ORIGINAL RESEARCH
Dynamic Predictive Scores for Cardiac Surgery–Associated Acute Kidney Injury Wuhua Jiang, MD;* Jie Teng, MD;* Jiarui Xu, MD; Bo Shen, MD; Yimei Wang, MD; Yi Fang, MD; Zhouping Zou, MD; Jifu Jin, MD; Yamin Zhuang, MD; Lan Liu, MD; Zhe Luo, MD; Chunsheng Wang, MD; Xiaoqiang Ding, MD
Background-—Cardiac surgery–associated acute kidney injury (CSA-AKI) is a common complication with a poor prognosis. In order to identify modifiable perioperative risk factors for AKI, which existing risk scores are insufficient to predict, a dynamic clinical risk score to allow clinicians to estimate the risk of CSA-AKI from preoperative to early postoperative periods is needed. Methods and Results-—A total of 7233 cardiac surgery patients in our institution from January 2010 to April 2013 were enrolled prospectively and distributed into 2 cohorts. Among the derivation cohort, logistic regression was used to analyze CSA-AKI risk factors preoperatively, on the day of ICU admittance and 24 hours after ICU admittance. Sex, age, valve surgery combined with coronary artery bypass grafting, preoperative NYHA score >2, previous cardiac surgery, preoperative kidney (without renal replacement therapy) disease, intraoperative cardiopulmonary bypass application, intraoperative erythrocyte transfusions, and postoperative low cardiac output syndrome were identified to be associated with CSA-AKI. Among the other 1152 patients who served as a validation cohort, the point scoring of risk factor combinations led to area under receiver operator characteristics curves (AUROC) values for CSA-AKI prediction of 0.74 (preoperative), 0.75 (on the day of ICU admission), and 0.82 (postoperative), and Hosmer–Lemeshow goodness-of-fit tests revealed a good agreement of expected and observed CSA-AKI rates. Conclusions-—The first dynamic predictive score system, with Kidney Disease: Improving Global Outcomes (KDIGO) AKI definition, was developed and predictive efficiency for CSA-AKI was validated in cardiac surgery patients. ( J Am Heart Assoc. 2016;5: e003754 doi: 10.1161/JAHA.116.003754) Key Words: acute kidney injury • cardiac surgery • risk factor • risk score
A
cute kidney injury (AKI) is a common complication after cardiac surgery, with reported incidences between 8.9% and 39% as well as mortality of 3.8% to 54.4%, and even slight renal function changes were reported to affect short- and long-term outcome after cardiac surgery.1–3 Because early prediction in those patients at high risk of developing cardiac surgery–associated acute kidney injury (CSA-AKI) may enable
From the Departments of Nephrology (W.J., J.T., J.X., B.S., Y.W., Y.F., Z.Z., J.J., X.D.), Cardiac Surgery Intensive Care Unit (Y.Z., L.L., Z.L.), and Cardiovascular Surgery (C.W.), Zhongshan Hospital, Shanghai Medical College, Fudan University, Shanghai, China; Shanghai Kidney and Dialysis Institute, Shanghai, China (W.J., J.T., J.X., B.S., Y.W., Y.F., Z.Z., J.J., X.D.); Shanghai Kidney and Blood Purification Laboratory, Shanghai, China (J.T., Y.F., X.D.). *Dr Jiang and Dr Teng contributed equally to this work. Correspondence to: Xiaoqiang Ding, MD, Department of Nephrology, Zhongshan Hospital, Shanghai Medical College, Fudan University, No 180 Fenglin Rd, Shanghai, China. E-mail: [email protected] Received April 21, 2016; accepted July 8, 2016. ª 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
DOI: 10.1161/JAHA.116.003754
prevention of complications, in the last 2 decades various predictive models have been developed to forecast CSA-AKI or renal replacement therapy (RRT)-AKI after cardiac surgery,4–9 in which adequate predictive power was validated among whites.10,11 However, by now, the predictive value for estimating AKI, RRT-AKI, or death incidence of 5 established models, including the method published by Palomba et al,7 the Cleveland Clinic score,8 the scoring system published by Mehta et al,6 the simplified renal index score,9 and the EURO score12 in other racial cohorts after cardiac surgery is uncertain. Possible reasons might include the following. (1) There was no consensus in the definition of AKI when those models were developed. In the AKICS score, AKI was defined as “an increase of serum creatine (Cr) levels above 2.0 mg/ dL in patients with baseline serum Cr lower than 1.5 mg/dL.” In patients with baseline serum Cr between 1.5 and 3.0 mg/ dL, AKI was defined as “a serum Cr increase of 50% over the baseline value.” In the new 2012 Kidney Disease: Improving Global Outcomes (KDIGO) AKI definition,13 urine output, as another indicator besides serum creatine, was not utilized to define AKI in Palomba’s study, and AKI may be missed. (2) With the recognition of intraoperative and postoperative risk Journal of the American Heart Association
1
AKI Prediction After Cardiac Surgery
Jiang et al
Patients and Methods Patients In our prospective study we included 7233 patients who were divided into a derivation cohort (6081 patients between January 2010 and October 2012) and a validation cohort (1152 patients between November 2012 and April 2013); all were admitted to the Zhongshan Hospital, Shanghai Medical College, Fudan University. The study was approved by the ethical committee of the Zhongshan Hospital, and all participants provided written informed consent. Inclusion criteria were adult patients who underwent coronary artery bypass grafting (CABG), off-pump coronary artery bypass (OPCAB), valve surgery, or valve combined with CABG surgery. Excluded were patients with previous heart transplantation, preoperative mechanical ventilation or tracheotomy, preoperative defibrillator or ventricular assist devices, preoperative RRT, preoperative liver dysfunction, or sepsis.
Data Collection The clinical characteristics of both derivation and validation cohorts have been collected and were extracted from the database of Zhongshan Hospital cardiac surgery. All data were checked twice by medical personnel (postgraduate and resident doctor) before being admitted to the database. We collected data including sex, age, weight, length of stay, length of ICU stay, and outcome; preoperative data including diagnosis, comorbidities including hypertension, diabetes mellitus, atrial fibrillation, endocarditis, coronary artery disease, cerebral vascular disease, anemia, chronic obstructive pulmonary disease, kidney disease without renal replacement therapy; and laboratory reports including estimated glomerular filtration rate (eGFR), which were calculated with CKD-EPI formulas,15 in addition to New York Heart DOI: 10.1161/JAHA.116.003754
Association (NYHA) functional classification, left ventricular ejection fraction (LVEF), preoperative congestive heart failure, preoperative intra-aortic balloon pump (IABP), previous cardiac surgery history, recent contrast media (CM) exposure, and renal toxic drug exposure. Intraoperative data included emergency surgery, procedure type, cardiopulmonary bypass (CPB) application and time, transfusion, and fluid balance; postoperative data comprised low cardiac output syndrome (LCOS), central venous pressure, medicine application, mechanical ventilation, RRT, and renal recovery. AKI was defined according to the KDIGO guideline13 as any of the following: increase in SCr by ≥0.3 mg/dL (≥26.5 lmol/L) within 48 hours; or increase in SCr to ≥1.5 times baseline that is known or presumed to have occurred within the prior 7 days or urine volume 50%
5030 (82.7%)
978 (84.9%)
35< LVEF ≤50
968 (15.9%)
157 (13.6%)
LVEF ≤35%
83 (1.3%)
17 (1.5%)
Previous cardiac surgery
84 (1.4%)
25 (2.2%)
CM exposure
2464 (40.5%)
395 (34.3%)
11 (0.2%)
3 (0.3%)
Comorbidities
Heart function
Intraoperative Emergency Procedure Valve
3975 (65.4%)
794 (68.9%)
CABG
1527 (25.1%)
325 (28.2%)
OPCAB
286 (4.7%)
45 (3.9%)
Valve and CABG
293 (4.8%)
47 (4.1%)
CPB
4083 (67.1%)
792 (68.8)
Erythrocyte transfusion, U
1 (0, 2)
1 (0, 2)
LCOS
158 (2.6%)
35 (3.1%)
CVP, cm H2O
9 (7, 11)
10 (8, 10)
170 (2.8%)
39 (3.4%)
Postoperative
Prognosis 28-day mortality
AKI indicates acute kidney injury; CABG, coronary artery bypass grafting; CM, contrast media; COPD, chronic obstructive pulmonary disease; CPB, cardiopulmonary bypass; CVD, cerebral vascular disease; CVP, central venous pressure by ICU admittance; DM, diabetes mellitus; eGFR, estimated glomerular filtration rate, as was calculated based on the CKD-EPI formulas; LCOS, low cardiac output syndrome; LVEF, left ventricular ejection fraction; NYHA, New York Heart Association; OPCAB, off-pump coronary artery bypass.
DOI: 10.1161/JAHA.116.003754
characteristics of both cohorts were showed in Table 1. The incidence of CSA-AKI and mortality in the derivation cohort were 35.5% (2159/6081) and 2.8% (170/6081), whereas in the validation cohort they were 33.0% (380/1152) and 3.4% (39/1152).
Risk Factor Analysis The perioperative characteristics of the derivation cohort are presented in Table 2. We categorized the following variables for subgroup observation: age (≤40, 41–60, 61–80, ≥81), estimated GFR (>60, >30 to ≤60, ≤30 mL/min), and LVEF (>50, 36–50, ≤35). There were statistically significant differences between the CSA-AKI patients and the unaffected group regarding sex, age, preoperative kidney function, some comorbidities such as hypertension and COPD, preoperative heart function, CM exposure, procedure type, perioperative erythrocyte transfusion, postoperative central venous pressure, and short-term mortality (Table 2). All these risk factors were brought into a multivariate analysis for predicting CSA-AKI. The multivariate logistic regression analysis was conducted at 3 time points: preoperative, ICU admittance, and 24 hours after ICU admittance; the statistically significant risk factors identified by the analysis are shown in Table 3, which shows that male sex, age, kidney disease without RRT, NYHA score >2, previous cardiac surgery, valve and CABG procedure, application of CPB, erythrocyte transfusion, and postoperative LCOS at the indicated time points were risk factors for CSA-AKI development (Table 3).
Score Development Next we developed a point system for predicting CSA-AKI occurrence with the regression coefficient data from the multivariable regression analyses of the derivative cohort patients (Table 4). Depending on the scores, the risks of CSA-AKI development were categorized into low, medium, and high in accordance with the practically observed incidence of CSA-AKI (Table 5). The preoperative predictive risks of CSA-AKI occurrence were low with 0 to 1 patient (9.5%), medium with 2 to 3 patients (22.1%), and high with ≥4 patients (37.3%). The predictive risks of CSA-AKI development at the day of ICU admission were low with 0 to 4 patients (11.5%), medium with 5 to 9 patients (42.6%), and high with ≥10 patients (83.3%). The postoperative predictive risks for developing CSA-AKI were low with 0 to 4 patients (11.6%), medium with 5 to 9 patients (44.2%), and high with ≥10 patients (88.8%). The efficiency of the scores for predicting medium and high risk for CSA-AKI improved with the procedure progress and additional risk factors being added. We further analyzed the score models at the 3 time
Journal of the American Heart Association
3
ORIGINAL RESEARCH
Table 1. Clinical Characteristics of Derivation and Validation Cohort
AKI Prediction After Cardiac Surgery
Jiang et al ORIGINAL RESEARCH
Table 2. Characteristics of the Patients in the Derivation Cohort Entire Cohort (N=6081)
No AKI (N=3922)
AKI (N=2159)
P Value
Male
3767 (61.9%)
2254 (57.5%)
1513 (70.1%)
Dynamic Predictive Scores for Cardiac Surgery–Associated Acute Kidney Injury Wuhua Jiang, MD;* Jie Teng, MD;* Jiarui Xu, MD; Bo Shen, MD; Yimei Wang, MD; Yi Fang, MD; Zhouping Zou, MD; Jifu Jin, MD; Yamin Zhuang, MD; Lan Liu, MD; Zhe Luo, MD; Chunsheng Wang, MD; Xiaoqiang Ding, MD
Background-—Cardiac surgery–associated acute kidney injury (CSA-AKI) is a common complication with a poor prognosis. In order to identify modifiable perioperative risk factors for AKI, which existing risk scores are insufficient to predict, a dynamic clinical risk score to allow clinicians to estimate the risk of CSA-AKI from preoperative to early postoperative periods is needed. Methods and Results-—A total of 7233 cardiac surgery patients in our institution from January 2010 to April 2013 were enrolled prospectively and distributed into 2 cohorts. Among the derivation cohort, logistic regression was used to analyze CSA-AKI risk factors preoperatively, on the day of ICU admittance and 24 hours after ICU admittance. Sex, age, valve surgery combined with coronary artery bypass grafting, preoperative NYHA score >2, previous cardiac surgery, preoperative kidney (without renal replacement therapy) disease, intraoperative cardiopulmonary bypass application, intraoperative erythrocyte transfusions, and postoperative low cardiac output syndrome were identified to be associated with CSA-AKI. Among the other 1152 patients who served as a validation cohort, the point scoring of risk factor combinations led to area under receiver operator characteristics curves (AUROC) values for CSA-AKI prediction of 0.74 (preoperative), 0.75 (on the day of ICU admission), and 0.82 (postoperative), and Hosmer–Lemeshow goodness-of-fit tests revealed a good agreement of expected and observed CSA-AKI rates. Conclusions-—The first dynamic predictive score system, with Kidney Disease: Improving Global Outcomes (KDIGO) AKI definition, was developed and predictive efficiency for CSA-AKI was validated in cardiac surgery patients. ( J Am Heart Assoc. 2016;5: e003754 doi: 10.1161/JAHA.116.003754) Key Words: acute kidney injury • cardiac surgery • risk factor • risk score
A
cute kidney injury (AKI) is a common complication after cardiac surgery, with reported incidences between 8.9% and 39% as well as mortality of 3.8% to 54.4%, and even slight renal function changes were reported to affect short- and long-term outcome after cardiac surgery.1–3 Because early prediction in those patients at high risk of developing cardiac surgery–associated acute kidney injury (CSA-AKI) may enable
From the Departments of Nephrology (W.J., J.T., J.X., B.S., Y.W., Y.F., Z.Z., J.J., X.D.), Cardiac Surgery Intensive Care Unit (Y.Z., L.L., Z.L.), and Cardiovascular Surgery (C.W.), Zhongshan Hospital, Shanghai Medical College, Fudan University, Shanghai, China; Shanghai Kidney and Dialysis Institute, Shanghai, China (W.J., J.T., J.X., B.S., Y.W., Y.F., Z.Z., J.J., X.D.); Shanghai Kidney and Blood Purification Laboratory, Shanghai, China (J.T., Y.F., X.D.). *Dr Jiang and Dr Teng contributed equally to this work. Correspondence to: Xiaoqiang Ding, MD, Department of Nephrology, Zhongshan Hospital, Shanghai Medical College, Fudan University, No 180 Fenglin Rd, Shanghai, China. E-mail: [email protected] Received April 21, 2016; accepted July 8, 2016. ª 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
DOI: 10.1161/JAHA.116.003754
prevention of complications, in the last 2 decades various predictive models have been developed to forecast CSA-AKI or renal replacement therapy (RRT)-AKI after cardiac surgery,4–9 in which adequate predictive power was validated among whites.10,11 However, by now, the predictive value for estimating AKI, RRT-AKI, or death incidence of 5 established models, including the method published by Palomba et al,7 the Cleveland Clinic score,8 the scoring system published by Mehta et al,6 the simplified renal index score,9 and the EURO score12 in other racial cohorts after cardiac surgery is uncertain. Possible reasons might include the following. (1) There was no consensus in the definition of AKI when those models were developed. In the AKICS score, AKI was defined as “an increase of serum creatine (Cr) levels above 2.0 mg/ dL in patients with baseline serum Cr lower than 1.5 mg/dL.” In patients with baseline serum Cr between 1.5 and 3.0 mg/ dL, AKI was defined as “a serum Cr increase of 50% over the baseline value.” In the new 2012 Kidney Disease: Improving Global Outcomes (KDIGO) AKI definition,13 urine output, as another indicator besides serum creatine, was not utilized to define AKI in Palomba’s study, and AKI may be missed. (2) With the recognition of intraoperative and postoperative risk Journal of the American Heart Association
1
AKI Prediction After Cardiac Surgery
Jiang et al
Patients and Methods Patients In our prospective study we included 7233 patients who were divided into a derivation cohort (6081 patients between January 2010 and October 2012) and a validation cohort (1152 patients between November 2012 and April 2013); all were admitted to the Zhongshan Hospital, Shanghai Medical College, Fudan University. The study was approved by the ethical committee of the Zhongshan Hospital, and all participants provided written informed consent. Inclusion criteria were adult patients who underwent coronary artery bypass grafting (CABG), off-pump coronary artery bypass (OPCAB), valve surgery, or valve combined with CABG surgery. Excluded were patients with previous heart transplantation, preoperative mechanical ventilation or tracheotomy, preoperative defibrillator or ventricular assist devices, preoperative RRT, preoperative liver dysfunction, or sepsis.
Data Collection The clinical characteristics of both derivation and validation cohorts have been collected and were extracted from the database of Zhongshan Hospital cardiac surgery. All data were checked twice by medical personnel (postgraduate and resident doctor) before being admitted to the database. We collected data including sex, age, weight, length of stay, length of ICU stay, and outcome; preoperative data including diagnosis, comorbidities including hypertension, diabetes mellitus, atrial fibrillation, endocarditis, coronary artery disease, cerebral vascular disease, anemia, chronic obstructive pulmonary disease, kidney disease without renal replacement therapy; and laboratory reports including estimated glomerular filtration rate (eGFR), which were calculated with CKD-EPI formulas,15 in addition to New York Heart DOI: 10.1161/JAHA.116.003754
Association (NYHA) functional classification, left ventricular ejection fraction (LVEF), preoperative congestive heart failure, preoperative intra-aortic balloon pump (IABP), previous cardiac surgery history, recent contrast media (CM) exposure, and renal toxic drug exposure. Intraoperative data included emergency surgery, procedure type, cardiopulmonary bypass (CPB) application and time, transfusion, and fluid balance; postoperative data comprised low cardiac output syndrome (LCOS), central venous pressure, medicine application, mechanical ventilation, RRT, and renal recovery. AKI was defined according to the KDIGO guideline13 as any of the following: increase in SCr by ≥0.3 mg/dL (≥26.5 lmol/L) within 48 hours; or increase in SCr to ≥1.5 times baseline that is known or presumed to have occurred within the prior 7 days or urine volume 50%
5030 (82.7%)
978 (84.9%)
35< LVEF ≤50
968 (15.9%)
157 (13.6%)
LVEF ≤35%
83 (1.3%)
17 (1.5%)
Previous cardiac surgery
84 (1.4%)
25 (2.2%)
CM exposure
2464 (40.5%)
395 (34.3%)
11 (0.2%)
3 (0.3%)
Comorbidities
Heart function
Intraoperative Emergency Procedure Valve
3975 (65.4%)
794 (68.9%)
CABG
1527 (25.1%)
325 (28.2%)
OPCAB
286 (4.7%)
45 (3.9%)
Valve and CABG
293 (4.8%)
47 (4.1%)
CPB
4083 (67.1%)
792 (68.8)
Erythrocyte transfusion, U
1 (0, 2)
1 (0, 2)
LCOS
158 (2.6%)
35 (3.1%)
CVP, cm H2O
9 (7, 11)
10 (8, 10)
170 (2.8%)
39 (3.4%)
Postoperative
Prognosis 28-day mortality
AKI indicates acute kidney injury; CABG, coronary artery bypass grafting; CM, contrast media; COPD, chronic obstructive pulmonary disease; CPB, cardiopulmonary bypass; CVD, cerebral vascular disease; CVP, central venous pressure by ICU admittance; DM, diabetes mellitus; eGFR, estimated glomerular filtration rate, as was calculated based on the CKD-EPI formulas; LCOS, low cardiac output syndrome; LVEF, left ventricular ejection fraction; NYHA, New York Heart Association; OPCAB, off-pump coronary artery bypass.
DOI: 10.1161/JAHA.116.003754
characteristics of both cohorts were showed in Table 1. The incidence of CSA-AKI and mortality in the derivation cohort were 35.5% (2159/6081) and 2.8% (170/6081), whereas in the validation cohort they were 33.0% (380/1152) and 3.4% (39/1152).
Risk Factor Analysis The perioperative characteristics of the derivation cohort are presented in Table 2. We categorized the following variables for subgroup observation: age (≤40, 41–60, 61–80, ≥81), estimated GFR (>60, >30 to ≤60, ≤30 mL/min), and LVEF (>50, 36–50, ≤35). There were statistically significant differences between the CSA-AKI patients and the unaffected group regarding sex, age, preoperative kidney function, some comorbidities such as hypertension and COPD, preoperative heart function, CM exposure, procedure type, perioperative erythrocyte transfusion, postoperative central venous pressure, and short-term mortality (Table 2). All these risk factors were brought into a multivariate analysis for predicting CSA-AKI. The multivariate logistic regression analysis was conducted at 3 time points: preoperative, ICU admittance, and 24 hours after ICU admittance; the statistically significant risk factors identified by the analysis are shown in Table 3, which shows that male sex, age, kidney disease without RRT, NYHA score >2, previous cardiac surgery, valve and CABG procedure, application of CPB, erythrocyte transfusion, and postoperative LCOS at the indicated time points were risk factors for CSA-AKI development (Table 3).
Score Development Next we developed a point system for predicting CSA-AKI occurrence with the regression coefficient data from the multivariable regression analyses of the derivative cohort patients (Table 4). Depending on the scores, the risks of CSA-AKI development were categorized into low, medium, and high in accordance with the practically observed incidence of CSA-AKI (Table 5). The preoperative predictive risks of CSA-AKI occurrence were low with 0 to 1 patient (9.5%), medium with 2 to 3 patients (22.1%), and high with ≥4 patients (37.3%). The predictive risks of CSA-AKI development at the day of ICU admission were low with 0 to 4 patients (11.5%), medium with 5 to 9 patients (42.6%), and high with ≥10 patients (83.3%). The postoperative predictive risks for developing CSA-AKI were low with 0 to 4 patients (11.6%), medium with 5 to 9 patients (44.2%), and high with ≥10 patients (88.8%). The efficiency of the scores for predicting medium and high risk for CSA-AKI improved with the procedure progress and additional risk factors being added. We further analyzed the score models at the 3 time
Journal of the American Heart Association
3
ORIGINAL RESEARCH
Table 1. Clinical Characteristics of Derivation and Validation Cohort
AKI Prediction After Cardiac Surgery
Jiang et al ORIGINAL RESEARCH
Table 2. Characteristics of the Patients in the Derivation Cohort Entire Cohort (N=6081)
No AKI (N=3922)
AKI (N=2159)
P Value
Male
3767 (61.9%)
2254 (57.5%)
1513 (70.1%)
