (7.7) 45.7 34.9 32 (35.2)
5 (0.4) 28.4 26.3 26 (1.9)
<0.001 <0.001 <0.001
1,353 (91.2%) 56 (3.9%) 17 (1.2%)
49 (53.8) 8 (8.8) 2 (2.2)
AKI ¼ acute kidney injury; CPB ¼ cardiopulmonary bypass; eGFR ¼ estimated glomerular filtration rate; not applicable; NS ¼ not significant; NYHA ¼ New York Heart Association (functional class).
Risk Index Including Preoperative Risk Factors To investigate the validity of this risk index when including preoperative risk factors, we used all risk factors (ranging from 0 to 15 points), and the final model was evaluated using the AUC to represent predictive ability. The AUC of postoperative AKI and new requirement of hemodialysis was 0.77 and 0.82, respectively (Fig 3A). The cohort was once again divided into the three categories: low risk (score, 0 to 2: 964 patients), medium risk (score, 3 to 6: 367 patients), and high risk (score 7: 153 patients). The incidence of postoperative AKI for low-, medium-, and high-risk categories was 2.7%, 7.4%, and 28.8%, respectively (Fig 3B). The incidence of postoperative new requirement of dialysis for low-, medium-, and high-risk patients was 1.1%, 3.3%, and 15.0%, respectively (Fig 3B). The relationships among operation time, incidence of postoperative AKI, and new requirement of hemodialysis stratified by the risk scores are listed in Figure 4. Regarding postoperative AKI, in patients whose operation time was within 5 hours, the incidence in the low-, medium-, and high-risk groups was 0.7%, 2.7%, and 9.5%; in patients whose operation time was from 5 to 8 hours, the incidence was 2.8%, 7.6%, and 27.1%; and for those whose operation time was longer than 8 hours, the incidence was 10.8%, 18.0%, and 40.0%, respectively. With respect to postoperative new requirement of
1,304 (93.5) 48 (3.4) 15 (1.1)
<0.001 . .
LV ¼ left ventricular;
N/A ¼
hemodialysis, the incidence in low-, medium-, and highrisk groups, respectively, was as follows: operation time within 5 hours, 0.2%, 0.7%, and 7.1%; operation time from 5 to 8 hours, 0.9%, 3.2%, and 17.2%; and operation time longer than 8 hours, 6.5%, 11.4%, and 20.0%.
Comment Among morbidities after cardiac surgical procedures, AKI greatly worsens the patient’s prognosis. Although various studies have been reported regarding the risk model of AKI after open heart surgery, most are concerned with outcomes of coronary artery bypass grafting and aortic or pediatric surgery, rather than focusing on valvular surgery [4, 14–18]. In an aging society, valvular surgical procedures have been increasing and are also undergoing drastic changes in response to the advent of transcatheter surgical procedures such as transcatheter aortic valve implantation and the mitral clip. Many earlier reports have shown the predicted incidence of AKI after operations using CPB stratified by each risk score, as displayed in Figures 2 and 3 in the present study. However, few studies have shown the relationship between the incidence of AKI and operation time stratified by the risk score as displayed in Figure 4, which shows that the incidence of AKI in patients classified even at the same
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Fig 1. Incidence of postoperative renal dysfunction. (AKI ¼ acute kidney injury; CPB ¼ cardiopulmonary bypass; eGFR ¼ estimated glomerular filtration rate; HD ¼ hemodialysis; Pts ¼ patients.)
risk score increases in proportion to the operation time. We believe that this result may contribute to the selection of surgical procedure, especially in cases of valvular surgical procedures requiring other concomitant operations such as coronary artery and arrhythmia correction procedures. Various studies on the incidence of and risk factors for postoperative AKI after cardiac surgical procedures, according to each article’s definition, have been published
[19]. In the present study we determined five preoperative risk factors (preexisting renal dysfunction, smoking, ASO, DM, heart failure) and one intraoperative risk factor (prolonged operation time). Apart from our findings reported herein, longer duration of CPB, intraoperative hemodynamic instability (eg, multiple inotrope use, support of intraaortic balloon pumping, hypotension), and transfusion (eg, red blood cells, platelets, fresh frozen plasma) have been reported as risk factors for postoperative AKI
Table 2. Univariate and Multivariate Analysis of Postoperative Acute Kidney Injury Factors Preoperative factors Age 70 y Smoking Diabetes mellitus With insulin Infective endocarditis Active Arteriosclerosis obliterans Liver dysfunction Cardiovascular operative history Heart failure NYHA (III) Coronary artery disease (2 vessel) Poor LV function Emergency or urgent operation eGFR 30 Intraoperative factors CABG Lowest body temperature >30 Perfusion time >5 h Operative time >8 h AKI ¼ acute kidney injury; rate; LV ¼ left ventricular;
Univariate p Value
Multivariate p Value
Odds Ratio (95% CI)
Risk Scores
0.0404 0.0059 <0.0001 <0.0001 0.0038 0.0002 <0.0001 0.0075 0.0006 <0.0001 0.0019 0.0009 0.0019 0.0003 <0.0001
NS 0.0151 0.0014 NS NS NS 0.0317 NS NS 0.0052 NS NS NS NS <0.0001
. 2.008 (1.1443.524) 2.730 (1.4725.063) . . . 4.351 (1.13810.641) . . 2.455 (1.3074.612) . . . . 4.855 (2.5999.068)
. 2 3 . . . 4 . . 2 . . . . 5
. . . 4.068 (1.8428.982)
. . . 4
0.0072 0.00053 <0.0001 <0.0001
NS NS NS 0.0005
CABG ¼ coronary artery bypass grafting; CI ¼ confidence interval; eGFR ¼ estimated glomerular filtration NS ¼ not significant; NYHA ¼ New York Heart Association (functional class).
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Fig 2. Receiver-operator characteristic curve for postoperative renal dysfunction and incidence of acute kidney injury (AKI) and new hemodialysis (HD) including preoperative and intraoperative risk predictors. (AUC ¼ area under the curve.)
after cardiac operations [19]. Similar to previous analyses assessing risk, preexisting renal damage is an important predictor of renal events for well-defined reasons. Smoking history, ASO, and DM, well known as risk factors for atherosclerosis, may also be speculated as having adverse effects on the renal artery and its function. Among the other predictors, congestive heart failure is consistent with previous studies indicating the untoward effect of reduced renal perfusion [20]. In addition, prolonged operation time is identified as an intraoperative predictor, probably because of the magnitude of the inflammatory response in the kidney. As already mentioned, CPB time is a well-established independent risk factor for postoperative AKI. In the present study, CPB time was significant in univariate but not multivariate analysis (Table 2). Although CPB time is certainly crucial in affecting postoperative renal dysfunction, we believe that longer operation time may be a stronger predictor because the extended duration means that the operation requires both longer CPB time and a longer time for hemostasis, which require increased transfusion and lead to deterioration of postoperative renal function. Fig 3. Receiver-operator characteristic curve for postoperative renal dysfunction and incidence of acute kidney injury (AKI) and new hemodialysis (HD) including preoperative risk predictors. (AUC ¼ area under the curve.)
We also investigated the relationship between the incidence of postoperative AKI and the requirement for new hemodialysis, stratified according to the risk index including preoperative risk factors. In patients with low and medium risk (score, 0 to 6), the incidence of renal dysfunction is relatively low within 8 hours, but it increases drastically after 8 hours. In patients with a high risk score (7), the incidence rises to higher levels after more than 300 minutes of operative time. Therefore a shorter operation is desirable, especially in patients with a high risk score. The incidence of AKI necessitating dialysis after cardiac operations is relatively low (1% to 5%) [21–24]. Approximately 50% of patients with postoperative AKI in the present study required temporary or permanent hemodialysis, although the incidence of transition to permanent hemodialysis reported in the literature to date has been uncertain. In the present study, half of the patients requiring postoperative new hemodialysis died while in hospital, and approximately 20% of survivors transitioned to permanent hemodialysis (4 of 1,484: 0.4% overall). The fate of the patients newly requiring
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Fig 4. Relationship between operation time and postoperative renal dysfunction stratified by risk index including preoperative risk factors. (AKI ¼ acute kidney injury; HD ¼ hemodialysis.)
hemodialysis as reported in the historical literature once seemed catastrophic. The benchmark reports conducted by Chertow and colleagues [25] reported a mortality rate of 63% at 30 days for those patients requiring hemodialysis compared with 4.3% for patients without renal dysfunction. A slightly more recent report by Mangano and associates [20] identified similar mortality rates among patients with postoperative renal failure. The hospital stay appears longer than that in the Western world. The longer stays in hospital could be attributed to the fact that for patients in Japan, most medical costs are covered by national health insurance. There has been little progress in recent years in reducing the incidence of AKI, improving the prognosis of affected patients, or identifying it earlier in its pathologic course [2, 3, 26]. More recently published data suggest that perioperative blood pressure lability influences both the risk of postoperative renal dysfunction and 30-day mortality rates [19]. The present study reveals congestive heart failure as one of the preoperative risk factors. Therefore, if the possibility of medical treatment exists, surgical intervention after optimized heart failure may be more desirable from the perspective of prevention of renal function impairment. Medical management in the perioperative period has been reported to exert a beneficially protective effect on the kidney. Sezai and colleagues [27] reported that continuous infusion of low-dose human atrial natriuretic peptide from the initiation of CPB effectively maintained postoperative renal function. Efforts to develop a surgical strategy to shorten the operative time may also be important. The present study has some limitations. This is a retrospective study, and intraoperative information on factors that could affect postoperative renal function, such as blood pressure, inotropic agents, the composition of CPB, cannulation strategy, urine outflow, renal protection agents, and the amount of transfusion, which have been
previously reported as independent risk factors for postoperative AKI after cardiac operations, is missing from the database. In addition, this study uses preoperative and intraoperative factors, although postoperative factors obviously also affect renal dysfunction. Further studies that incorporate these data missing from the present study are warranted to establish a more precise risk model of postoperative AKI after valvular operations using CPB. In conclusion, postoperative AKI is highly associated with operative mortality and morbidity rates. Preexisting renal dysfunction, heart failure, and atherosclerosispromoting factors such as ASO, DM, smoking, and operation time were identified as significant risk factors for postoperative AKI. A risk index based on these factors should be useful for predicting the incidence of postoperative AKI and can play a role in designing an operative strategy that prevents AKI. Facilities affiliated with the Osaka Cardiovascular Surgery Research Group (OSCAR): Department of Cardiovascular Surgery, Osaka University Graduate School of Medicine, Sakurabashi Watanabe Hospital, Osaka Police Hospital, Osaka General Hospital, Osaka Rosai Hospital, Hyogo College of Medicine, KKR Sapporo Medical Center, Kure Medical Center, Osaka Minami Medical Center, Osaka National Hospital, Yao Tokushukai Hospital, Kawachi General Hospital, Kinan Hospital, Fukui Cardiovascular Center, Higashi Takarazuka Satoh Hospital, Kansai Rosai Hospital, Otemae Hospital, Ehime University Graduate School of Medicine, Tottori University Faculty of Medicine, and JCHO Osaka Hospital.
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injury in pediatric cardiac patients. Ann Thorac Surg 2014;97:202–10. Nah CW, Ti LK, Liu W, Ng RR, Shen L, Chew ST. A clinical score to predict acute kidney injury after cardiac surgery in a Southeast-Asian population. Interact Cardiovasc Thorac Surg 2016;23:757–61. Kristovic D, Horvatic I, Husedzinovic I, et al. Cardiac surgery-associated acute kidney injury: risk factors analysis and comparison of prediction models. Interact Cardiovasc Thorac Surg 2015;21:366–73. Pannu N, Graham M, Klarenbach S, et al. A new model to predict acute kidney injury requiring renal replacement therapy after cardiac surgery. CMAJ 2016;188:1076–83. Weir MR, Aronson S, Avery EG, Pollack CV Jr. Acute kidney injury following cardiac surgery: role of perioperative blood pressure control. Am J Nephrol 2011;33:438–52. Mangano CM, Diamondstone LS, Ramsay JG, Aggarwal A, Herskowitz A, Mangano DT. Renal dysfunction after myocardial revascularization: risk factors, adverse outcomes, and hospital resource utilization. The Multicenter Study of Perioperative Ischemia Research Group. Ann Intern Med 1998;128:194–203. Hilberman M, Derby GC, Spencer RJ, Stinson EB. Sequential pathophysiological changes characterizing the progression from renal dysfunction to acute renal failure following cardiac operation. J Thorac Cardiovasc Surg 1980;79:838–44. Zanardo G, Michielon P, Paccagnella A, et al. Acute renal failure in the patient undergoing cardiac operation: prevalence, mortality rate, and main risk factors. J Thorac Cardiovasc Surg 1994;107:1489–95. Sirivella S, Gielchinsky I, Parsonnet V. Mannitol, furosemide, and dopamine infusion in postoperative renal failure complicating cardiac surgery. Ann Thorac Surg 2000;69:501–6. Loef BG, Epema AH, Navis G, Ebels T, van Oeveren W, Henning RH. Off-pump coronary revascularization attenuates transient renal damage compared with on-pump coronary revascularization. Chest 2002;121:1190–4. Chertow GM, Lazarus JM, Christiansen CL, et al. Preoperative renal risk stratification. Circulation 1997;95:878–84. Ostermann ME, Taube D, Morgan CJ, Evans TW. Acute renal failure following cardiopulmonary bypass: a changing picture. Intensive Care Med 2000;26:565–71. Sezai A, Hata M, Niino T, et al. Influence of continuous infusion of low-dose human atrial natriuretic peptide on renal function during cardiac surgery: a randomized controlled study. J Am Coll Cardiol 2009;54:1058–64.
Background. Acute kidney injury (AKI) after valvular surgical procedures with cardiopulmonary bypass carries potentially high mortality and morbidity rates. This study investigated the risk factors for AKI, and the study investigators developed a risk index to predict postoperative AKI. Methods. A total of 1,484 consecutive non–dialysisdependent patients who underwent valvular operations using cardiopulmonary bypass between 2008 and 2011 were retrospectively investigated. The definition of AKI is newly required temporary hemodialysis or a creatinine level greater than 2.0 mg/dL with more than twofold elevation compared with the preoperative value. Results. Postoperative AKI occurred in 91 patients (6.1%), among whom new dialysis dependence occurred in 45 patients (3.1%), resulting in hospital death in 22 patients (48.9%), discharge with renal function recovery in 19 (42.2%), and permanent dialysis dependence in 4 (8.9%). The overall hospital mortality rate was 3.9%. The mortality rate in patients with postoperative AKI-related
complications and those who required new hemodialysis was 35.2% (32 of 91) and 48.9% (22 of 45), respectively, which was higher than in patients without AKI (1.9%; 26 of 1,393). Independent risk factors of postoperative AKI were smoking (odds ratio [OR], 2.008; p [ 0.0151), diabetes mellitus (OR, 2.730; p [ 0.0014), arteriosclerosis obliterans (OR, 4.351; p [ 0.0317), congestive heart failure (OR, 2.455; p [ 0.0052), estimated glomerular filtration rate less than or equal to 30 mL/min (OR, 4.855; p < 0.0001), and operation time longer than 8 hours (OR, 4.068; p [ 0.0005). The risk index based on these risk factors predicted postoperative AKI (area under the curve, 0.81) and new requirement of hemodialysis (area under the curve, 0.86). Conclusions. Based on these risk factors, the study investigators were able to predict the postoperative incidence of renal dysfunction after valvular operations with cardiopulmonary bypass.
P
ostoperative acute kidney injury (AKI) is a serious complication of cardiac surgical procedures that carries a high mortality rate [1, 2]. In various studies reporting the incidence of and risk factors for postoperative AKI after cardiac operations, cardiopulmonary bypass (CPB) has been established as a risk factor for postoperative renal impairment [1, 3–9]. In coronary artery bypass surgery, off-pump coronary artery bypass grafting has been reported to reduce postoperative AKI [10]. In the field of valvular surgery, most operations still require CPB, although transcatheter aortic valve implantation [11] and placement of a mitral clip [12], which can be performed off-pump, have been increasingly
promoted as alternative techniques. In clinical settings, non–dialysis-dependent patients with preexisting severe renal failure sometimes hesitate to undergo cardiac operations to avoid transition to permanent hemodialysis. However, the incidence of such transition postoperatively remains unclear. In the present study, we investigated the risk factors for AKI and the incidence of transition to permanent dialysis after valvular operations using CPB. The relationship between a risk index based on identified risk factors and the postoperative incidence of AKI was also investigated in hopes of improving clinical outcomes in this population.
Accepted for publication Feb 6, 2017.
Patients and Methods
*A complete list of the facilities affiliated with the Osaka Cardiovascular Surgery Research Group (OSCAR) appears at the end of this article.
Patients
Address correspondence to Dr Sawa, Department of Cardiovascular Surgery, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan; email: [email protected].
Between 2008 and 2011, 1,484 consecutive valvular surgical procedures (with and without concomitant operations) performed at Osaka University (Osaka, Japan) and
Ó 2017 by The Society of Thoracic Surgeons Published by Elsevier Inc.
(Ann Thorac Surg 2017;-:-–-) Ó 2017 by The Society of Thoracic Surgeons
0003-4975/$36.00 http://dx.doi.org/10.1016/j.athoracsur.2017.02.012
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its 22 associated facilities (Osaka Cardiovascular Surgery Research Group [OSCAR]) whose medical information was registered in the Japan Adult Cardiovascular Surgery Database (JACVSD) were retrospectively reviewed.
Definition The definitions of data in the present study coincide with those of the JACVSD, most of which are identical to those in The Society of Thoracic Surgeons National Database (available online at http://sts.org). The JACVSD definitions are also available online (http://www.jacvsd.umin. jp). The definition of AKI is new requirement of hemodialysis or a creatinine (Cr) level greater than 2.0 mg/dL with a more than twofold elevation compared with the preoperative value. Renal function is assessed by calculating the glomerular filtration rate (GFR) using revised equations for estimated GFR (eGFR) from serum creatinine for Japan, as follows: GFR ¼ 194 (Cr, mg/dL) 1.094 (age) 0.287 0.739 (if female) [13].
Statistical Analysis Values of variables are expressed as mean standard deviation or as percentages. Methods of univariate analysis included Student’s t test for continuous variables and the c2 test or Fisher’s exact test for categorical variables. Significant variables from the univariate analysis (p < 0.2) were subjected to multivariate analysis using the Cox binary logistic regression model. Statistical significance was assumed for a p value of less than 0.05. To assess the ability of significant variables from the multivariate analysis, the odds ratio (OR) was calculated. The validity of the risk index was examined using a receiver-operating characteristic (ROC) curve. Statistical analyses were performed using JMP 8.0 software (SAS Institute, Cary, NC).
Results Patients’ Characteristics Patients’ characteristics are listed in Table 1. The mean age was 69.3 12.5 years, and 52% of the patients were male. All patients were non–dialysis dependent. The percentage of patients with an eGFR of 30 mL/min or less was 11.4%, those with an eGFR between 30 and 60 mL/ min was 42.0%, and those with an eGFR of 60 mL/min or greater was 46.6%. Mean ejection fraction was 60.7% 14.7%. Congestive heart failure was observed in 328 patients (22.1%). Elective operations were performed in 1,399 patients (94.3%). Combined aortic surgical procedures and coronary artery bypass grafting were performed in 92 (6.2%) and 216 (14.6%) patients, respectively. Aortic valve replacement was performed in 785 patients (52.9%), mitral valve replacement in 331 (22.3%), and mitral reconstructive operations in 461 (31.1%). Mean operation time was 351 149.7 minutes, and the mean CPB time was 124.1 45.8 minutes. The postoperative hospital stay 28.4 26.3 days in the group without AKI and 45.7 34.9 days in the group with AKI (p < 0.001). The overall hospital mortality rate was 3.9% (Table 1).
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Incidence of Postoperative Acute Kidney Injury and Requirement of New Hemodialysis The incidence of postoperative AKI and new hemodialysis requirement is listed in Figure 1. Postoperative AKI occurred in 91 patients (6.1%), 45 of whom (3.1%) were newly dependent on dialysis, resulting in hospital death in 22 patients (48.9%), discharge with recovery of renal function in 19 (42.2%), and permanent dialysis dependence in 4 (8.9%). The incidence of AKI stratified according to GFR (GFR 30 mL/min, 30 to 60 mL/min, and 60 mL/min) was 20.7%. 5.8%, and 2.9%, respectively. Postoperative requirement for new dialysis in these patients was 14.8%, 2.2%, and 0.9%, respectively. The mortality rate related to postoperative AKI and new requirement of hemodialysis was 35.2% (32 of 91) and 48.9% (22 of 45), respectively, considerably higher than in patients without AKI (1.9%; 26 of 1,393).
Risk Factor Analysis Multivariate analysis of postoperative AKI (Table 2) showed that independent risk factors were smoking history (OR, 2.008; 95% confidence interval (CI), 1.144 to 3.524; p ¼ 0.0151), diabetes mellitus (DM) (OR, 2.730; 95% CI, 1.472 to 5.063; p ¼ 0.0014), arteriosclerosis obliterans (ASO) (OR, 4.351; 95% CI, 1.138 to 10.641; p ¼ 0.0317), congestive heart failure (OR, 2.455; 95% CI, 1.307 to 4.612; p ¼ 0.0052), eGFR of 30 mL/min or less (OR, 4.855; 95% CI, 2.599 to 9.068; p < 0.0001), and operation time longer than 8 hours (OR, 4.068; 95% CI, 1.842 to 8.982; p ¼ 0.0005).
Risk Index Development Based on the risk factor analysis, we developed a risk index for prediction of the incidence of postoperative AKI. To develop relative weights for the predictors in the renal risk index, we rounded the OR in the final multiple logistic model to the nearest integer. According to magnitude of the OR in the multivariate analysis, we weighed the factors as follows: smoking, 2 points; ASO, 4 points; DM, 2 points; heart failure, 2 points; eGFR of 30 mL/min or less, 5 points; operation time longer than 8 hours, 4 points.
Risk Index Including Preoperative and Intraoperative Risk Factors To investigate the validity of this risk index when including preoperative and intraoperative risk factors, we used all risk factors (ranging from 0 to 19 points), and the final model was evaluated using the area under the ROC curve (AUC), which represents the predictive ability. The AUC of postoperative AKI and new requirement of hemodialysis was 0.81 and 0.86, respectively (Fig 2A). The cohort was divided into three categories: low risk (score, 0 to 2: 871 patients), medium risk (score, 3 to 7: 480 patients), and high risk (score 8: 133 patients). The incidence of postoperative AKI in low-, medium-, and high-risk categories was 1.8%, 7.5%, and 28.8%, respectively (Fig 2B). The incidence of postoperative new requirement of dialysis in low-, medium-, and high-risk categories was 0.6%, 4.0%, and 15.9%, respectively (Fig 2B).
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Table 1. Patients’ Characteristics Characteristics Age Sex (male) Body surface area (m2) Smoking Diabetes mellitus Hypertension Hyperlipidemia Preoperative creatinine eGFR eGFR <30 30< eGFR <60 eGFR 60 Infectious endocarditis (active þ chronic) Infectious endocarditis (active) Chronic obstructive pulmonary disease Arteriosclerosis obliterans Carotid stenosis Liver dysfunction Cardiac condition Heart failure NYHA N/A I II III IV No. of diseased coronary vessels None One Two Three LV function (ejection fraction) Surgical procedure Single valve surgery Multivalve surgery Aortic valve surgery Replacement Root reconstruction valve conduit Repair or reconstruction Reconstruction with valve sparing Mitral valve surgery Replacement Annuloplasty only Reconstruction with annuloplasty Reconstruction without annuloplasty Valvectomy Tricuspid valve surgery Annuloplasty only Replacement Reconstruction with annuloplasty Valvectomy
All Cases (n ¼ 1,484)
AKI (n ¼ 91)
non-AKI (n ¼ 1,394)
p Value Second
69.3 12.5 772 (52.0%) 1.54 0.2 475 (32.0%) 297 (20.0%) 859 (57.9%) 443 (29.9%) 0.97 0.66
72.3 10.9 54 (59.3) 1.58 0.2 41 (45.1) 39 (42.9) 61 (67.0) 33 (36.3) 1.56 0.92
69.1 12.5 718 (51.5) 1.54 0.2 434 (31.1) 258 (18.5) 798 (57.2) 410 (29.4) 0.94 0.62
<0.001 NS NS 0.006 <0.001 NS NS <0.001
169 623 692 124 92 130 92 58 45
(11.4%) (42.0%) (46.6%) (8.4%) (6.2%) (8.7%) (6.2%) (3.9%) (3.0%)
35 36 20 15 14 8 16 10 7
(38.5) (39.6) (22.0) (16.5) (15.4) (8.8) (17.6) (11.0) (7.7)
134 587 672 109 78 122 76 48 38
(9.6) (42.1) (48.2) (7.8) (5.6) (8.8) (5.5) (3.4) (2.7)
<0.001 . . <0.001 <0.001 NS <0.001 <0.001 0.008 <0.001
328 (22.1%)
39 (42.9)
289 (20.7)
60 248 737 354 85
2 13 39 24 13
58 235 698 330 72
(4.0%) (16.7%) (49.7%) (23.9%) (5.7%)
(2.2) (14.3) (42.9) (26.4) (14.3)
(4.2) (16.9) (50.1) (23.7) (5.2)
0.017
0.004 . . . 0.002
926 (75.2%) 150 (12.2%) 71 (5.8%) 82 (6.7%) 60.7 14.7
43 (47.3) 11 (12.1) 10 (11.0) 8 (8.8) 55.9 17.3
883 (63.3) 139 (10.0) 61 (4.4) 74 (5.3) 61.1 14.1
886 (59.7%) 598 (40.3%)
52 39
834 559
NS .
785 34 10 4
(52.9%) (2.3%) (0.7%) (0.3%)
44 6 1 1
(48.4) (6.6) (1.1) (1.1)
741 28 9 3
(53.2) (2.0) (0.6) (0.2)
0.013
331 196 265 20 2
(22.3%) (13.2%) (17.9%) (1.3%) (0.1%)
26 14 14 1 0
(28.6) (15.4) (15.4) (1.1) (0.0)
305 182 251 19 2
(21.9) (13.1) (18.0) (1.4) (0.1)
0.013 . . . .
480 9 6 1
(32.3%) (0.6%) (0.4%) (0.1%)
25 1 2 1
(27.5) (1.1) (2.2) (1.1)
455 8 4 0
(32.6) (0.6) (0.3) (0.0)
0.003 . . .
. .
(Continued)
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Table 1. Continued Characteristics Pulmonary valve surgery Replacement Concomitant surgery Thoracic surgery Coronary artery bypass grafting Arrhythmia surgery Urgency Elective Urgent Emergency Salvage Transfusion Operation time (min) Cross-clamp time (min) Lowest temperature during CPB <30 C Circulatory arrest Perfusion time (min) Postoperative course Postoperative mechanical circulatory support Hospital stay after surgery (days) Dead Status at discharge Not affected (modified Rankin scale grade 0–3) Moderately affected (modified Rankin scale grade 4) Severely affected (modified Rankin scale grade 5)
All Cases (n ¼ 1,484)
AKI (n ¼ 91)
non-AKI (n ¼ 1,394)
8 (0.6%)
0 (0.0)
8 (0.6)
92 (6.2%) 216 (14.6%) 338 (22.8%)
9 (9.9) 22 (24.2) 15 (16.5)
83 (6.0) 194 (13.9) 323 (23.2)
p Value Second
NS 0.017 . .
1,399 (94.3%) 42 (2.8%) 42 (2.8%) 1 (0.1%) 1,241 (83.6%) 351.2 149.7 124.1 45.8 196 (13.2) 21 (1.4) 177.2 63.4
78 (85.7) 7 (7.7) 6 (6.6) 0 (0.0) 87 (95.6) 456.4 165.3 147.6 57.9 19 (20.9) 2 (2.1) 222.1 88.5
1,321 (94.8) 35 (2.5) 36 (2.6) 1 (0.1) 1,154 (82.8) 344.3 146.1 122.6 44.6 177 (12.7) 19 (1.3) 174.2 60.2
0.004 . . . 0.001 <0.001 <0.001 0.026 NS <0.001
12 (0.8) 28.6 32.5 58 (3.9%)
7 (7.7) 45.7 34.9 32 (35.2)
5 (0.4) 28.4 26.3 26 (1.9)
<0.001 <0.001 <0.001
1,353 (91.2%) 56 (3.9%) 17 (1.2%)
49 (53.8) 8 (8.8) 2 (2.2)
AKI ¼ acute kidney injury; CPB ¼ cardiopulmonary bypass; eGFR ¼ estimated glomerular filtration rate; not applicable; NS ¼ not significant; NYHA ¼ New York Heart Association (functional class).
Risk Index Including Preoperative Risk Factors To investigate the validity of this risk index when including preoperative risk factors, we used all risk factors (ranging from 0 to 15 points), and the final model was evaluated using the AUC to represent predictive ability. The AUC of postoperative AKI and new requirement of hemodialysis was 0.77 and 0.82, respectively (Fig 3A). The cohort was once again divided into the three categories: low risk (score, 0 to 2: 964 patients), medium risk (score, 3 to 6: 367 patients), and high risk (score 7: 153 patients). The incidence of postoperative AKI for low-, medium-, and high-risk categories was 2.7%, 7.4%, and 28.8%, respectively (Fig 3B). The incidence of postoperative new requirement of dialysis for low-, medium-, and high-risk patients was 1.1%, 3.3%, and 15.0%, respectively (Fig 3B). The relationships among operation time, incidence of postoperative AKI, and new requirement of hemodialysis stratified by the risk scores are listed in Figure 4. Regarding postoperative AKI, in patients whose operation time was within 5 hours, the incidence in the low-, medium-, and high-risk groups was 0.7%, 2.7%, and 9.5%; in patients whose operation time was from 5 to 8 hours, the incidence was 2.8%, 7.6%, and 27.1%; and for those whose operation time was longer than 8 hours, the incidence was 10.8%, 18.0%, and 40.0%, respectively. With respect to postoperative new requirement of
1,304 (93.5) 48 (3.4) 15 (1.1)
<0.001 . .
LV ¼ left ventricular;
N/A ¼
hemodialysis, the incidence in low-, medium-, and highrisk groups, respectively, was as follows: operation time within 5 hours, 0.2%, 0.7%, and 7.1%; operation time from 5 to 8 hours, 0.9%, 3.2%, and 17.2%; and operation time longer than 8 hours, 6.5%, 11.4%, and 20.0%.
Comment Among morbidities after cardiac surgical procedures, AKI greatly worsens the patient’s prognosis. Although various studies have been reported regarding the risk model of AKI after open heart surgery, most are concerned with outcomes of coronary artery bypass grafting and aortic or pediatric surgery, rather than focusing on valvular surgery [4, 14–18]. In an aging society, valvular surgical procedures have been increasing and are also undergoing drastic changes in response to the advent of transcatheter surgical procedures such as transcatheter aortic valve implantation and the mitral clip. Many earlier reports have shown the predicted incidence of AKI after operations using CPB stratified by each risk score, as displayed in Figures 2 and 3 in the present study. However, few studies have shown the relationship between the incidence of AKI and operation time stratified by the risk score as displayed in Figure 4, which shows that the incidence of AKI in patients classified even at the same
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Fig 1. Incidence of postoperative renal dysfunction. (AKI ¼ acute kidney injury; CPB ¼ cardiopulmonary bypass; eGFR ¼ estimated glomerular filtration rate; HD ¼ hemodialysis; Pts ¼ patients.)
risk score increases in proportion to the operation time. We believe that this result may contribute to the selection of surgical procedure, especially in cases of valvular surgical procedures requiring other concomitant operations such as coronary artery and arrhythmia correction procedures. Various studies on the incidence of and risk factors for postoperative AKI after cardiac surgical procedures, according to each article’s definition, have been published
[19]. In the present study we determined five preoperative risk factors (preexisting renal dysfunction, smoking, ASO, DM, heart failure) and one intraoperative risk factor (prolonged operation time). Apart from our findings reported herein, longer duration of CPB, intraoperative hemodynamic instability (eg, multiple inotrope use, support of intraaortic balloon pumping, hypotension), and transfusion (eg, red blood cells, platelets, fresh frozen plasma) have been reported as risk factors for postoperative AKI
Table 2. Univariate and Multivariate Analysis of Postoperative Acute Kidney Injury Factors Preoperative factors Age 70 y Smoking Diabetes mellitus With insulin Infective endocarditis Active Arteriosclerosis obliterans Liver dysfunction Cardiovascular operative history Heart failure NYHA (III) Coronary artery disease (2 vessel) Poor LV function Emergency or urgent operation eGFR 30 Intraoperative factors CABG Lowest body temperature >30 Perfusion time >5 h Operative time >8 h AKI ¼ acute kidney injury; rate; LV ¼ left ventricular;
Univariate p Value
Multivariate p Value
Odds Ratio (95% CI)
Risk Scores
0.0404 0.0059 <0.0001 <0.0001 0.0038 0.0002 <0.0001 0.0075 0.0006 <0.0001 0.0019 0.0009 0.0019 0.0003 <0.0001
NS 0.0151 0.0014 NS NS NS 0.0317 NS NS 0.0052 NS NS NS NS <0.0001
. 2.008 (1.1443.524) 2.730 (1.4725.063) . . . 4.351 (1.13810.641) . . 2.455 (1.3074.612) . . . . 4.855 (2.5999.068)
. 2 3 . . . 4 . . 2 . . . . 5
. . . 4.068 (1.8428.982)
. . . 4
0.0072 0.00053 <0.0001 <0.0001
NS NS NS 0.0005
CABG ¼ coronary artery bypass grafting; CI ¼ confidence interval; eGFR ¼ estimated glomerular filtration NS ¼ not significant; NYHA ¼ New York Heart Association (functional class).
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Fig 2. Receiver-operator characteristic curve for postoperative renal dysfunction and incidence of acute kidney injury (AKI) and new hemodialysis (HD) including preoperative and intraoperative risk predictors. (AUC ¼ area under the curve.)
after cardiac operations [19]. Similar to previous analyses assessing risk, preexisting renal damage is an important predictor of renal events for well-defined reasons. Smoking history, ASO, and DM, well known as risk factors for atherosclerosis, may also be speculated as having adverse effects on the renal artery and its function. Among the other predictors, congestive heart failure is consistent with previous studies indicating the untoward effect of reduced renal perfusion [20]. In addition, prolonged operation time is identified as an intraoperative predictor, probably because of the magnitude of the inflammatory response in the kidney. As already mentioned, CPB time is a well-established independent risk factor for postoperative AKI. In the present study, CPB time was significant in univariate but not multivariate analysis (Table 2). Although CPB time is certainly crucial in affecting postoperative renal dysfunction, we believe that longer operation time may be a stronger predictor because the extended duration means that the operation requires both longer CPB time and a longer time for hemostasis, which require increased transfusion and lead to deterioration of postoperative renal function. Fig 3. Receiver-operator characteristic curve for postoperative renal dysfunction and incidence of acute kidney injury (AKI) and new hemodialysis (HD) including preoperative risk predictors. (AUC ¼ area under the curve.)
We also investigated the relationship between the incidence of postoperative AKI and the requirement for new hemodialysis, stratified according to the risk index including preoperative risk factors. In patients with low and medium risk (score, 0 to 6), the incidence of renal dysfunction is relatively low within 8 hours, but it increases drastically after 8 hours. In patients with a high risk score (7), the incidence rises to higher levels after more than 300 minutes of operative time. Therefore a shorter operation is desirable, especially in patients with a high risk score. The incidence of AKI necessitating dialysis after cardiac operations is relatively low (1% to 5%) [21–24]. Approximately 50% of patients with postoperative AKI in the present study required temporary or permanent hemodialysis, although the incidence of transition to permanent hemodialysis reported in the literature to date has been uncertain. In the present study, half of the patients requiring postoperative new hemodialysis died while in hospital, and approximately 20% of survivors transitioned to permanent hemodialysis (4 of 1,484: 0.4% overall). The fate of the patients newly requiring
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Fig 4. Relationship between operation time and postoperative renal dysfunction stratified by risk index including preoperative risk factors. (AKI ¼ acute kidney injury; HD ¼ hemodialysis.)
hemodialysis as reported in the historical literature once seemed catastrophic. The benchmark reports conducted by Chertow and colleagues [25] reported a mortality rate of 63% at 30 days for those patients requiring hemodialysis compared with 4.3% for patients without renal dysfunction. A slightly more recent report by Mangano and associates [20] identified similar mortality rates among patients with postoperative renal failure. The hospital stay appears longer than that in the Western world. The longer stays in hospital could be attributed to the fact that for patients in Japan, most medical costs are covered by national health insurance. There has been little progress in recent years in reducing the incidence of AKI, improving the prognosis of affected patients, or identifying it earlier in its pathologic course [2, 3, 26]. More recently published data suggest that perioperative blood pressure lability influences both the risk of postoperative renal dysfunction and 30-day mortality rates [19]. The present study reveals congestive heart failure as one of the preoperative risk factors. Therefore, if the possibility of medical treatment exists, surgical intervention after optimized heart failure may be more desirable from the perspective of prevention of renal function impairment. Medical management in the perioperative period has been reported to exert a beneficially protective effect on the kidney. Sezai and colleagues [27] reported that continuous infusion of low-dose human atrial natriuretic peptide from the initiation of CPB effectively maintained postoperative renal function. Efforts to develop a surgical strategy to shorten the operative time may also be important. The present study has some limitations. This is a retrospective study, and intraoperative information on factors that could affect postoperative renal function, such as blood pressure, inotropic agents, the composition of CPB, cannulation strategy, urine outflow, renal protection agents, and the amount of transfusion, which have been
previously reported as independent risk factors for postoperative AKI after cardiac operations, is missing from the database. In addition, this study uses preoperative and intraoperative factors, although postoperative factors obviously also affect renal dysfunction. Further studies that incorporate these data missing from the present study are warranted to establish a more precise risk model of postoperative AKI after valvular operations using CPB. In conclusion, postoperative AKI is highly associated with operative mortality and morbidity rates. Preexisting renal dysfunction, heart failure, and atherosclerosispromoting factors such as ASO, DM, smoking, and operation time were identified as significant risk factors for postoperative AKI. A risk index based on these factors should be useful for predicting the incidence of postoperative AKI and can play a role in designing an operative strategy that prevents AKI. Facilities affiliated with the Osaka Cardiovascular Surgery Research Group (OSCAR): Department of Cardiovascular Surgery, Osaka University Graduate School of Medicine, Sakurabashi Watanabe Hospital, Osaka Police Hospital, Osaka General Hospital, Osaka Rosai Hospital, Hyogo College of Medicine, KKR Sapporo Medical Center, Kure Medical Center, Osaka Minami Medical Center, Osaka National Hospital, Yao Tokushukai Hospital, Kawachi General Hospital, Kinan Hospital, Fukui Cardiovascular Center, Higashi Takarazuka Satoh Hospital, Kansai Rosai Hospital, Otemae Hospital, Ehime University Graduate School of Medicine, Tottori University Faculty of Medicine, and JCHO Osaka Hospital.
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