ATS
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Ann Thorac Surg 2011;92:1539-1547. doi:10.1016/j.athoracsur.2011.04.123
© 2011 The Society of Thoracic Surgeons
This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to Personal Folders
Right arrow Download to citation manager
Right arrow Permission Requests
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Mariscalco, G.
Right arrow Articles by Sala, A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Mariscalco, G.
Right arrow Articles by Sala, A.
Related Collections
Right arrow Cardiac - other

Review

Acute Kidney Injury: A Relevant Complication After Cardiac Surgery

Giovanni Mariscalco, MD, PhDa,*, Roberto Lorusso, MD, PhDb, Carmelo Dominici, MDa, Attilio Renzulli, MD, PhDc, Andrea Sala, MDa

a Department of Surgical Sciences, Cardiac Surgery Unit, Varese University Hospital, University of Insubria, Varese, Italy
b Cardiac Surgery Unit, Civic Hospital, Brescia, Italy
c Cardiac Surgery Unit, Magna Graecia, University of Catanzaro, Catanzaro, Italy

* Address correspondence to Dr Mariscalco, Department of Surgical Sciences, Cardiac Surgery Unit, Varese University Hospital, University of Insubria, Via Guicciardini 7, Varese 21100, Italy (Email: giovannimariscalco{at}yahoo.it).


   Abstract
Top
 Abstract
Introduction
 Pathology
 Pathogenesis
 Risk Factors
 AKI Predictive Clinical Scores
 Biomarkers for the Detection...
 Strategies to Prevent AKI
 Costs and Outcomes
 Conclusions
 References
 
Acute kidney injury (AKI) occurs in as many as 40% of patients after cardiac surgery and requires dialysis in 1% of cases. Acute kidney injury is associated with an increased risk of mortality and morbidity, predisposes patients to a longer hospitalization, requires additional treatments, and increases the hospital costs. Acute kidney injury is characterized by a progressive worsening course, being the consequence of an interplay of different pathophysiologic mechanisms, with patient-related factors and cardiopulmonary bypass as major causes. Recently, several novel biomarkers have emerged, showing reasonable sensitivity and specificity for AKI prediction and protection. The development and implementation of potentially protective therapies for AKI remains essential, especially for the relevant impact of AKI on early and late survival.


   Introduction
Top
 Abstract
 Introduction
Pathology
 Pathogenesis
 Risk Factors
 AKI Predictive Clinical Scores
 Biomarkers for the Detection...
 Strategies to Prevent AKI
 Costs and Outcomes
 Conclusions
 References
 
Despite ongoing efforts to decrease its occurrence, acute kidney injury (AKI) remains a frequent complication of cardiac surgery [1–15]. Its incidence varies depending on the adopted definitions, the mode of detection, and the clinical profile of the analyzed patients [1–15]. Therefore, the incidence of AKI is different across studies, occurring in 1% to 30% of the patients when defined broadly, whereas frequency of AKI requiring dialysis is generally lower, ranging between less than 1% and 6% [1–15]. The incidence of AKI is certainly influenced by the type of cardiac operation [1–4, 6]. Typically, patients undergoing coronary artery bypass graft surgery (CABG) present the lowest incidence (2% to 5%), whereas patients undergoing valvular or combined procedures show a higher rate (as high as 30%) [16]. Similarly, AKI after transcatheter aortic valve implantation is registered in approximately 10% of the patients, whereas after complex operations such as aortic surgery for aneurysm repair or aortic dissection, incidences of AKI have been reported at 10% to 50% [12, 13, 17].

Several definitions of AKI have been proposed, and the adopted measurements include absolute creatinine value, absolute or percentage changes in serum creatinine (sCr) or estimated glomerular filtration values, and reduction in urine output [1–15]. Common definitions consider a 50% or greater rise in sCr from baseline, rise in sCr more than 1 mg/dL above baseline, or an increase of at least 25% with a peak greater than 2 mg/dL [3, 9, 10, 12, 13, 18, 19]. Other studies considered AKI only when a deterioration in renal function requiring postoperative dialysis is documented [1, 2, 4–6, 15].

New classification criteria have been recently proposed because of the wide variation in AKI definitions with a difficult result comparison across studies and populations [20, 21]. The RIFLE (an acronym for risk, injury, failure, loss, end-stage kidney disease) criteria and the Acute Kidney Injury Network (AKIN) criteria have emerged as diagnostic tools for monitoring the severity and progression of postoperative AKI, and for having accurately characterized the entire spectrum of postoperative renal dysfunction (Table 1) [20, 21]. The RIFLE classification defines three grades of severity (risk, injury, and failure) and two outcome classes (loss of kidney function and end-stage kidney disease) [20]. Similarly, the AKIN system defines three progressive AKI stages, without outcome classes [21]. Although both systems are valuable methods to evaluate AKI, the favorite classification has not been identified yet [22]. In addition, in both classifications AKI etiology, duration of sCr elevation, and recovery of renal dysfunction are not considered [11, 23].


View this table:
[in this window]
[in a new window]

  		Table 1 Classification Systems for Acute Kidney Injury
 
Finally, the new equation of the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) to estimate GFR has been proposed, being more accurate than the Modification of Diet in Renal Disease (MDRD) study equation, which is limited for the systematic underestimation of measured GFR at higher values [24, 25].


   Pathology
Top
 Abstract
 Introduction
 Pathology
Pathogenesis
 Risk Factors
 AKI Predictive Clinical Scores
 Biomarkers for the Detection...
 Strategies to Prevent AKI
 Costs and Outcomes
 Conclusions
 References
 
Postoperative AKI is characterized by a progressive worsening course with different phases, the early one being characterized by a vasomotor nephropathy with alterations in vasoreactivity and renal perfusion [26, 27]. The unavoidable consequence is prerenal azotemia, cellular adenosine triphosphate depletion, and oxidative injury, all leading to activation of bone-marrow derived and endothelial cells with a subsequent proinflammatory state [26, 27]. Then, inflammatory cells adhere to activated endothelium in the peritubular capillaries of the outer medulla, with medullary congestion and hypoxic injury to the proximal tubule [26, 27]. Proliferation of tubule cells and redifferentiation are subsequently followed by functional reconstitution. The typical lesion observed in a patient affected by postoperative AKI is acute tubular necrosis, with granular casts in the urine [26, 27].


   Pathogenesis
Top
 Abstract
 Introduction
 Pathology
 Pathogenesis
Risk Factors
 AKI Predictive Clinical Scores
 Biomarkers for the Detection...
 Strategies to Prevent AKI
 Costs and Outcomes
 Conclusions
 References
 
Although different studies have attempted to determine etiologic factors in its pathogenesis, postoperative AKI is the consequence of an interplay of different pathophysiologic mechanisms, with patient-related factors and cardiopulmonary bypass (CPB) as major causes (Fig 1) [14, 15, 28–41]. Kidneys are prone to ischemic damage because of their peculiar blood circulation, in which renal medulla is normally perfused at a low oxygen tension with a limited reserve; and CPB determines unavoidable alterations in blood flow by ischemia-reperfusion injury, low cardiac output, renal vasoconstriction, hemodilution, and loss of pulsatile flow during CPB [14, 15, 28–41]. All these factors lead to an oxygen supply/demand renal imbalance, with significant cellular injury [26, 27, 42].


Figure 1
View larger version (22K):
[in this window]
[in a new window]

  		Fig 1. Pathogenesis and clinical phases of acute kidney injury [15]. (ATP = adenosine triphosphate; COPD = chronic obstructive pulmonary disease; CPB = cardiopulmonary bypass; IABP = intraaortic balloon pump; POSTOP = postoperative.)

 
A correlation between AKI and CPB hypothermia has been also documented [40, 41]. The causative mechanism seems to be related to the increased metabolic demand, with the subsequent nephron damage due to low perfusion temperatures as the result of hypoperfusion of the superficial cortex that occurs during rewarming and restoration of normothermia [41]. A CPB perfusion temperature less than 27°C seems to be directly associated with AKI occurrence [40].

The CPB-induced systemic inflammatory response should be considered as one of the relevant determinants of postoperative AKI, with a final interstitial inflammation with tubular injury [42-44]. Cardiopulmonary bypass also exposes blood cells to nonphysiologic surfaces and shear forces, leading to cell lysis [45, 46]. The subsequent mechanical destruction of erythrocytes determines a release of plasma free hemoglobin into the circulation, finally causing occlusion of renal tubules with hemoglobin casts and necrosis of tubular cells [45, 46].

Finally, CPB-related embolization should be mentioned in the occurrence of AKI [29, 47]. Sreeram and colleagues [29], by transcranial Doppler ultrasonography, recorded Doppler signals and emboli counts during CABG, along with the assessment of creatinine changes. Emboli counts were independently associated with postoperative AKI [29].


   Risk Factors
Top
 Abstract
 Introduction
 Pathology
 Pathogenesis
 Risk Factors
AKI Predictive Clinical Scores
 Biomarkers for the Detection...
 Strategies to Prevent AKI
 Costs and Outcomes
 Conclusions
 References
 
Several studies have identified risk factors associated with AKI, and Table 2 depicts the most important ones. Type of surgery, sex, congestive heart failure, preoperative intraaortic balloon pump, anemia, diabetes mellitus, emergency status, preoperative drugs, blood transfusions, and basal renal function have been repeatedly observed [15]. In particular, preoperative renal function expressed as preoperative sCr or estimated glomerular filtration rate (eGFR) is a strong predictor of postoperative AKI [2, 3, 5, 7, 8]. Patients with a baseline creatinine level from to 2 mg/dL to 4 mg/dL are at risk for AKI, requiring dialysis in 10% to 20% of cases; patients with a preoperative creatinine level greater than 4 mg/dL are affected in approximately 30% of cases [3, 11, 47, 74, 75].


View this table:
[in this window]
[in a new window]

  		Table 2 Published Clinical Series With Reference to Acute Kidney Injury Requiring Dialysis and Acute Kidney Injury Incidence and Independent Predictors
 
Preoperative anemia contributes to kidney injury by reducing renal oxygen renal delivery, worsening oxidative stress, and impairing hemostasis [3, 48]. It impairs renal medulla, where the normal partial pressure of oxygen in the renal tissue is very low [48]. The effects of diabetes mellitus on postoperative renal failure may be the result of renal parenchymal disease, such as glomerulonephritis [15]. Nephrotoxic medications or intravenous contrast may also lead to tubular damage, with subsequent AKI [49, 50]. Angiotensin-converting enzyme inhibitors seem to be associated with postoperative renal dysfunction, although controversial data exist [19, 50]. Emergency status, congestive heart failure, and preoperative intraaortic balloon pump are AKI predictors because of the consequent reduced renal perfusion [10]. However, the predominant AKI risk factors remains CPB use, with its unavoidable alterations [14, 15, 28–41]. In this setting, patients undergoing valvular or combined procedures present a twofold or threefold risk of having postoperative renal dysfunction, mainly due to the prolonged CPB time, with the related inflammatory, hemodynamic, and embolic phenomena [28, 29]. An individual genetic AKI susceptibility has also been proposed [51–53].


   AKI Predictive Clinical Scores
Top
 Abstract
 Introduction
 Pathology
 Pathogenesis
 Risk Factors
 AKI Predictive Clinical Scores
Biomarkers for the Detection...
 Strategies to Prevent AKI
 Costs and Outcomes
 Conclusions
 References
 
Recognition of AKI risk factors is relevant. A common approach in previous studies looked for preoperative means of stratification to enable novel preventive therapeutic and renoprotective strategies [1, 4–8]. Subsequently, different clinical scoring systems have been proposed (Table 2) [1, 2, 4, 6–8]. Chertow and colleagues [1] were among the first to developed a risk index to predict postoperative need for dialysis. Their analysis involved a large multicenter cohort of patients (n = 43,642), predominantly men, undergoing cardiac surgery from the Veterans Administration health system [1]. Similar scoring systems to identify the individual risk of AKI requiring dialysis have been proposed by other groups [4, 6–8]. Mehta and colleagues [6], enrolling 449,524 patients undergoing CABG or valve surgery at more than 600 hospitals participating in The Society of Thoracic Surgeons database, proposed a bedside risk algorithm for estimating patients' probability for dialysis after cardiac surgery. A patient-specific risk model of developing AKI was elaborated by Brown and colleagues [8], by considering the multivariable AKI predictors. However, all these proposed clinical scores are limited by the fact that AKI etiology, duration of sCr/eGFR elevation, and recovery of renal dysfunction were not investigated [1, 2, 4, 6–8].


   Biomarkers for the Detection of AKI
Top
 Abstract
 Introduction
 Pathology
 Pathogenesis
 Risk Factors
 AKI Predictive Clinical Scores
 Biomarkers for the Detection...
Strategies to Prevent AKI
 Costs and Outcomes
 Conclusions
 References
 
Conventional renal biomarkers either do not detect injury in the real-time and become abnormal many hours later in the course of injury (sCr or urea) or lack specificity (urine output) [22, 54, 55]. In response to these limitations, functional genomics and proteomics have gained popularity facilitating the detection of several earlier AKI biomarkers [22, 54]. The Assessment, Serial Evaluation, and Subsequent Sequelae of Acute Kidney Injury (ASSESS-AKI) study and the Translational Research Investigating Biomarkers Endpoints in Acute Kidney Injury (TRIBE-AKI) study are ongoing prospective cohort studies, evaluating the incremental utility of novel biomarkers—cystatin C, neutrophil gelatinase-associated lipocalin (NGAL), interleukin (IL)-6, IL-18, kidney injury molecule-1 (KIM-1), liver-type fatty acid binding protein (L-FABP), and N-acetyl-β-D-glucosaminidase (NAG)—to refine the diagnosis and prognosis of AKI [22, 54].

Neutrophil gelatinase-associated lipocalin has been investigated extensively and would appear to be one of the most promising early AKI biomarkers [56]. It measures tubular stress and is involved in the ischemic renal injury and repair process [56, 57]; and NGAL increases dramatically in response to tubular injury and precedes rises in sCr by more than 24 hours [57]. A meta-analysis of 10 studies involving 1,204 patients showed NGAL to be useful in early AKI diagnosis, with area under the curve values ranging from 0.67 to 0.87 (mean 0.78) [56]. Data from 374 prospectively enrolled children undergoing CPB and evaluating serum cystatin C demonstrated that its concentrations were significantly increased in AKI patients at 12 hours after CPB and remained elevated at 24 hours [58]. In that study, cystatin C was an earlier and more accurate AKI marker compared with conventional sCr, correlating also with severity and duration of renal dysfunction [58]. Liver-type FABP is a lipocalin participating in cellular uptake of fatty acids from plasma and promoting their intracellular metabolism [55]. Portilla and coworkers [59] observed that L-FABP increases within 4 hours after cardiac surgery, anticipating the subsequent AKI development with an accuracy of 81%. However, urine L-FABP appears to rise later than NGAL [55]. In a recent prospective study of 90 patients undergoing CPB, urinary KIM-1, NAG, and NGAL were detected [60]. The area under the curve for KIM-1 to predict AKI immediately after surgery (0.68) was higher than those for NAG and NGAL [60]. In addition, KIM-1 compared with NGAL appears to be more specific to ischemic or nephrotoxic kidney injury and is not significantly affected by chronic kidney disease or urinary tract infections [55]. Interleukin-18 has shown inconsistent results [55].


   Strategies to Prevent AKI
Top
 Abstract
 Introduction
 Pathology
 Pathogenesis
 Risk Factors
 AKI Predictive Clinical Scores
 Biomarkers for the Detection...
 Strategies to Prevent AKI
Costs and Outcomes
 Conclusions
 References
 
Several preventive strategies acting at preoperative, intraoperative, and postoperative levels have been proposed (Table 3). However, these approaches are often controversial owing to the difficulty in targeting single pathways in the complex AKI pathophysiology [61].


View this table:
[in this window]
[in a new window]

  		Table 3 Available Meta-Analyses With Reference to Pharmacologic Strategies for Preventing Acute Kidney Injury After Cardiac Surgery
 
Nephrotoxic medications or intravenous contrast may lead to tubular damage, with subsequent AKI [49]. Contrast agents cause vasoconstriction-mediated medullary ischemia and direct cytotoxicity on glomerular cells [15, 49]. Ranucci and colleagues [49] suggest that delaying cardiac surgery beyond 24 hours of exposure to contrast agent and minimizing its use have significant potential to decrease AKI.

However, the most relevant preventive strategies have been focused on deleterious effects related to CPB use, such as hemodilution and nonpulsatile flow [14, 15, 28–41]. With regard to the flow characteristics during CPB, pulsatile perfusion demonstrated superior renal protection, improving organ perfusion by reducing vasoconstrictive reflexes, optimizing oxygen consumption, and reducing acidosis [30, 38]. Presta and colleagues [30] recently demonstrated that pulsatile CPB preserves renal function better than standard linear CPB, even in elderly patients.

Poor oxygen availability to the renal medulla during CPB may deteriorate renal function, causing ischemic and inflammatory organ injury [31, 32]. Ranucci and colleagues [32] observed that the lowest hematocrit and oxygen delivery are independent AKI predictors at the cut-off value of hematocrit less than 26% and oxygen delivery less than 272 mL · min–1 · m–2, respectively. The detrimental hemodilution effects may be consequently reduced by increasing oxygen delivery with an adequate increase pump flow [32]. Von Heymann and coworkers [36] observed that patients perfused at a pump flow greater than 3.0 L · min–1 · m–2 are not prone to develop AKI if with a hematocrit on CPB below 20%. Although available measurements refer to cerebral flow only, CPB flow rates of 1.8 to 2.2 L · min–1 · m–2 and a mean arterial pressure above 50 to 60 mm Hg are recommended [37].

In this setting, drugs increasing renal blood flow have been extensively tested [61]. Dopamine failed to demonstrated any renoprotective effect, and it may even exacerbate renal tubular injury in the early postoperative period, whereas fenoldopam, increasing renal blood flow in a dose-dependent manner, has been repeatedly observed to reduce AKI after cardiac surgery [61–63]. Atrial and brain natriuretic peptide and urodilatin improve natriuresis by increasing GFR as well by inhibiting sodium reabsorption by the medullary collecting duct, and they were found to mitigate renal dysfunction [15, 61, 62, 64]. Diuretics may reduce AKI, preventing tubule obstruction and decreasing oxygen consumption [15]. However, furosemide was not demonstrated to be renoprotective, and similar negative results have been observed for mannitol [61]. Other therapeutic agents attenuating the systemic CPB inflammatory syndrome with subsequent tubular injury have been intensively investigated, but also failed to reduce renal dysfunction [42–44, 61, 62]. Statins attenuate inflammation and oxidative stress, two of the mechanism responsible for AKI, but a recent meta-analysis of 30,000 cardiac surgery patients showed that statin had no renoprotective effects [15, 65]. Inconclusive data exist for N-acetylcysteine [61, 62, 66, 67]. No role for the use of dexamethasone, aprotinin, other antiinflammatory agents, or acute renal replacement therapy in the prevention of postoperative AKI exists [61].

Finally, as most of the pathophysiologic mechanisms resulting in renal injury are related to CPB use, its theoretic elimination could reduce the spectrum of renal injury after CPB, with its undesirable effects [14, 15, 28–41]. Both observational and randomized studies have shown controversial renal effects from the use of the off-pump coronary artery bypass graft technique, and available meta-analyses also presented contradictory results (Table 3) [16, 68–73]. Wijeysundera and colleagues [69] performed a meta-analysis of 37 small randomized controlled trials and 22 risk-adjusted observational studies, together encompassing more than 290,000 subjects, and demonstrated a statistically significant AKI occurrence only in the observational studies with respect to the randomized ones (odds ratio, 0.54; 95% confidence interval, 0.39 to 0.77; versus odds ratio, 0.61; 95% confidence interval, 0.25 to 1.47).


   Costs and Outcomes
Top
 Abstract
 Introduction
 Pathology
 Pathogenesis
 Risk Factors
 AKI Predictive Clinical Scores
 Biomarkers for the Detection...
 Strategies to Prevent AKI
 Costs and Outcomes
Conclusions
 References
 
Postoperative AKI has been shown to be a harbinger of poor prognosis after cardiac surgery [1-15, 74–80]. Similarly to patients requiring dialysis, with an uniform high hospital mortality ranging from 40% to 90%, patients with small fluctuations on renal function are also characterized by reduced survival [1–3, 6–8, 10, 14, 74–80]. Thakar and colleagues [74] reported a detailed continuous relationship between percent change in postoperative GFR and the risk of hospital mortality (Fig 2). In particular, they registered a 5.9% mortality rate for patients who had a 30% or greater decline in postoperative GFR and 0.4% for subjects with less than 30% decline. Patients affected by AKI requiring dialysis demonstrated a mortality rate of 54% [74].


Figure 2
View larger version (33K):
[in this window]
[in a new window]

  		Fig 2. Continuous relationship between postoperative renal dysfunction and mortality risk: preoperative glomerular filtration rate (GFR) 30 mL · min–1 · 1.73m–2 (dotted line), 60 mL · min–1 · 1.73m–2 (dashed line), and 90 mL · min–1 · 1.73m–2 (solid line).

(Reprinted by permission from Macmillan Publishers Ltd: Thakar CV, et al, Kidney Int 2005;67:1112–9 [74], copyright 2005.)

 
Similar to the in-hospital mortality, AKI contributes to long-term adverse outcomes [9, 11, 18, 23, 76, 77]. Hobson and colleagues [13] were the first to detailed the association between long-term mortality and AKI defined by RIFLE criteria. The proportion of survivors was 89% and 95% at 1 year and 44% and 63% at 10 years for patients affected by AKI and patients without it, respectively [13]. Considering the RIFLE classification, 10-year survival rates were 51%, 42%, and 26% for the risk, injury, and failure classes, respectively [13]. Acute kidney injury independently predicted long-term mortality (hazard ratio [HR] 1.39, 95% confidence interval: 1.23 to 1.57) [13]. In this setting, postoperative eGFR seems interestingly related to late survival [9, 18]. In a study of 13.593 patients undergoing isolated CABG and stratified by postoperative eGFR, those with an eGFR rate of 30 to 59 mL min–1 · 1.73m–2 had a twofold increased risk of 5-year mortality; the patients with an eGFR rate of 15 to 29 mL min–1 · 1.73m–2 or less than 15 mL · min–1 · 1.73m–2 had a fourfold to ninefold risk [18]. These data were subsequently confirmed by the Bihorac [76] and Mehta [77] studies, observing that AKI with even small changes in sCr level during hospitalization was associated with an independent long-term risk of death. In addition, recent studies documented the value of duration of AKI for predicting long-term survival [9, 11, 23]. In a cohort of nearly 5,000 cardiac surgery patients, Brown and colleagues [11] observed that long-term mortality is proportionally related to AKI duration (1 to 2 days, HR 1.66; 3 to 6 days, HR 1.94; ≥7 days, HR 3.40; Fig 3). Coca and colleagues [23] confirmed these data in a larger prospective study of more than 35,000 diabetic patients from 123 Veterans Medical Centers undergoing first noncardiac surgery. The results stress the importance of continuous monitoring of renal function to refine treatment modalities and optimize patient prognosis and follow-up. In addition, the same data draw the attention to relevant variables such as preoperative mild renal dysfunction not included in current predictive models (ie, EuroSCORE system), suggesting the need of an update to reflect changes in clinical practice [78].


Figure 3
View larger version (19K):
[in this window]
[in a new window]

  		Fig 3. Survival by duration of acute kidney injury (AKI). The proportion of patients surviving from the time of cardiac surgery is plotted by the categories for the duration of AKI: no AKI (gray line), AKI for 1 to 2 days, for 3 to 6 days, and for 7 days or more (black lines [p < 0.001 by log rank test]).

(Reprinted with permission from Brown JR et al, Ann Thorac Surg 2010;90:1142–8 [11].)

 
However, the independent association between AKI and postoperative mortality has not been clarified yet [9]. Despite attempting to account for confounding factors, it remains a distinct possibility that AKI is associated with mortality, as it occurs in patients with a severe profile of comorbidities [2–5, 9, 21]. Plausible mechanisms by which AKI after cardiac surgery is associated with mortality are different and possibly related to volume overload, dialysis catheter insertion, and impaired host immunity and infections [79, 80]. Thakar and colleagues [80], in a retrospective analysis of 24,660 patients undergoing open-heart surgery, reported a 58.5% infection rate in patients requiring dialysis compared with 23.7% for patients with AKI not requiring dialysis and 1.6% for subjects without AKI.

Inevitably, hospital costs and length of stay for patients affected by AKI are higher than for the unaffected patients, and these values increase as AKI severity worsens [2, 10, 14, 75]. Mangano and colleagues [14] first observed that intensive care unit stay and hospitalization were significantly increased among AKI patients requiring dialysis and patients who had AKI without replacement therapy compared with patients who had neither (intensive care unit stay, 14.9, 6.5, and 3.1 days, respectively; hospitalization, 28.8, 18.2, and 10.6 days, respectively). Consonant data were also observed by Chertow and colleagues [2], reporting a 3.5-day increase in hospital stay for patients affected by AKI and an increase of $8,900 in unadjusted total costs also for a small increase in sCr (≥0.3 mg/dL). In another study, patients with AKI incurred higher intensive care unit costs (1.7-fold), pharmacy (2.3-fold), and laboratory costs (1.6-fold) [75]. Patients receiving postoperative dialysis had a doubling of postoperative costs and a tripling of intensive care unit costs [75].


   Conclusions
Top
 Abstract
 Introduction
 Pathology
 Pathogenesis
 Risk Factors
 AKI Predictive Clinical Scores
 Biomarkers for the Detection...
 Strategies to Prevent AKI
 Costs and Outcomes
 Conclusions
References
 
Acute kidney injury after cardiac surgery is a vexing complication, and it is associated with an increased risk of mortality and morbidity, predisposes patients to a longer hospitalization, requires additional treatment, and increases the costs of the postoperative care. This complication is characterized by a progressively worsening course, being the consequence of an interplay of different pathophysiologic mechanisms. Hemodynamic, inflammatory, genetic, and nephrotoxic factors are all involved, leading to different AKI scoring systems and providing a framework to identify patients who are at risk and may benefit from protective strategies. In this setting, novel renal biomarkers have been identified, possibly leading to refined treatment modalities and better patient prognosis. Our understanding of how to optimally prevent and manage AKI after cardiac surgery requires an exhaustive comprehension of this complex pathogenetic framework and a great deal of additional research.


   References
Top
 Abstract
 Introduction
 Pathology
 Pathogenesis
 Risk Factors
 AKI Predictive Clinical Scores
 Biomarkers for the Detection...
 Strategies to Prevent AKI
 Costs and Outcomes
 Conclusions
 References
 

  1. Chertow GM, Lazarus JM, Christiansen CL, et al. Preoperative renal risk stratification Circulation 1997;95:878-884.[Abstract/Free Full Text]
  2. Chertow GM, Burdick E, Honour M, Bonventre JV, Bates DW. Acute kidney injury, mortality, length of stay, and costs in hospitalized patients J Am Soc Nephrol 2005;16:3365-3370.[Abstract/Free Full Text]
  3. Karkouti K, Wijeysundera DN, Yau TM, et al. Acute kidney injury after cardiac surgery: focus on modifiable risk factors Circulation 2009;119:495-502.[Abstract/Free Full Text]
  4. Wijeysundera DN, Karkouti K, Dupuis JY, et al. Derivation and validation of a simplified predictive index for renal replacement therapy after cardiac surgery JAMA 2007;297:1801-1809.[Medline]
  5. Thakar CV, Arrigain S, Worley S, Yared JP, Paganini EP. A clinical score to predict acute renal failure after cardiac surgery J Am Soc Nephrol 2005;16:162-168.[Abstract/Free Full Text]
  6. Mehta RH, Grab JD, O'Brien SM, et al. Bedside tool for predicting the risk of postoperative dialysis in patients undergoing cardiac surgery Circulation 2006;114:2208-2216.[Abstract/Free Full Text]
  7. Palomba H, de Castro I, Neto AL, Lage S, Yu L. Acute kidney injury prediction following elective cardiac surgery: AKICS score Kidney Int 2007;72:624-631.[Medline]
  8. Brown JR, Cochran RP, Leavitt BJ, et al. Multivariable prediction of renal insufficiency developing after cardiac surgery Circulation 2007;116:I139-I143.[Medline]
  9. Coca SG, Yusuf B, Shlipak MG, Garg AX, Parikh CR. Long-term risk of mortality and other adverse outcomes after acute kidney injury: a systematic review and meta-analysis Am J Kidney Dis 2009;53:961-973.[Medline]
  10. Aronson S, Fontes ML, Miao Y, Mangano DT. Risk index for perioperative renal dysfunction/failure: critical dependence on pulse pressure hypertension Circulation 2007;115:733-742.[Abstract/Free Full Text]
  11. Brown JR, Kramer RS, Coca SG, Parikh CR. Duration of acute kidney injury impacts long-term survival after cardiac surgery Ann Thorac Surg 2010;90:1142-1148.[Abstract/Free Full Text]
  12. Arnaoutakis GJ, Bihorac A, Martin TD, et al. RIFLE criteria for acute kidney injury in aortic arch surgery J Thorac Cardiovasc Surg 2007;134:1554-1560.[Abstract/Free Full Text]
  13. Hobson CE, Yavas S, Segal MS, et al. Acute kidney injury is associated with increased long-term mortality after cardiothoracic surgery Circulation 2009;119:2444-2453.[Abstract/Free Full Text]
  14. 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.[Medline]
  15. Rosner MH, Okusa, MD. Acute kidney injury associated with cardiac surgery Clin J Am Soc Nephrol 2006;1:19-32.[Abstract/Free Full Text]
  16. Seabra VF, Alobaidi S, Balk EM, Poon AH, Jaber BL. Off-pump coronary artery bypass surgery and acute kidney injury: a meta-analysis of randomized controlled trials Clin J Am Soc Nephrol 2010;5:1734-1744.[Abstract/Free Full Text]
  17. Bagur R, Webb JG, Nietlispach F, et al. Acute kidney injury following transcatheter aortic valve implantation: predictive factors, prognostic value, and comparison with surgical aortic valve replacement Eur Heart J 2010;31:865-874.[Abstract/Free Full Text]
  18. Brown JR, Cochran RP, MacKenzie TA, et al. Long-term survival after cardiac surgery is predicted by estimated glomerular filtration rate Ann Thorac Surg 2008;86:4-11.[Abstract/Free Full Text]
  19. Benedetto U, Sciarretta S, Roscitano A, et al. Preoperative angiotensin-converting enzyme inhibitors and acute kidney injury after coronary artery bypass grafting Ann Thorac Surg 2008;86:1160-1165.[Abstract/Free Full Text]
  20. Bellomo R, Ronco C, Kellum JA, Mehta RL, Palevsky P. Acute renal failure—definition, outcome measures, animal models, fluid therapy and information technology needs: the Second International Consensus Conference of the Acute Dialysis Quality Initiative (ADQI) Group Crit Care 2004;8:R204-R212.[Medline]
  21. Mehta RL, Kellum JA, Shah SV, et al. Acute Kidney Injury Network: report of an initiative to improve outcomes in acute kidney injury Crit Care 2007;11:R31.[Medline]
  22. Go AS, Parikh CR, Ikizler TA, et al. The Assessment, Serial Evaluation, and Subsequent Sequelae of Acute Kidney Injury (ASSESS-AKI) study: design and methods BMC Nephrol 2010;11:22.[Medline]
  23. Coca SG, King JT, Rosenthal RA, Perkal MF, Parikh CR. The duration of postoperative acute kidney injury is an additional parameter predicting long-term survival in diabetic veterans Kidney Int 2010;78:926-933.[Medline]
  24. Levey AS, Stevens LA, Schmid CH, et al. A new equation to estimate glomerular filtration rate Ann Intern Med 2009;150:604-612.[Medline]
  25. Stevens LA, Coresh J, Feldman HI, et al. Evaluation of the modification of diet in renal disease study equation in a large diverse population J Am Soc Nephrol 2007;18:2749-2757.[Abstract/Free Full Text]
  26. Sutton TA, Fisher CJ, Molitoris BA. Microvascular endothelial injury and dysfunction during ischemic acute renal failure Kidney Int 2002;62:1539-1549.[Medline]
  27. Okusa MD. The inflammatory cascade in acute ischemic renal failure Nephron 2002;90:133-138.[Medline]
  28. Boldt J, Brenner T, Lehmann A, Suttner SW, Kumle B, Isgro F. Is kidney function altered by the duration of cardiopulmonary bypass? Ann Thorac Surg 2003;75:906-912.[Abstract/Free Full Text]
  29. Sreeram GM, Grocott HP, White WD, Newman MF, Stafford-Smith M. Transcranial Doppler emboli count predicts rise in creatinine after coronary artery bypass graft surgery J Cardiothorac Vasc Anesth 2004;18:548-551.[Medline]
  30. Presta P, Onorati F, Fuiano L, et al. Can pulsatile cardiopulmonary bypass prevent perioperative renal dysfunction during myocardial revascularization in elderly patients? Nephron Clin Pract 2009;111:c229-c235.[Medline]
  31. Ranucci M, Pavesi M, Mazza E, et al. Risk factors for renal dysfunction after coronary surgery: the role of cardiopulmonary bypass technique Perfusion 1994;9:319-326.[Abstract/Free Full Text]
  32. Ranucci M, Romitti F, Isgro G, et al. Oxygen delivery during cardiopulmonary bypass and acute renal failure after coronary operations Ann Thorac Surg 2005;80:2213-2220.[Abstract/Free Full Text]
  33. Karkouti K, Beattie WS, Wijeysundera DN, et al. Hemodilution during cardiopulmonary bypass is an independent risk factor for acute renal failure in adult cardiac surgery J Thorac Cardiovasc Surg 2005;129:391-400.[Abstract/Free Full Text]
  34. Habib RH, Zacharias A, Schwann TA, Riordan CJ, Durham SJ, Shah A. Adverse effects of low hematocrit during cardiopulmonary bypass in the adult: should current practice be changed? J Thorac Cardiovasc Surg 2003;125:1438-1450.[Abstract/Free Full Text]
  35. Swaminathan M, Phillips-Bute BG, Conlon PJ, Smith PK, Newman MF, Stafford-Smith M. The association of lowest hematocrit during cardiopulmonary bypass with acute renal injury after coronary artery bypass surgery Ann Thorac Surg 2003;76:784-791.[Abstract/Free Full Text]
  36. von Heymann C, Sander M, Foer A, et al. The impact of an hematocrit of 20% during normothermic cardiopulmonary bypass for elective low risk coronary artery bypass graft surgery on oxygen delivery and clinical outcome—a randomized controlled study Crit Care 2006;10:R58.[Medline]
  37. Rudy LW, Heymann MA, Edmunds LH. Distribution of systemic blood flow during cardiopulmonary bypass J Appl Physiol 1973;34:194-200.[Free Full Text]
  38. Mukherjee ND, Beran AV, Hirai J, et al. In vivo determination of renal tissue oxygenation during pulsatile and nonpulsatile left heart bypass Ann Thorac Surg 1973;15:354-363.[Abstract/Free Full Text]
  39. Hornick P, Taylor K. Pulsatile and nonpulsatile perfusion: the continuing controversy J Cardiothorac Vasc Anesth 1997;11:310-315.[Medline]
  40. Boodhwani M, Rubens FD, Wozny D, Nathan HJ. Effects of mild hypothermia and rewarming on renal function after coronary artery bypass grafting Ann Thorac Surg 2009;87:489-495.[Abstract/Free Full Text]
  41. Pathi VL, Morrison J, MacPhaden A, Martin W, McQuiston AM, Wheatley DJ. Alterations in renal microcirculation during cardiopulmonary bypass Ann Thorac Surg 1998;65:993-998.[Abstract/Free Full Text]
  42. Sheridan AM, Bonventre JV. Cell biology and molecular mechanisms of injury in ischemic acute renal failure Curr Opin Nephrol Hypertens 2000;9:427-434.[Medline]
  43. Paparella D, Yau TM, Young E. Cardiopulmonary bypass induced inflammation: pathophysiology and treatment. An update. Eur J Cardiothorac Surg 2002;21:232-244.[Abstract/Free Full Text]
  44. Donnahoo KK, Meng X, Ayala A, Cain MP, Harken AH, Meldrum DR. Early kidney TNF-alpha expression mediates neutrophil infiltration and injury after renal ischemia-reperfusion Am J Physiol 1999;277:R922-R929.[Medline]
  45. Valeri CR, MacGregor H, Ragno G, Healey N, Fonger J, Khuri SF. Effects of centrifugal and roller pumps on survival of autologous red cells in cardiopulmonary bypass surgery Perfusion 2006;21:291-296.[Abstract/Free Full Text]
  46. Moussavian MR, Slotta JE, Kollmar O, Menger, MD, Schilling MK, Gronow G. Hemoglobin induces cytotoxic damage of glycine-preserved renal tubules Transpl Int 2007;20:884-894.[Medline]
  47. Blauth CI. Macroemboli and microemboli during cardiopulmonary bypass Ann Thorac Surg 1995;59:1300-1303.[Abstract/Free Full Text]
  48. De Santo L, Romano G, Della Corte A, et al. Preoperative anemia in patients undergoing coronary artery bypass grafting predicts acute kidney injury J Thorac Cardiovasc Surg 2009;138:965-970.[Abstract/Free Full Text]
  49. Ranucci M, Ballotta A, Kunkl A, et al. Influence of the timing of cardiac catheterization and the amount of contrast media on acute renal failure after cardiac surgery Am J Cardiol 2008;101:1112-1118.[Medline]
  50. Bakris GL, Weir MR. Angiotensin-converting enzyme inhibitor-associated elevations in serum creatinine: is this a cause for concern? Arch Intern Med 2000;160:685-693.[Medline]
  51. Hudson C, Hudson J, Swaminathan M, Shaw A, Stafford-Smith M, Patel UD. Emerging concepts in acute kidney injury following cardiac surgery Semin Cardiothorac Vasc Anesth 2008;12:320-330.[Abstract/Free Full Text]
  52. Brull DJ, Montgomery HE, Sanders J, et al. Interleukin-6 gene -174g>c and -572g>c promoter polymorphisms are strong predictors of plasma interleukin-6 levels after coronary artery bypass surgery Arterioscler Thromb Vasc Biol 2001;21:1458-1463.[Abstract/Free Full Text]
  53. Popov AF, Schulz EG, Schmitto JD, et al. Relation between renal dysfunction requiring renal replacement therapy and promoter polymorphism of the erythropoietin gene in cardiac surgery Artif Organs 2010;34:961-968.[Medline]
  54. Lu JC, Coca SG, Patel UD, Cantley L, Parikh CR. Searching for genes that matter in acute kidney injury: a systematic review Clin J Am Soc Nephrol 2009;4:1020-1031.[Abstract/Free Full Text]
  55. Moore E, Bellomo R, Nichol A. Biomarkers of acute kidney injury in anesthesia, intensive care and major surgery: from the bench to clinical research to clinical practice. Minerva Anestesiol;76:425-40.
  56. Haase M, Bellomo R, Devarajan P, Schlattmann P, Haase-Fielitz A. Accuracy of neutrophil gelatinase-associated lipocalin (NGAL) in diagnosis and prognosis in acute kidney injury: a systematic review and meta-analysis Am J Kidney Dis 2009;54:1012-1024.[Medline]
  57. Schmidt-Ott KM, Mori K, Kalandadze A, et al. Neutrophil gelatinase-associated lipocalin-mediated iron traffic in kidney epithelia Curr Opin Nephrol Hypertens 2006;15:442-449.[Medline]
  58. Krawczeski CD, Vandevoorde RG, Kathman T, et al. Serum cystatin C is an early predictive biomarker of acute kidney injury after pediatric cardiopulmonary bypass. Clin J Am Soc Nephrol;5:1552-7.
  59. Portilla D, Dent C, Sugaya T, et al. Liver fatty acid-binding protein as a biomarker of acute kidney injury after cardiac surgery Kidney Int 2008;73:465-472.[Medline]
  60. Han WK, Wagener G, Zhu Y, Wang S, Lee HT. Urinary biomarkers in the early detection of acute kidney injury after cardiac surgery Clin J Am Soc Nephrol 2009;4:873-882.[Abstract/Free Full Text]
  61. Park M, Coca SG, Nigwekar SU, Garg AX, Garwood S, Parikh CR. Prevention and treatment of acute kidney injury in patients undergoing cardiac surgery: a systematic review Am J Nephrol 2010;31:408-418.[Medline]
  62. Patel NN, Rogers CA, Angelini GD, Murphy GJ. Pharmacological therapies for the prevention of acute kidney injury following cardiac surgery: a systematic review Heart Fail Rev 2011 March 13[E-Pub ahead of print].
  63. Nigwekar SU, Navaneethan SD, Parikh CR, Hox JK. Atrial Natriuretic peptide for management of acute kidney injury: a systematic review and meta-analysis Clin J Am Soc Nephrol 2009;4:261-272.[Abstract/Free Full Text]
  64. Landoni G, Biondi-Zoccai GG, Marino G, et al. Fenoldopam reduces the need for renal replacement therapy and in-hospital death in cardiovascular surgery: a meta-analysis J Cardiothorac Vasc Anesth 2008;22:27-33.[Medline]
  65. Liakopoulos OJ, Choi YH, Haldenwang PL, et al. Impact of preoperative statin therapy on adverse postoperative outcomes in patients undergoing cardiac surgery: a meta-analysis of over 30,000 patients Eur Heart J 2008;29:1548-1559.[Abstract/Free Full Text]
  66. Nigwekar SU, Kandula P. N-acetylcysteine in cardiovascular-surgery-associated renal failure: a meta-analysis Ann Thorac Surg 2009;87:139-147.[Abstract/Free Full Text]
  67. Adabag AS, Ishani A, Bloomfield HE, Ngo AK, Wilt TJ. Efficacy of N-acetylcysteine in preventing renal injury after heart surgery: a systematic review of randomized trials Eur Heart J 2009;30:1910-1917.[Abstract/Free Full Text]
  68. Nigwekar SU, Kandula P, Hix JK, Thakar CV. Off-pump coronary artery bypass surgery and acute kidney injury: a meta-analysis of randomized and observational studies Am J Kidney Dis 2009;54:413-423.[Medline]
  69. Wijeysundera DN, Beattie WS, Djaiani G, et al. Off-pump coronary artery surgery for reducing mortality and morbidity: meta-analysis of randomized and observational studies J Am Coll Cardiol 2005;46:872-882.[Medline]
  70. Reston JT, Tregear SJ, Turkelson CM. Meta-analysis of short-term and mid-term outcomes following off-pump coronary artery bypass grafting Ann Thorac Surg 2003;76:1510-1515.[Abstract/Free Full Text]
  71. Cheng DC, Bainbridge D, Martin JE, Novick RJ. Does off-pump coronary artery bypass reduce mortality, morbidity, and resource utilization when compared with conventional coronary artery bypass?. A meta-analysis of randomized trials. Anesthesiology 2005;102:188-203.[Medline]
  72. Sedrakyan A, Wu AW, Parashar A, Bass EB, Treasure T. Off-pump surgery is associated with reduced occurrence of stroke and other morbidity as compared with traditional coronary artery bypass grafting: a meta-analysis of systematically reviewed trials Stroke 2006;37:2759-2769.[Free Full Text]
  73. Kuss O, von Salviati B, Borgermann J. Off-pump versus on-pump coronary artery bypass grafting. A systematic review and meta-analysis of propensity score analyses. J Thorac Cardiovasc Surg 2010;140:829-835.[Abstract/Free Full Text]
  74. Thakar CV, Worley S, Arrigain S, Yared JP, Paganini EP. Influence of renal dysfunction on mortality after cardiac surgery: modifying effect of preoperative renal function Kidney Int 2005;67:1112-1119.[Medline]
  75. Dasta JF, Kane-Gill SL, Durtschi AJ, Pathak DS, Kellum JA. Costs and outcomes of acute kidney injury (AKI) following cardiac surgery Nephrol Dial Transplant 2008;23:1970-1974.[Abstract/Free Full Text]
  76. Bihorac A, Yavas S, Subbiah S, et al. Long-term risk of mortality and acute kidney injury during hospitalization after major surgery Ann Surg 2009;249:851-858.[Medline]
  77. Mehta RH, Honeycutt E, Patel UD, et al. Impact of recovery of renal function on long-term mortality after coronary artery bypass grafting Am J Cardiol 2010;106:1728-1734.[Medline]
  78. Miceli A, Bruno VD, Capoun R, et al. Mild renal dysfunction in patients undergoing cardiac surgery as a new risk factor for EuroSCORE Heart 2011;97:362-365.[Abstract/Free Full Text]
  79. Hoste EA, De Waele JJ. Physiologic consequences of acute renal failure on the critically ill Crit Care Clin 2005;21:251-260.[Medline]
  80. Thakar CV, Yared JP, Worley S, Cotman K, Paganini EP. Renal dysfunction and serious infections after open-heart surgery Kidney Int 2003;64:239-246.[Medline]



This article has been cited by other articles:


Home page
 Circ Heart FailHome page
D. Olsson, U. Sartipy, F. Braunschweig, and M. J. Holzmann
Acute Kidney Injury Following Coronary Artery Bypass Surgery and Long-term Risk of Heart Failure
Circ Heart Fail, January 1, 2013; 6(1): 83 - 90.
[Abstract] [Full Text] [PDF]

Home page
 Br J AnaesthHome page
J. Martensson, C.- R. Martling, and M. Bell
Novel biomarkers of acute kidney injury and failure: clinical applicability
Br. J. Anaesth., December 1, 2012; 109(6): 843 - 850.
[Abstract] [Full Text] [PDF]

Home page
 Ann. Thorac. Surg.Home page
H.-S. Tsai, F.-C. Tsai, Y.-C. Chen, L.-S. Wu, S.-W. Chen, J.-J. Chu, P.-J. Lin, and P.-H. Chu
Impact of Acute Kidney Injury on One-Year Survival After Surgery for Aortic Dissection
Ann. Thorac. Surg., November 1, 2012; 94(5): 1407 - 1412.
[Abstract] [Full Text] [PDF]

Home page
 Ann. Thorac. Surg.Home page
G. U. Roh, J. W. Lee, S. B. Nam, J. Lee, J.-r. Choi, and Y. H. Shim
Incidence and Risk Factors of Acute Kidney Injury After Thoracic Aortic Surgery for Acute Dissection
Ann. Thorac. Surg., September 1, 2012; 94(3): 766 - 771.
[Abstract] [Full Text] [PDF]

Home page
 Ann. Thorac. Surg.Home page
G. Mariscalco, C. Dominici, and C. Beghi
Reply.
Ann. Thorac. Surg., May 1, 2012; 93(5): 1764 - 1764.
[Full Text] [PDF]

Home page
 Ann. Thorac. Surg.Home page
O. Tutarel and J. T. Kielstein
Symmetrical Dimethylarginine as a Biomarker for Acute Kidney Injury
Ann. Thorac. Surg., May 1, 2012; 93(5): 1763 - 1764.
[Full Text] [PDF]

Home page
 BMJ OpenHome page
A. X. Garg, P. J. Devereaux, S. Yusuf, M. S. Cuerden, C. R. Parikh, S. G. Coca, M. Walsh, R. J. Cook, R. P. Whitlock, N. Noiseux, et al.
Coronary Artery Bypass Grafting Surgery Off- or On-pump Revascularisation Study (CORONARY): kidney substudy analytic protocol of an international randomised controlled trial
BMJ Open, April 18, 2012; 2(2): e001080 - e001080.
[Abstract] [Full Text] [PDF]

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to Personal Folders
Right arrow Download to citation manager
Right arrow Permission Requests
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Mariscalco, G.
Right arrow Articles by Sala, A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Mariscalco, G.
Right arrow Articles by Sala, A.
Related Collections
Right arrow Cardiac - other

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
ANN THORAC SURG ASIAN CARDIOVASC THORAC ANN EUR J CARDIOTHORAC SURG
J THORAC CARDIOVASC SURG ICVTS ALL CTSNet JOURNALS