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J Thorac Cardiovasc Surg 2007;134:1554-1561
© 2007 The American Association for Thoracic Surgery

Surgery for Acquired Cardiovascular Disease

RIFLE criteria for acute kidney injury in aortic arch surgery

^a Division of Thoracic and Cardiovascular Surgery, University of Florida, Gainesville, Fla
^b Division of Critical Care Medicine, University of Florida, Gainesville, Fla
^c Division of Nephrology, University of Florida, Gainesville, Fla
^d Division of Biostatistics, University of Florida, Gainesville, Fla.

Read at the Eighty-seventh Annual Meeting of The American Association for Thoracic Surgery, Washington, DC, May 5–9, 2007.

Received for publication May 4, 2007; revisions received August 7, 2007; accepted for publication August 15, 2007.

^_* Address for reprints: Thomas M. Beaver, MD, MPH, Associate Professor, Division of Thoracic and Cardiovascular Surgery, University of Florida, PO Box 100286, Gainesville, FL 32610-0286. (Email: beavetm{at}surgery.ufl.edu).

	Abstract

Top Abstract Introduction Patients and Methods Results Discussion References

 
Objective: The RIFLE criteria are new international consensus definitions for acute kidney injury introduced to facilitate research across disciplines. We identified risk factors for acute kidney injury, renal replacement therapy, and mortality using the RIFLE criteria (RIFLE = risk, injury, failure, loss, end stage) in patients undergoing deep hypothermic circulatory arrest for aortic arch reconstruction.

Methods: A single-center retrospective cohort study of 267 patients undergoing aortic arch surgery with deep hypothermic circulatory arrest was conducted between July 2001 and October 2005. Known predictors (age, chronic kidney disease, surgery status, redo, diabetes, hypertension, blood transfusion, bypass, and deep hypothermic circulatory arrest time) were used in multivariate logistic regression models for acute kidney injury, renal replacement therapy, and mortality.

Results: Mean age was 64 years (range 23–89 years) with 166 men (62%). Seventy-five (28%) had RIFLE scores of I or F, and 22 (8%) required dialysis. Risk factors for acute kidney injury were hypertension (odds ratio [OR] = 2.17; 95% confidence intervals [CI], 1.14–4.15), chronic kidney disease (OR = 9.04; 95% CI, 1.97–41.59), packed red blood cells greater than 5 units (OR = 2.37; 95% CI, 1.20-4.69), and admission creatinine/Modification of Diet in Renal Disease predicted creatinine ratio greater than 1 (OR = 3.54; 95% CI, 1.95–6.45). Risk factors for mortality were age (per 10 years) (OR = 2.35; 95% CI, 1.35–4.06), AKI (RIFLE class R, I, or F) (OR = 4.60; 95% CI, 1.34–15.77), and cerebrovascular accident (OR = 19.1; 95% CI, 4.96–73.58). Mortality increased with each RIFLE stratification (RIFLE class 0 = 3%, R = 9%, I = 12%, and F = 38%).

Conclusions: Acute kidney injury as defined according to the RIFLE classification is a risk factor for mortality and will be useful in future studies of renal dysfunction in thoracic aortic surgery.

	Introduction

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More than 30 years have elapsed since deep hypothermic circulatory arrest (DHCA) was introduced for cerebral protection during aortic arch surgery.¹ Improved surgical and anesthetic techniques have facilitated increasingly complex aortic reconstructions with decreased morbidity and mortality.^2-4 However, postoperative acute kidney injury (AKI) remains a significant problem in the setting of DHCA, with an incidence ranging from 8% to 50%, although various definitions have been used.^5-7 Renal dysfunction leads to increased postoperative morbidity and mortality, and patients requiring renal replacement therapy (RRT) have mortality as high as 64%.^2,8-13

Several studies have examined AKI after DHCA, with multiple definitions including the following: 50% increase in serum creatinine above baseline^5,14; 25% reduction in calculated creatinine clearance⁶; and need for dialysis.¹⁵ The variety of definitions hinders comparison between studies of kidney injury.¹⁴ Accordingly, the Acute Dialysis Quality Initiative Workgroup set forth a new international consensus definition for renal injury (RIFLE criteria), which stratifies renal failure into three grades of increasing severity of acute kidney injury (R = risk, I = injury, F = failure) and two outcome classes (L = loss, and E = end-stage kidney disease) (Table 1). The three grades of severity for AKI are based on changes in either serum creatinine or urine output from baseline.¹⁶

	Patients and Methods

Top Abstract Introduction Patients and Methods Results Discussion References

 
After Institutional Review Board approval, the medical records of patients undergoing thoracic aortic surgery at Shands Hospital at the University of Florida between July 2001 and October 2005 were retrospectively reviewed. During this period, 281 patients required DHCA for operations involving the aortic arch, and they comprise the cohort for the present analysis. Patients who died intraoperatively were excluded, inasmuch as no change in renal function could be identified. It should be noted that patients with a history of advanced chronic kidney disease (CKD stage 4 with estimated glomerular filtration rate [GFR] < 30 ml · min^–1 · 1.73 m^–2) or CKD stage 5 (long-term RRT) were also excluded. The rationale for this exclusion was that it is already known that patients with severe kidney disease defined as CKD stage 4 or 5 are already on or will progress to RRT and have poor outcomes.¹⁸ Patients with CKD stages 1 to 3 with or without AKI were included in the analysis inasmuch as the emphasis was to evaluate these patients with either preoperative normal renal function or only mild-to-moderate impairment. In total, 14 patients were excluded; therefore 267 patients were included in the RIFLE analysis.

Demographic and operative variables previously reported to be associated with postoperative renal dysfunction were compiled into the cardiac surgery database, which was managed by an experienced research nurse.^19,20 Demographic variables included age, gender, previous history of diabetes mellitus, hypertension (defined as patients with a documented history of hypertension previously being treated with an antihypertensive agent), cerebrovascular disease (defined by history of stroke or transient ischemic attack or known carotid occlusive disease > 50%), peripheral vascular disease, and chronic obstructive pulmonary disease; predicted serum creatinine according to the Modification of Diet in Renal Disease (MDRD) formula,²¹ history of CKD (defined above), primary operation versus reoperation ("redo"), use of aprotinin (Trasylol; Bayer, West Haven, Conn) or epsilon aminocaproic acid (Amicar; Xanodyne, Florence, Ky), and surgical status (elective versus emergency). Operative variables measured were: cardiopulmonary bypass (CPB) time, aortic crossclamp time, DHCA time, and need for more than 5 units of packed red blood cells (pRBCs) intraoperatively and/or first 7 days postoperatively. Patients were classified according to the maximum RIFLE (RIFLE_max) class (risk = R, injury = I, or failure = F) reached during the first 7 days after the operation. The RIFLE class was determined on the basis of the lowest GFR criteria by using the change in serum creatinine levels (Table 1).¹⁷

End Points
The primary outcomes analyzed were AKI, need for postoperative RRT, and in-hospital mortality. Need for reoperation during the same hospitalization and postoperative cerebrovascular accident (CVA) as determined by a formal neurologic evaluation were recorded as well.

Operative Procedure
Elective ascending and aortic arch operations were performed through a standard median sternotomy with dual-stage venous cannulation of the right atrium. Epiaortic scanning was used in ascending aortic aneurysms before aortic cannulation to confirm the absence of mural thrombus or calcification. Acute ascending aortic dissections were cannulated via an axillary or femoral artery. Before cannulation, heparin was administered (350 IU/kg). CPB was initiated only after assuring kaolin-activated clotting times were greater than 480 seconds. Almost all patients received aprotinin, typically "full dose" (2 x 10⁶ units intravenous load, 2 x 10⁶ units in the pump prime, and 5 x 10⁵ units/h); a minority of patients in our early experience received epsilon aminocaproic acid. Cardioplegic arrest was obtained with handheld antegrade cardioplegia catheters in the coronary ostia and with retrograde cardioplegia catheters in the coronary sinus; cardioplegic solution was redosed at 20-minute intervals via the retrograde catheter. Patients were monitored with cerebral oximetry and intraoperative electroencephalography. Temperature monitoring included nasopharyngeal, rectal, and bladder probes. Circulatory arrest was initiated after confirming no cerebral activity on the electroencephalogram with nasopharyngeal temperature at 18°C. Retrograde cerebral perfusion via a snared superior vena cava cannula was used when circulatory arrest times were greater than 20 minutes.

Data Analysis
A trained registered nurse database manager reviewed records of demographic, intraoperative, and postoperative variables, which were subsequently assembled in our institutional Microsoft Excel database (Microsoft, Redmond, Wash). Data were then exported to Statistica for analysis (StatSoft, Inc, Tulsa, Okla). Demographic and operative variables were compared among four groups (RIFLE classes 0, R, I, and F) using analysis of variance and the ² or Fisher exact tests where appropriate for continuous and categorical variables, respectively. Risk factors of AKI (defined by RIFLE classes R, I, or F) were determined by univariate logistic regression. Known risk factors for renal dysfunction and univariate predictors with P values < .05 in the present analysis were then entered into a logistic regression model to identify independent risk factors for AKI. Odds ratios (OR) and 95% confidence intervals (CI) were calculated. The same methods were used to identify variables independently associated with RRT and mortality. The model for RRT did not include AKI, as by definition all patients who require RRT are considered to be in RIFLE class F. To determine an independent effect with regard to mortality, we incorporated AKI into the mortality logistic regression model in addition to other significant variables (Table 2).

	Results

Top Abstract Introduction Patients and Methods Results Discussion References

Mortality rates increased with worsening severity of renal injury according to RIFLE_max classification: 4 of 138 (3%) RIFLE_max class 0, 5 of 54 (9%) RIFLE_max class R, 4 of 33 (12%) RIFLE class I, and 16 of 42 (38%) RIFLE_max class F patients died, respectively (Figure 1). Breakdown of patients according to RIFLE severity score and mortality data are presented in Table 4.

View larger version (10K): [in this window] [in a new window]   Figure 1. Final disposition according to RIFLE classification.

	Discussion

Top Abstract Introduction Patients and Methods Results Discussion References

 
Renal complications after aortic surgery are common; however, the multitude of definitions used has complicated comparison between series.²² The purpose of this report was to validate the new international consensus RIFLE classification scheme for AKI in the setting of aortic arch surgery. The RIFLE criteria were established in 2004 by the Acute Dialysis Quality Initiative, incorporating both laboratory and clinical parameters to assess renal function. A recent report used the RIFLE system in a contemporary cardiac surgery population¹⁷; however, in that series the majority of patients were at low risk for renal complications. The present study examines patients undergoing aortic arch surgery at high risk for renal injury and found the incidence of AKI as defined by any RIFLE category (R, I, or F) to be 48%, which was over twofold greater than the earlier series. This finding is not unexpected, inasmuch as both aortic surgery and DHCA are known to be independent risk factors for renal dysfunction.^20,23

The logistic regression model identified hypertension, chronic kidney disease, pRBCs greater than 5 units, and ratio admission creatinine/MDRD predicted creatinine greater than 1 as independent risk factors for renal injury, all of which are in accordance with earlier reports.^6,19 Predictors for RRT also included CKD, pRBCs greater than 5 units, and ratio admission creatinine/MDRD predicted creatinine greater than 1. Assuming a GFR between 75 and 100 mL/min, the MDRD formula can be used to predict a normal baseline creatinine. Patients whose admission creatinine was greater than MDRD predicted creatinine were at increased risk for AKI and RRT, suggesting that even subtle abnormalities in creatinine values may portend adverse outcomes with respect to renal function. Total pRBCs greater than 5 units was found by Mora Mangano and associates⁶ to be independently associated with renal dysfunction. In their discussion, they concluded, however, that there was no direct causality between blood transfusion and renal dysfunction; rather this finding was a reflection of hypovolemia, thought to be the cause for renal dysfunction.⁶ Similarly, we concur that increased total pRBCs, while used as a lifesaving measure, can be a surrogate marker for the very critically ill nature of the patients requiring such volume of blood products. However, there is evidence from a nonrandomized trial that increased RBC transfusion may worsen morbidity and mortality rates in a population of patients undergoing isolated coronary artery bypass grafting. Postulated explanations for adverse outcomes related to transfusion include proinflammatory end-organ damage and an adverse immunomodulatory effect on T-cell function.²⁴

Interestingly, the present series found redo surgical status associated with a decreased need for postoperative RRT, which is not consistent with other large series.¹⁹ We propose the following explanation for this inconsistency. Patients in this series predominantly required the use of DHCA for one of two disease processes: (1) acute aortic dissection and (2) aneurysmal aortic disease. Patients who had redo operations were more likely to undergo elective aneurysm repair. In comparison, patients with acute aortic dissection less frequently had redo operations and more frequently were operated on in an emergency setting, occasionally in profound shock.

We found that 22 (8%) patients required postoperative RRT (either hemodialysis or continuous venovenous hemofiltration), similar to other large series of patients undergoing aortic arch reconstructions.^25-27 Among patients requiring RRT postoperatively, 13 (59%) died. This figure underscores the bleak prognostic implications of RRT after cardiovascular surgery, and postoperative RRT has previously been found to independently predict mortality.¹¹ Others have reported similar mortality rates in patients requiring RRT postoperatively, ranging from 28% in a routine coronary bypass population²⁸ to 57% in patients undergoing DHCA for aortic arch aneurysm repair.²⁷

AKI, advanced age, and postoperative CVA all represent an independent association with mortality in this series. Advanced age is a widely known risk factor for perioperative mortality. RRT is a documented risk factor for mortality, and in this series 8% of the patients required RRT. To avoid confounding, we included AKI but not RRT in the logistic regression model for mortality. Given the findings in this study, we conclude that even less severe renal dysfunction as defined by AKI (RIFLE classes R, I, or F) is independently associated with mortality. Considering that 48% of this cohort met criteria for AKI using the RIFLE definition, this suggests that a large number of patients in the setting of DHCA are at jeopardy for adverse outcomes including mortality. Increasing mortality was noted with progressive RIFLE class as patients with no detectable renal dysfunction (RIFLE class 0) experienced a mortality of 3%; however, this increased proportionately in RIFLE classes R (9%), I (12%), and F (38%), respectively. Others have documented increased mortality with increasing RIFLE classification in noncardiac surgery patients²⁹ and in more routine cardiac surgery populations.¹⁷ We have shown a similar result in a more homogeneous population of patients, who all underwent DHCA for aortic arch repair.

The safety of aprotinin in cardiac surgery remains controversial.^30,31 Aprotinin was incorporated into the logistic regression model as a variable, but no association was identified. Because a majority of patients in this series received aprotinin and only a small number did not receive it, we had low power to detect any significant effect of aprotinin in regard to renal dysfunction or mortality.

The RIFLE classification system also includes a differentiation between RIFLE outcome categories L (loss, temporary dialysis) and E (end-stage permanent dialysis), which were not included because this information was not available in our retrospective database. This is a limitation of the study, because it is not readily known whether these two outcomes represent a different long-term risk for mortality. In addition, it is unclear whether increasing severity of RIFLE score corresponds to a lower likelihood of recovery of renal function. Some patients whose elevation in creatinine qualifies them for AKI according to the RIFLE definition have a return to baseline on hospital discharge, whereas in others creatine levels remain slightly elevated. It is unclear whether those who only partially recover from their episode of AKI have worse long-term outcomes than do patients with complete recovery, a question that merits further study. The urine output criteria, which also can be used to calculate the RIFLE class (see Table 1), pose another difficulty with using the RIFLE system during retrospective analysis inasmuch as these data are not readily available. Future prospective studies that use the RIFLE system will be able to identify patients who meet the urine output criteria for improved RIFLE classification, as well as to identify patients with temporary (L loss) or permanent (E end stage) requirements for RRT.

In summary, we found the RIFLE criteria to be a useful classification system for renal failure in patients undergoing DHCA for aortic arch surgery. Future clinical trials designed to study renal protective interventions in aortic surgery should incorporate the RIFLE criteria.

	Footnotes

 
The RIFLE criteria, an international definition for AKI, were used in a retrospective study of patients undergoing aortic surgery. Predictors for AKI were hypertension, CKD, pRBCs greater than 5 units, and a higher than predicted admission creatinine; predictors for mortality were age, AKI by RIFLE, and CVA.

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