Lesion Renal 17 PDF
Lesion Renal 17 PDF
Lesion Renal 17 PDF
Abstract
Background: Acute kidney injury (AKI) after cardiac surgery is associated with increased morbidity and mortality.
Although morbidity of AKI after off-pump coronary artery bypass grafting (OPCAB) has been investigated, little is
known about risk factors for AKI after OPCAB. To identify risk factors for AKI, we examined the association between
perioperative variables and AKI after OPCAB.
Findings: We reviewed the medical records of consecutive adult patients who underwent isolated OPCAB
between January 2010 and February 2013 in a single institute, retrospectively. The primary outcome was the
incidence of AKI evaluated using Acute Kidney Injury Network classifications during the first 48 h postoperatively. We
investigated preoperative and intraoperative variables, including hemodynamic parameters, as potential risk factors for
AKI. The relationship between candidates of AKI and incidence of AKI was examined by multivariate logistic
regression analysis.
A total of 298 patients were enrolled in this study. Acute kidney injury occurred in 47 patients (15.7%). Multivariate logistic
regression analysis showed that intraoperative furosemide administration (odds ratio [OR], 5.163; 95% confidence interval,
2.171 to 12.185; P < 0.001] and diabetes mellitus (OR, 1.954; 95% confidence interval, 1.004 to 3.880; P = 0.049) were
significantly associated with AKI.
Conclusions: Intraoperative furosemide administration and diabetes mellitus were significantly associated with AKI in
patients who had received OPCAB.
Keywords: AKI, Acute kidney injury, Off-pump coronary artery bypass grafting, Furosemide
CPB, OPCAB requires heart displacement during anasto- systemic perfusion pressure by tilting the surgical table
mosis of grafts, potentially resulting in intraoperative and administering intravenous fluids followed by the ad-
hemodynamic instability and global hypoperfusion [19]. ministration of noradrenaline as a first-choice vasopressor.
However, few studies have focused on the relationship
between intraoperative hemodynamic instability and the Statistical analysis
incidence of AKI after OPCAB [20–24]. Continuous variables are expressed as a mean ± standard
In this retrospective study, we examined the associ- deviation [SD]. Categorical variables are expressed as a
ation between AKI after OPCAB with perioperative vari- number and percentage. Initially, all preoperative vari-
ables, including intraoperative parameters related to ables and intraoperative variables, except continuous
hemodynamic instability, such as the cardiac index and variables in the arterial blood gas analysis during sur-
lactate levels. gery, were divided into dichotomous data according to a
clinically significant cut point. To identify which vari-
Methods ables were associated with AKI, data were examined
This study was approved by the institutional review using the chi-square test or Fisher’s exact test for dichot-
board of our center in June 2013 (Number: M25-025). omous data, or univariate logistic regression analysis for
We retrospectively analyzed the data of consecutive intraoperative continuous data. Among the variables
adult patients who underwent isolated OPCAB between with a P value < 0.20 in univariate analysis, we selected
January 2010 and February 2013 at the center. We ex- covariates in multivariable logistic regression analysis
cluded patients with end-stage kidney disease with an considering known risk factors or relationships to
estimated glomerular filtration rate (eGFR) < 15 mL/ hemodynamics during surgery to determine independent
min/1.73 m2 or requiring dialysis, a history of previous risk factors for AKI. To avoid overfitting of the model,
cardiac surgery, congenital heart disease, and minimally we allowed a maximum of one variable per each 10
invasive cardiac surgery. We focused on patients with events. Model calibration was assessed using the
AKI after OPCAB as a primary outcome. The incidence Hosmer-Lemeshow goodness-of-fit test. A two-sided P
of AKI was diagnosed until 48 h postoperatively, and the value < 0.05 was considered statistically significant. All
staging of AKI was evaluated until 7 days postopera- statistical analyses were performed using SPSS software,
tively, according to the criteria proposed by Acute Kid- version 21.0 (IBM, Armonk, NY, USA).
ney Injury Network (AKIN) classifications [25] as AKIN
stage 1: increased creatinine level > 50% or 0.3 mg/dL Results
from baseline, or urine output < 0.5 mL/kg/h continuing Of 339 patients enrolled, 41 were excluded from the
more than 6 h; AKIN stage 2: increased creatinine level analysis, because the patients had end-stage kidney dis-
by > 100%, or urine output < 0.5 mL/kg/h over 12 h; and ease with an eGFR < 15 mL/min/1.73 m2, required dialy-
AKIN stage 3: increased creatinine level by > 200% or sis (n = 23), or had a history of cardiac surgery (n = 10),
serum creatinine level > 4 mg/dL with an acute increase minimally invasive cardiac surgery (n = 2), or OPCAB
of > 0.5 mg/dL, new-onset renal replacement therapy, with another surgery (n = 6). Two hundred ninety-eight
urine output < 0.3 mL/kg/h over 24 h, or anuria over patients remained in this study. Approximately 16% of
12 h. We examined preoperative and intraoperative patients had AKI, and most of them were classified as
variables for associations with AKI after OPCAB. Cat- stage 1 according to the AKIN criteria (Table 1).
egories of preoperative risk factors of AKI included age, Details related to the surgery and anesthesia are shown
body mass index, preoperative comorbidities, labora- in Table 2. Most patients had 3-vessels coronary disease
tory data, emergent surgery, coronary angiography or left main coronary artery involvement; therefore, they
within 7 days, and perioperative intra-aortic balloon underwent more than three grafts of anastomosis. All
pumping (IABP). For intraoperative variables, we in- patients were operated through a median sternotomy in-
vestigated the use of diuretics, vasopressors, cardiac cision, and the left internal thoracic artery was anasto-
index (CI), base excess (BE), serum lactate levels, and mosed to the left anterior descending coronary artery;
hemoglobin levels during surgery. this was subsequently followed by revascularization of
the left circumflex artery and right coronary artery. Ex-
Anesthesia technique posure of the grafting site and motionless surgical field
All patients underwent general anesthesia. We routinely required deep pericardial traction sutures and commer-
use a direct arterial blood catheter, transesophageal cially available stabilizers. A coronary shunt was rou-
echocardiography, and a pulmonary artery catheter with a tinely inserted before graft anastomosis.
continuous CI measurement. When transient circulatory Results of univariate analysis of preoperative demo-
failure and global hypoperfusion occur during manipula- graphic characteristics and intraoperative variables are
tion of the heart or anastomosis, we usually maintain shown in Table 3. The following three variables were
Kumada et al. JA Clinical Reports (2017) 3:55 Page 3 of 8
Table 1 Postoperative AKI and perioperative creatinine value intraoperative furosemide administration and diabetes
Incidence of AKI a
47 (15.7%) mellitus as independent risk factors for AKI (Table 4).
Stage 1 42 The Hosmer-Lemeshow goodness-of-fit test showed an
Stage 2 4
adequate performance of the predictive model
(P = 0.914).
Stage 3 1
We further reviewed the patients who were adminis-
Preoperative serum creatinine level (mg/dL) 0.94 ± 0.34 tered furosemide based on the above results. In all 28
Highest postoperative serum creatinine level (mg/dL) 1.07 ± 0.47 patients with furosemide, only single injection, not con-
Data are presented as a number (%) or mean ± standard deviation tinuous infusion, was used to administer furosemide,
AKI acute kidney injury
a
Eleven of 40 patients in stage 1 and half of patients in stage 2 met only urine
and the average dosage of furosemide was 10 ± 4.90 mg.
criteria without the clinical increase in the serum creatinine level. One patient Although this retrospective study could not clearly spe-
in stage 3 had anuria and received renal replacement therapy on cify the reason why furosemide was used for oliguria,
postoperative day 2
hyperkalemia, or hypervolemia during surgery, only four
patients (14.2%) experienced continued oliguria during
significantly associated with AKI in univariate analysis surgery (total urine output during surgery < 0.5 ml/kg/
(P < 0.05): diabetes mellitus, perioperative IABP, and in- h). Since diuretics were usually used to treat oliguria, it
traoperative furosemide administration. Besides these was difficult to interpret the exact relationship between
three variables, preoperative hypoalbuminemia (albumin furosemide and postoperative AKI, whether the fur-
level < 4 g/dL), the highest intraoperative lactate level, osemide was either risk factor, or simply risk marker.
and total urine output during surgery were likely to in- Therefore, we also investigated the preoperative kidney
crease the incidence of AKI (P < 0.20). However, since function and intraoperative urine output in the patients
urine output itself was involved in the diagnosis of AKI given the furosemide or carperitide, the another diuretic
after surgery from the end of surgery to 48 h after sur- commonly used for oliguria as well as furosemide
gery, we thought intraoperative urine output as clearly (Table 5). The patients given either furosemide or car-
inappropriate for a risk factor to be analyzed by multi- peritide demonstrated significantly smaller amount of
variate analysis. We entered the five variables with a P urine output and lower preoperative eGFR than those
value < 0.20 except total urine output into multivariable without the diuretics. However, carperitide but furosem-
logistic regression analysis, because five covariates were ide did not increase the incidence of AKI, and intraoper-
within permissible range to avoid overfitting the model ative urine output did not increase the incidence of AKI
based on occurrence of 47 outcomes in this study. Mul- in univariate analysis (Table 3), suggesting that furosem-
tivariable logistic regression analysis identified ide itself might have any potential effect on the inci-
dence of AKI.
Table 2 Clinical features of the surgery and anesthesia (n = 298)
Operative time (min) 290 ± 55 Discussion
Anesthesia time (min) 386 ± 61 In this retrospective study, multivariable logistic regres-
Number of anastomoses 3.6 ± 0.9 sion analysis identified intraoperative furosemide ad-
ministration and diabetes mellitus as independent risk
Bypass area
factors for AKI. Intraoperative hemodynamic parame-
LAD 291 (100%)
ters, CI, BE, lactate, and hemoglobin levels were not
LCX 255 (85.6%) associated with AKI.
RCA 226 (75.8%) Diabetes mellitus is well known as a systemic disease,
Emergent surgery 61 (21.0%) which frequently causes the diabetic nephropathy,
Maintenance of anesthesia neuropathy, retinopathy, and increased the cardiovas-
cular events and mortality [26, 27]. Diabetic nephropa-
Propofol 255 (85.6%)
thy, the leading cause of chronic kidney disease
Sevoflurane 44 (14.8%)
worldwide, is one of the most common complications
Noradrenaline 274 (91.9%) in diabetic patient, and the diabetic patient is more
Maximum dose (μg/kg/min) 0.11 ± 0.11 likely to suffer from renal damage than those without
Dopamine 267 (89.6%) diabetes, even if the nephropathy was not evident [28,
Maximum dose (μg/kg/min) 2.4 ± 1.2 29]. Indeed, previous studies suggested that diabetes is
an important risk factor for postoperative AKI after
Other inotropes 31 (10.4%)
cardiac surgery [4, 5, 22, 30–32]. Recently, Hertzberg et
Data are presented as a mean ± standard deviation or number (%)
LAD left anterior descending artery, LCX left circumflex artery, RCA right
al. conducted the large observational study including
coronary artery 36,106 patients with CABG, which suggested that type
Kumada et al. JA Clinical Reports (2017) 3:55 Page 4 of 8
Table 3 Preoperative demographic characteristics and intraoperative variables in patients with or without AKI
Variable AKI (n = 47) No AKI (n = 251) P value
Age > 75 years 8 (17.0%) 52 (20.7%) 0.5620
Female sex 10 (21.3%) 50 (19.9%) 0.8315
2
BMI > 25 kg/m 20 (42.6%) 84 (33.5%) 0.2303
Comorbid disease
Hypertension 45 (95.7%) 226 (90.0%) 0.2111
Hyperlipidemia 40 (85.1%) 216 (86.1%) 0.8637
Diabetes mellitus 29 (61.7%) 107 (42.6%) 0.0160
Ejection fraction < 35% 6 (12.8%) 22 (8.8%) 0.4131
Atrial fibrillation 2 (4.3%) 12 (4.8%) 1.0000
Peripheral vascular disease 9 (19.2%) 70 (27.9%) 0.2128
Cerebrovascular disease 9 (19.2%) 58 (23.1%) 0.5508
Preoperative laboratory data
Hemoglobin level < 8 g/dL 0 (0%) 1 (0.4%) 1.0000
Albumin level < 4 g/dL 21 (44.7%) 85 (33.9%) 0.1551
2
eGFR mL/min/1.73 m 62.6 ± 20.4 64.2 ± 17.5 0.5745
eGFR < 60 mL/min/1.73 m2 17 (36.1%) 95 (37.9%) 0.8274
Preoperative clinical condition
CAG within 7 days 13 (27.7%) 62 (24.7%) 0.6680
Emergent operation 12 (25.5%) 49 (19.5%) 0.3487
Intra-aortic balloon pumping 12 (25.5%) 34 (13.6%) 0.0369
Intraoperative variable
Lowest BE level − 3.7 ± 2.0 − 3.4 ± 2.4 0.3491
Highest lactate level (mmol/L) 1.5 ± 0.6 1.3 ± 0.6 0.1807
Lowest hemoglobin level (g/dL) 8.3 ± 0.9 8.2 ± 0.8 0.8708
2
Lowest CI < 1.8 (L/min/m ) 18 (41.9%) 84 (40.4%) 0.8576
Furosemide administration 13 (27.7%) 15 (6.0%) < 0.001
Carperitide administration 8 (17.0%) 28 (11.2%) 0.2574
Noradrenaline > 0.1 μg/kg/min 12 (25.5%) 84 (33.4%) 0.3126
Total urine output (ml) 1209 ± 948 1458 ± 873 0.0666
Data are presented as a mean ± standard deviation or number (%). Continuous data were assessed using univariate logistic regression analysis, and categorical
data were examined using the chi-square test or Fisher’s exact test
AKI acute kidney injury, BMI body mass index, eGFR estimated glomerular filtration rate, CAG coronary angiography, BE base excess, CI cardiac index
2 diabetes significantly increased the incidence of post- (OR, 1.954; 95% confidence interval, 1.00–3.880;
operative AKI defined by AKIN criteria after CABG P = 0.049). This result was consistent with previous
(OR 1.27; confidence interval 1.16–1.40) [30]. In the studies [4, 5, 22, 30–32].
present study, diabetes mellitus was significantly asso- We also identified the use of furosemide during sur-
ciated with postoperative AKI after cardiac surgery gery as an independent risk factor for postoperative AKI.
Table 5 The patients demographics given the furosemide or carperitide during surgery.
Variable Diuretics (+) Diuretics (-) P value
Furosemide administration n = 28 n = 270
Preoperative eGFR (mL/min/1.73 m2) 57.5 ± 21.1 64.6 ± 17.5 0.0457
Intraoperative urine output (ml) 763.3 ± 670.9 1487.5 ± 881.7 <0.001
Carperitide administration n = 36 n = 262
Preoperative eGFR (mL/min/1.73 m2) 45.4 ± 17.0 66.5 ± 16.5 <0.001
Intraoperative urine output (ml) 815.8 ± 794.1 1502.4 ± 870.0 <0.001
Data are presented as a mean ± standard deviation. Statistical analyses were performed by the unpaired Student’s t-test.
AKI = acute kidney injury; eGFR = estimated glomerular filtration rate.
Furosemide is a loop diuretic that inhibits the Na-K-2Cl regression analysis identified furosemide during CPB as
cotransporter system in the luminal membrane of the an independent predictor for postoperative AKI [6].
ascending limb of the loop of Henle [33, 34]. Furosemide Lassnigg et al. conducted a double-blind randomized,
has been widely prescribed to maintain or increase urine controlled trial of 126 patients with normal renal func-
output for both the risk and treatment of AKI, because tion undergoing elective cardiac surgery and found that
it may be needed to maintain patency of renal tubules a continuous infusion of furosemide was associated with
and prevent tubular obstruction and back-leak. In a higher rate of renal impairment [44]. They suggested
addition, furosemide may reduce renal tubular oxygen that the negative effect of furosemide was due to two
consumption by decreasing sodium reabsorption, which possible theories: first, neurohumoral activation of the
leads to less ischemic damage of the most vulnerable sympathetic and renin-angiotensin systems by furosem-
outer medullary tubular segments [35–38]. ide could increase peripheral vascular resistance, left
However, prior studies have failed to demonstrate a clin- ventricular afterload, and cardiac work, thus mediating a
ical benefit of furosemide in terms of mortality and renal decrease in cardiac output; and, second, the induction of
recovery of AKI and suggested a possible harmful effect of maldistribution of renal blood flow with diversion of me-
furosemide when used to prevent or treat AKI. [37–45] A dullary perfusion by a decrease in cortical vascular
previous multicenter, observational study that enrolled resistance may promote tubular dysfunction. These pre-
552 patients with AKI in intensive care units from the vious findings support our results [6, 37–45]. We retro-
Program to Improve Care in Acute Renal Disease (PIC- spectively examined recorded data at a single center,
ARD) study group demonstrated that the use of furosem- meaning that both causality and the mechanisms by
ide was associated with a significant increase in the risk of which furosemide had a detrimental effect on renal func-
death or non-recovery of renal function (odds ratio [OR], tion could not be analyzed in this study. However, a pos-
1.77; 95% confidence interval, 1.14 to 2.76) [39]. A recent sible explanation is that an unnatural increasing of urine
meta-analysis of 9 randomized, controlled trials of 849 pa- output may delay or mask the recognition of AKI, which
tients that compared furosemide with a placebo to prevent would forfeit an opportunity for optimal treatment
or treat acute renal failure concluded that furosemide did against the cause of AKI [39]. In addition, it has been
not reduce in-hospital mortality (relative risk 1.11, 95% proposed that furosemide may cause a decrease in the
confidence interval 0.92 to 1.33), the requirement for circulating volume and activate the neurohumoral
dialysis (relative risk 0.99, 95% confidence interval 0.80 to response, such as the sympathetic nervous system and
1.22), number of dialysis sessions required until recovery renin-angiotensin system, which could increase periph-
of renal function, proportion of patients remaining oli- eral vascular resistance, left ventricular afterload, and
guric, or length of hospital stay [40]. Based on these evi- decrease cardiac output [37, 44, 46–49].
dence, The Kidney Disease Improving Global Outcomes Although we aimed to investigate whether intra-
Clinical Practice Guideline for Acute Kidney Injury pro- operative hemodynamic instability during OPCAB af-
posed not using diuretics to prevent or treat AKI (1B rec- fected postoperative AKI, we were unable to identify
ommendation), except in the management of volume anything regarding an association between intraoperative
overload (2C recommendation) [38]. hemodynamic parameters and postoperative AKI. Intra-
Although most previous studies did not focus on the operative hemodynamic instability can cause the impair-
effect of furosemide on postoperative AKI, several stud- ment of renal perfusion, resulting in postoperative AKI. A
ies have implied a deleterious effect of furosemide in recent meta-analysis involving data of 4220 surgical pa-
cardiac operation [6, 44, 45]. Parolari et al. reported, tients in 20 studies examined whether perioperative
based on a prospective, observational study of 3219 hemodynamic optimization improved renal outcome and
patients after cardiac surgery, that multivariable logistic found that postoperative AKI was significantly reduced by
Kumada et al. JA Clinical Reports (2017) 3:55 Page 6 of 8
perioperative hemodynamic optimization compared with In conclusion, we found that intraoperative furosemide
that in the control group (OR 0.64; confidence interval administration and diabetes mellitus were independently
0.50 to 0.83; P = 0.0007) [50]. However, in our study, in- associated with AKI in patients undergoing OPCAB.
traoperative hemodynamic instability was not associated However, our findings in this retrospective study repre-
with postoperative AKI. Our inability to detect the impact sent only the possibility that furosemide during surgery
of intraoperative hemodynamic instability on renal func- affects postoperative AKI. Further prospective random-
tion in this study may be due to the temporal nature of ized trials are needed to investigate the effect of intraop-
the data collected within our hemodynamic parameters. erative furosemide administration on renal function, and
Although we investigated the lowest CI, lowest BE, and whether intraoperative hemodynamic variables are asso-
highest lactate levels intraoperatively, we did not review ciated with the incidence of AKI.
the duration of the unstable data, nor the quality of the
Abbreviations
data recovery. AKI: Acute kidney injury; AKIN: Acute Kidney Injury Network; BE: Base excess;
There were several limitations in this study. First, the CABG: Coronary artery bypass grafting; CAG: Coronary angiography;
number of patients was small and derived from a single CI: Cardiac index; CPB: Cardiopulmonary bypass; eGFR: Estimated glomerular
filtration rate; IABP: Intra-aortic balloon pumping; LAD: Left anterior
center. Even though many preoperative factors including descending artery; LCX: Left circumflex artery; ONCAB: On-pump CABG;
age, anemia, hypoalbuminemia, DM, chronic kidney dis- OPCAB: Off-pump coronary artery bypass grafting; RCA: Right coronary artery;
ease, chronic heart failure, and IABP have been reported SD: Standard deviation
as the independent risk factors for AKI in early studies, Acknowledgements
we could not identify the only two independent factors There are no contributors to be acknowledged.
[4, 5, 9, 21, 22]. There may be possible selection bias
Funding
and a lack of power. Second, data for the cardiac index None.
were missing in about 19% of the study populations that
included four patients with AKI. This may decrease the Authors’ contributions
YK and KY participated in the study design, data collection, data analysis, and
power of this study to evaluate this hemodynamic par- drafted the article. YS assisted in the data collection. YO assisted in the data
ameter as risk factors for AKI. Third, we did not analyze analysis and in drafting the paper. All authors approved the final version of
the intraoperative systemic blood pressure. Several previ- the manuscript for submission.
ous observational studies reported that lower mean ar- Ethics approval and consent to participate
terial pressure during surgery was involved in This study was approved by the institutional review board of National
postoperative AKI [51, 52]. However, we could not Cerebral and Cardiovascular Center, Suita, Japan in June 2013 (Approval
number: M25-025). The requirement for written informed consent was
collect the detailed data for arterial blood pressure waived by the institutional review board.
due to the form of this retrospective survey. Add-
itionally, we frequently altered the bed positioning to Competing interests
The authors declare that they have no competing interests.
maintain hemodynamic condition during anastomosis,
which readily affected the arterial blood pressure by
Publisher’s Note
changing the positional relation between introducer Springer Nature remains neutral with regard to jurisdictional claims in published
and right atrium. If the detailed data on arterial blood maps and institutional affiliations.
pressure was collected, the validity and reliability of
Author details
the data might not have been guaranteed. Thus, as 1
Department of Anesthesiology, National Cerebral and Cardiovascular Center,
the index indirectly reflecting systemic perfusion pres- 5-7-1, Fujishirodai, Suita, Osaka 565-8565, Japan. 2Department of Cardiac
sure, we investigated the dose of vasopressors, which Surgery, National Cerebral and Cardiovascular Center, 5-7-1, Fujishirodai,
Suita, Osaka 565-8565, Japan.
was not significantly associated with AKI in the
present study. Finally, this study was a retrospective, Received: 10 August 2017 Accepted: 28 September 2017
observational study, and thus, causality between fur-
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