Abstract
Purpose
Acute kidney injury (AKI) is a potentially serious complication of cardiac surgery. Anemia and red blood cell (RBC) transfusion have individually been identified as potentially modifiable risk factors, but their interrelationship with AKI has not been clearly defined. The purpose of this study was to explore the interrelationship of preoperative anemia, intraoperative anemia, and RBC transfusion on the day of surgery with AKI in cardiac surgery.
Methods
This historical cohort study included 16 hospitals, each contributing data on approximately 100 consecutive patients who underwent cardiac surgery with cardiopulmonary bypass. Acute kidney injury was defined as a > 50% increase in creatinine levels during the first postoperative week. Multivariable regression was used to identify the interrelationship between preoperative anemia (hemoglobin < 130 g·L−1 in males and < 120 g·L−1 in females), intraoperative anemia (hemoglobin < 80 g·L−1 during cardiopulmonary bypass), RBC transfusion on the day of surgery, and their interaction terms, after adjusting for site and baseline AKI risk.
Results
Of the 1,444 patients included in the study, 541 (37%) had preoperative anemia, 501 (35%) developed intraoperative anemia, 619 (43%) received RBC transfusions, and 238 (16%) developed AKI. After risk-adjustment, an individual with the combination of these three risk factors had a 2.6-fold (95% confidence interval 2.0 to 3.3) increase in the relative risk of AKI over an individual with none of these risk factors.
Conclusions
Preoperative anemia, intraoperative anemia, and RBC transfusion on the day of surgery are interrelated risk factors for AKI after cardiac surgery. Targeting these risk factors may reduce the burden of AKI.
Résumé
Objectif
La lésion rénale aiguë (LRA) est une complication potentiellement grave de la chirurgie cardiaque. L’anémie et la transfusion de globules rouges ont individuellement été identifiées comme étant des facteurs de risque potentiellement modifiables, mais la relation entre ces facteurs et la LRA n’a pas été clairement établie. Le but de cette étude était d’explorer la relation entre l’anémie préopératoire, l’anémie peropératoire et la transfusion de globules rouges le jour de l’intervention avec la LRA en chirurgie cardiaque.
Méthodes
Cette étude de cohorte historique a inclus 16 hôpitaux, chacun procurant les données d’environ 100 patients consécutifs ayant subi une chirurgie cardiaque avec circulation extracorporelle. La lésion rénale aiguë a été définie par une augmentation du taux de créatinine > 50 % au cours de la première semaine postopératoire. Une analyse en régression multifactorielle a servi à identifier les rapports entre l’anémie préopératoire (hémoglobine < 130 g·L−1 chez l’homme et < 120 g·L−1 chez la femme), l’anémie peropératoire (hémoglobine < 80 g·L−1 pendant la circulation extracorporelle), la transfusion de globules rouges le jour de la chirurgie et leurs interactions, après ajustement pour le site et le risque de base de la LRA.
Résultats
Sur les 1 444 patients inclus dans l’étude, 541 (37 %) avaient une anémie préopératoire, 501 (35 %) ont développé une anémie peropératoire, 619 (43 %) ont reçu des transfusions de globules rouges et 238 (16 %) ont développé une LRA. Après ajustement pour le risque, la combinaison de ces trois facteurs de risque chez un même individu était associée à une augmentation du risque relatif de la LRA par un facteur de 2,6 (intervalle de confiance à 95 %: 2,0 à 3,3) par rapport à un individu n’ayant aucun de ces facteurs de risque.
Conclusions
L’anémie préopératoire, l’anémie peropératoire et la transfusion de globules rouges le jour de la chirurgie sont des facteurs de risque inter relié de la LRA après chirurgie cardiaque. La morbidité de la LRA pourrait possiblement être réduite en ciblant ces facteurs de risque.
Similar content being viewed by others
Avoid common mistakes on your manuscript.
Acute kidney injury (AKI) is a prevalent and prognostically important complication of cardiac surgery, occurring in up to 30% of patients and substantially increasing short- and long-term morbidity and mortality.1 – 5 As there are currently no clinically proven therapies that can prevent or treat AKI in cardiac surgery,1 the best means for reducing the burden of AKI may be through risk factor modification.
Several risk factors for AKI have been identified.6 While most are not modifiable, anemia and red blood cell (RBC) transfusion have been identified as potentially modifiable risk factors.2 , 6 They may therefore be ideal targets for reducing the burden of AKI in cardiac surgery. Importantly, these risk factors are interrelated, and while several studies have explored their individual relationship with AKI, the effect of their interrelationship with AKI has not been clearly defined. Existing evidence suggests that this effect may be synergistic, such that anemic patients may be more susceptible to the deleterious effects of RBC transfusions on the kidney than non-anemic patients.7 – 9 This interrelationship, if proven valid, could have important clinical implications for risk management and patient optimization.10 , 11 The objective of this study was to explore the interrelationship of preoperative anemia, intraoperative anemia, and RBC transfusion on the day of surgery with AKI in cardiac surgery.
Methods
Study setting, patient sample, and data collection
Seventeen university-affiliated hospitals in Canada, United States, Australia, and New Zealand participated in this retrospective observational study. After obtaining institutional Research Ethics Board approval at the University Health Network (REB 11-0663-AE; initial approval Sept 2011) and at all participating centres, investigators at each hospital retrospectively collected data on 100 consecutive adult (> 18 yr) patients who underwent cardiac surgery with cardiopulmonary bypass (CPB) from January 1, 2010 to December 31, 2011. Cases involving heart transplantation, ventricular assist device placement, or repair of complex congenital abnormalities were excluded because these procedures were not performed at all participating hospitals. Patients were also excluded if they were dialysis-dependent before surgery, had no creatinine or hemoglobin measures before surgery, had no record of timing of perioperative transfusions, or had no creatinine measures after surgery. Based on previous experience,2 we anticipated that the number of patients obtained from the participating hospitals would include sufficient cases of AKI to allow us to identify the relationships of interest by multivariable analysis.
Using standardized case report forms, detailed perioperative data (including demographics, laboratory tests, medications used, nature of surgery, blood product transfusions on the day of or day after surgery, and major in-hospital postoperative complications) were collected from existing clinical databases and hospital charts. Data were entered into a computerized database with validity checks. All queries were resolved by referring to the patients’ original records.
Primary independent variables
The primary variables of interest were preoperative anemia, defined as a hemoglobin concentration < 130 g·L−1 in males and < 120 g·L−1 in females,12 intraoperative anemia, defined as hemoglobin < 80 g·L−1 during CPB,8 and RBC transfusion on the day of surgery.
Dependent variable
Patients with a > 50% increase in serum creatinine at any time during the first week after surgery were categorized as having had AKI. This creatinine threshold is consistent with current definitions of AKI.13
Statistical analyses
SAS™ version 9.3 (SAS Institute, Inc., Cary, NC, USA) was used for the statistical analyses. Categorical variables were summarized as frequency (percentage) and continuous variables as median [interquartile range] unless otherwise stated. Variability in the incidences of anemia and RBC transfusions across sites was assessed by comparing a logistic regression model, which included each site as a factor, with the null model (intercept only) using a likelihood ratio test.
The unadjusted relationship of preoperative anemia, intraoperative anemia, and RBC transfusion on the day of surgery with AKI was assessed by univariate Poisson regression with robust error variance.14 Multivariable Poisson regression was used for determining the independent relationships of these three variables as well as their two-way and three-way interaction terms with AKI, after accounting for overdispersion15 and controlling for the underlying risk of AKI using the Cleveland risk score (Table 1).16 , 17 Site was also included as a categorical variable to account for unmeasured case-mix differences. Interaction terms that were not statistically significant (P > 0.2) were removed and the model was reconstructed. Seventeen of the 1,444 patients in the study had missing variables and were excluded from these analyses, leaving 1,427 patients. The effect of clustering (within-site correlation) was evaluated by constructing the model with generalized estimating equations.18
Bootstrap resampling was used for internal validation. One-thousand computer-generated samples, each including 1,427 patients, were derived from the study cohort by random selection with replacement, and the model was refitted for each sample. The mean and standard deviation bootstrap parameter estimates were used to assess the results of the multivariable modelling.
Results
Data from one site (n = 100) could not be used because the timing of the RBC transfusion was not recorded. An additional 139 patients met one or more of the exclusion criteria and were excluded from the analyses, leaving 1,444 patients in the study. Of these, 541 (37%) had preoperative anemia, 501 (35%) developed intraoperative anemia (13 had missing data), 619 (43%) received RBC transfusions on the day of surgery, and 238 (16%) developed AKI (37 of whom required dialysis). There was significant (P < 0.001) site variability in the incidences of all four variables (Figure). Sample characteristics are presented in Table 2. In univariable analysis, preoperative anemia, intraoperative anemia, and RBC transfusion on the day of surgery were all significantly associated with AKI, with their respective relative risks (95% confidence interval [CI]) being 1.9 (95% CI 1.5 to 2.3), 2.1 (95% CI 1.7 to 2.6), and 2.0 (95% CI 1.7 to 2.5).
In multivariable analysis, of the interaction terms analyzed, only the interaction of preoperative anemia with RBC transfusion was associated with AKI and hence was retained in the final model (Table 3); the remaining interaction terms had P values > 0.2. With the inclusion of this interaction term, neither preoperative anemia nor RBC transfusion was independently associated with AKI (Tables 3 and 4). In patients with preoperative anemia, however, RBC transfusion was associated with a 1.9-fold (95% CI 1.4 to 2.5) increase in the relative risk of AKI (Table 4). Intraoperative anemia was independently associated with a 1.4-fold (95% CI 1.1 to 1.7) increase in the relative risk of AKI. An individual with the combination of preoperative anemia, intraoperative anemia, and RBC transfusion had a 2.6-fold (95% CI 2.0 to 3.3) increase in the relative risk of AKI over an individual with none of these risk factors (Table 4). The results of bootstrap resampling were consistent with the regression modelling (Table 3).
Discussion
In this retrospective cohort study that included 1,444 patients who underwent cardiac surgery at 16 hospitals, we explored the relationship between preoperative anemia, intraoperative anemia, and RBC transfusion on the day of surgery. We found that more than one-third of patients had one or more of these risk factors and that 16% of patients developed AKI. After accounting for the underlying risk of AKI and the influence of interactions amongst the risk factors, we found that an individual with the combination of preoperative anemia, intraoperative anemia, and RBC transfusion had a 2.6-fold (95% CI 2.0 to 3.3) increase in the relative risk of AKI over an individual with none of these risk factors (Table 4).
Anemia and RBC transfusion have been observed in multiple previous studies as important risk factors for AKI after cardiac surgery, but the interrelationship between these variables and AKI has not been as extensively reported.19 , 20 In a single-centre observational study comprised of 2,113 propensity-score matched pairs of anemic and non-anemic patients who underwent cardiac surgery with CPB and received up to three units of perioperative RBC transfusions, the risk of AKI was increased in direct proportion to the number of transfusions in both groups, but the increase was much more pronounced in anemic patients.7 In non-anemic patients, the AKI rate increased from 1.7% in non-transfused patients to 3.2% in those who received three units of RBCs (P = 0.1); however, in anemic patients, the rate increased from 1.8% to 6.6% (P < 0.0001).7 In another single-centre observational study by Loor et al., which included 9,144 patients who underwent cardiac surgery with CPB, intraoperative anemia, defined as a nadir hematocrit < 25%, was independently associated with AKI but an RBC transfusion alone was not. As in our study, their reported risk of AKI was highest when both anemia and transfusion were present.8 The influence of preoperative anemia, however, was not clearly described in their study. Similar findings were reported by Ranucci et al. in their study of 1,766 adult patients who underwent isolated coronary artery bypass graft surgery.9 Overall, therefore, our findings are consistent with the existing single-centre studies described above.
The mechanisms by which perioperative anemia and RBC transfusions may cause AKI in cardiac surgery have not been elucidated. Recent proteomic studies indicate that all patients undergoing cardiac surgery with CPB develop the early stages of ischemia-reperfusion kidney injury, but whether they go on to develop AKI depends on both the occurrence of other renal insults as well as the severity of the ensuing inflammatory response, renal hypoxia, and oxidative stress.21 Anemia and RBC transfusion could cause AKI either by harming the kidney directly or by increasing patients’ susceptibility to concomitant renal insults.
During storage, RBCs undergo several changes that may harm the kidney after transfusion. These changes include a decrease in 2,3-diphosphoglycerate, adenosine triphosphate, and S-nitrosohemoglobin as well as an increase in the concentrations of lactate, potassium, cytokines, iron, and free hemoglobin in the supernatant.22 – 26 Red blood cells also become progressively less deformable and more fragile during storage in a time-dependent manner. This results in the accumulation of hemoglobin-laden microvesicles in the supernatant as well as predisposing up to 25% of RBCs to early hemolysis within one hour after transfusion.27 – 29 Cumulatively, these changes may result in post-transfusion impairment of tissue oxygen delivery and exacerbation of inflammatory response and oxidative stress, thereby harming the kidney.19 In line with this hypothesis, some (but not all) retrospective studies have found an association between age of blood and adverse outcomes.30 , 31
The contributory effects of anemia to AKI are likely also multifactorial. First, anemic patients (both preoperative and intraoperative) have lower hemoglobin concentrations throughout the perioperative period than non-anemic patients,32 predisposing them to renal hypoxia.20 Second, many anemic patients have pre-existing subclinical kidney disease that may increase renal tubular oxygen consumption and oxidative stress,33 – 35 thus increasing their susceptibility to concurrent renal insults. Finally, anemic patients have abnormal iron metabolism36 – 38 that may affect the clearance of the large amount of iron released when RBCs are hemolyzed, either during storage or soon after transfusion, and this may potentially lead to the presence of free iron and hemoglobin in the circulation.39 , 40
Our study has several limitations. Since neither the cause nor the duration of preoperative anemia were known, it is possible that diseases associated with both anemia and AKI may account for some of the observed relationships. It is also possible that the observed relationships were unduly influenced by other unmeasured confounders such as colloid use.41 Another limitation is that the number of patients in various categories of anemia and transfusion are small (Table 4), resulting in relatively wide confidence intervals for some of the coefficients (Table 3). Finally, we could not elucidate the cause of anemia, transfusions, or AKI, and we did not have data on the age of the transfused RBCs.31 Furthermore, we did not use a pre-specified protocol to guide transfusion therapy across all participating sites, and intraoperative management of blood salvage, hemodilution, and the conduct of CPB was left to the individual centres. On the other hand, our study has a number of strengths. Consecutive patients underwent surgery at multiple hospitals; the data used in our study were collected by blinded data abstractors, and the interrelationships between the variables of interest were carefully explored. Nevertheless, further studies are required to confirm or refute our findings.
The natural clinical implication of our findings is that correcting preoperative anemia and avoiding intraoperative anemia and RBC transfusion on the day of surgery could potentially reduce the burden of AKI after cardiac surgery. One relatively simple strategy is to reduce perioperative hemodilution by minimizing fluid administration and using retrograde autologous priming of the cardiopulmonary circuit.42 Transfusion practice bundles that incorporate point-of-care coagulation testing may also achieve these objectives by reducing blood loss and transfusions through better management of coagulopathy.43 , 44 Erythropoietin stimulating agents may also be used to correct preoperative anemia, thereby avoiding intraoperative anemia and RBC transfusion,42 but the risk-benefit of this intervention in cardiac surgery has not been elucidated.45
Other potential options that are currently undergoing evaluation include optimizing oxygen delivery by modifying pump flow;46 washing of blood to remove the pro-inflammatory molecules, free hemoglobin, and iron that accumulate in the supernatant during storage;47 haptoglobin therapy to scavenge the free hemoglobin that can be present after CPB and blood transfusion;48 and prophylactic RBC transfusion one to two days before surgery in patients with preoperative anemia.49 This latter approach has been postulated to “reduce the risk of AKI by reducing the severity of anemia, reducing the need for RBC transfusions, allowing time for the transfused blood to recover from the deleterious changes that they undergo during storage, and allowing time for the kidneys to recuperate from the harmful effects of transfused blood before they are exposed to other renal insults” during surgery.49 , 50 The risk-benefit profiles of these investigational interventions are yet to be determined.
In conclusion, the results of this multicentre retrospective study showed that preoperative anemia, intraoperative anemia, and RBC transfusion on the day of surgery are interrelated risk factors for AKI after cardiac surgery. Our findings suggest that preventing or correcting these risk factors may therefore reduce the burden of AKI in this setting.
References
Rosner MH, Okusa MD. Acute kidney injury associated with cardiac surgery. Clin J Am Soc Nephrol 2006; 1: 19-32.
Karkouti K, Wijeysundera DN, Yau TM, et al. Acute kidney injury after cardiac surgery: focus on modifiable risk factors. Circulation 2009; 119: 495-502.
Brown JR, Cochran RP, Dacey LJ, et al. Perioperative increases in serum creatinine are predictive of increased 90-day mortality after coronary artery bypass graft surgery. Circulation 2006; 114(1 Suppl): I409-13.
Hobson CE, Yavas S, Segal MS, et al. Acute kidney injury is associated with increased long-term mortality after cardiothoracic surgery. Circulation 2009; 119: 2444-53.
Ishani A, Nelson D, Clothier B, et al. The magnitude of acute serum creatinine increase after cardiac surgery and the risk of chronic kidney disease, progression of kidney disease, and death. Arch Intern Med 2011; 171: 226-33.
Parida S, Badhe AS. Cardiac surgery-associated acute kidney injury. J Anesth 2013; 27: 433-46.
Karkouti K, Wijeysundera DN, Yau TM, et al. Influence of erythrocyte transfusion on the risk of acute kidney injury after cardiac surgery differs in anemic and non-anemic patients. Anesthesiology 2011; 115: 523-30.
Loor G, Rajeswaran J, Li L, et al. The least of 3 evils: exposure to red blood cell transfusion, anemia, or both? J Thorac Cardiovasc Surg 2013; 146: 1480-7.e6.
Ranucci M, Biagioli B, Scolletta S, et al. Lowest hematocrit on cardiopulmonary bypass impairs the outcome in coronary surgery: an Italian Multicenter Study from the National Cardioanesthesia Database. Tex Heart Inst J 2006; 33: 300-5.
Karkouti K, Wijeysundera DN, Beattie WS, et al. Variability and predictability of large-volume red blood cell transfusion in cardiac surgery: a multicenter study. Transfusion 2007; 47: 2081-8.
Verniquet A, Kakel R. New paradigms for managing preoperative anemia. Can J Anesth 2012; 59: 230-1.
World Health Organization. Iron deficiency Anaemia: Assessment, Prevention, and Control. A Guide for Programme Managers, 2001. Available from URL: http://whqlibdoc.who.int/hq/2001/WHO_NHD_01.3.pdf (accessed November 2014).
Levey AS, Levin A, Kellum JA. Definition and classification of kidney diseases. Am J Kidney Dis 2013; 61: 686-8.
Zou G. A modified Poisson regression approach to prospective studies with binary data. Am J Epidemiol 2004; 159: 702-6.
Allison PD. Regression for count data. In: Allison PD, editor. Logistic Regression Using SAS®: Theory and Application. 2nd ed. Cary, NC: SAS Institute Inc.; 2012. p. 265-90.
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: 162-8.
Englberger L, Suri RM, Li Z, et al. Validation of clinical scores predicting severe acute kidney injury after cardiac surgery. Am J Kidney Dis 2010; 56: 623-31.
Allison PD. Logit analysis of longitudinal and other clustered data. In: Allison PD, editor. Logistic Regression Using SAS®: Theory and Application. 2nd ed. Cary, NC: SAS Institute; 2012. p. 217-64.
Karkouti K. Transfusion and risk of acute kidney injury in cardiac surgery. Br J Anaesth 2012; 109(Suppl 1): i29-38.
Hare GM, Freedman J, David MC. Review article: risks of anemia and related management strategies: can perioperative blood management improve patient safety? Can J Anesth 2013; 60: 168-75.
Ho J, Lucy M, Krokhin O, et al. Mass spectrometry-based proteomic analysis of urine in acute kidney injury following cardiopulmonary bypass: a nested case-control study. Am J Kidney Dis 2009; 53: 584-95.
Almac E, Ince C. The impact of storage on red cell function in blood transfusion. Best Pract Res Clin Anaesthesiol 2007; 21: 195-208.
Comporti M, Signorini C, Buonocore G, Ciccoli L. Iron release, oxidative stress and erythrocyte ageing. Free Radic Biol Med 2002; 32: 568-76.
Hogman CF, Meryman HT. Storage parameters affecting red blood cell survival and function after transfusion. Transfus Med Rev 1999; 13: 275-96.
Donadee C, Raat NJ, Kanias T, et al. Nitric oxide scavenging by red blood cell microparticles and cell-free hemoglobin as a mechanism for the red cell storage lesion. Circulation 2011; 124: 465-76.
Bennett-Guerrero E, Veldman TH, Doctor A, et al. Evolution of adverse changes in stored RBCs. Proc Natl Acad Sci U S A 2007; 104: 17063-8.
Bosman GJ, Werre JM, Willekens FL, Novotny VM. Erythrocyte ageing in vivo and in vitro: structural aspects and implications for transfusion. Transfus Med 2008; 18: 335-47.
Bosman GJ, Lasonder E, Groenen-Dopp YA, Willekens FL, Werre JM, Novotny VM. Comparative proteomics of erythrocyte aging in vivo and in vitro. J Proteomics 2010; 73: 396-402.
Luten M, Roerdinkholder-Stoelwinder B, Schaap NP, de Grip WJ, Bos HJ, Bosman GJ. Survival of red blood cells after transfusion: a comparison between red cells concentrates of different storage periods. Transfusion 2008; 48: 1478-85.
Zimring JC. Fresh versus old blood: are there differences and do they matter? Hematology Am Soc Hematol Educ Program 2013; 2013: 651-5.
Karkouti K. From the Journal archives: The red blood cell storage lesion: past, present, and future. Can J Anesth 2014; 61: 583-6.
Karkouti K. Wijeysundera DN, Beattie WS; Reducing Bleeding in Cardiac Surgery (RBC) Investigators. Risk associated with preoperative anemia in cardiac surgery: a multicenter cohort study. Circulation 2008; 117: 478-84.
Estrella MM, Astor BC, Kottgen A, Selvin E, Coresh J, Parekh RS. Prevalence of kidney disease in anaemia differs by GFR-estimating method: The Third National Health and Nutrition Examination Survey (1988-94). Nephrol Dial Transplant 2010; 25: 2542-8.
Schrier RW, Shapiro JI, Chan L, Harris DC. Increased nephron oxygen consumption: potential role in progression of chronic renal disease. Am J Kidney Dis 1994; 23: 176-82.
Alfrey AC. Role of iron and oxygen radicals in the progression of chronic renal failure. Am J Kidney Dis 1994; 23: 183-7.
Grune T, Sommerburg O, Siems WG. Oxidative stress in anemia. Clin Nephrol 2000; 53(1 Suppl): S18-22.
Lasocki S, Longrois D, Montravers P, Beaumont C. Hepcidin and anemia of the critically ill patient: bench to bedside. Anesthesiology 2011; 114: 688-94.
Nemeth E, Ganz T. Regulation of iron metabolism by hepcidin. Annu Rev Nutr 2006; 26: 323-42.
Hod EA, Zhang N, Sokol SA, et al. Transfusion of red blood cells after prolonged storage produces harmful effects that are mediated by iron and inflammation. Blood 2010; 115: 4284-92.
Ozment CP, Turi JL. Iron overload following red blood cell transfusion and its impact on disease severity. Biochim Biophys Acta 2009; 1790: 694-701.
Bagshaw SM, Chawla LS. Hydroxyethyl starch for fluid resuscitation in critically ill patients. Can J Anesth 2013; 60: 709-13.
Society of Thoracic Surgeons Blood Conservation Guideline Task Force; Ferraris VA, Brown JR, Despotis GJ, et al. 2011 update to the Society of Thoracic Surgeons and the Society of Cardiovascular Anesthesiologists blood conservation clinical practice guidelines. Ann Thorac Surg 2011; 2011(91): 944-82.
Weber CF, Gorlinger K, Meininger D, et al. Point-of-care testing: a prospective, randomized clinical trial of efficacy in coagulopathic cardiac surgery patients. Anesthesiology 2012; 117: 531-47.
Karkouti K, McCluskey SA, Callum J, Freedman J, Selby R, Timoumi T, Roy D, Rao V. Evaluation of a novel transfusion algorithm employing point-of-care coagulation assays in cardiac surgery: a retrospective cohort study with interrupted time-series analysis. Anesthesiology 2014. DOI:10.1097/ALN.0000000000000556.
Loor G, Koch CG, Sabik JF 3rd, Li L, Blackstone EH. Implications and management of anemia in cardiac surgery: current state of knowledge. J Thorac Cardiovasc Surg 2012; 144: 538-46.
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: 2213-20.
Lannan KL, Sahler J, Spinelli SL, Phipps RP, Blumberg N. Transfusion immunomodulation—the case for leukoreduced and (perhaps) washed transfusions. Blood Cells Mol Dis 2013; 50: 61-8.
Baek JH, D’Agnillo F, Vallelian F, et al. Hemoglobin-driven pathophysiology is an in vivo consequence of the red blood cell storage lesion that can be attenuated in guinea pigs by haptoglobin therapy. J Clin Invest 2012; 122: 1444-58.
Karkouti K, Wijeysundera DN, Yau TM, et al. Advance targeted transfusion in anemic cardiac surgical patients for kidney protection: an unblinded randomized pilot clinical trial. Anesthesiology 2012; 116: 613-21.
Karkouti K, Wijeysundera DN, Yau TM, et al. In reply. Anesthesiology 2012; 117: 921-2.
Acknowledgement
The study was endorsed by the Canadian PACT (Perioperative Anesthesia Clinical Trials) group.
Funding sources
This study was funded in part by the Department of Anesthesia, University of Toronto. K Karkouti and CD Mazer are funded in part by a merit award from the Department of Anesthesia, University of Toronto. H Grocott received funding for his work on the project from the University of Manitoba Academic Oversight Committee.
Conflicts of interest
None declared.
Author information
Authors and Affiliations
Corresponding author
Additional information
Authorship contributions
All authors have made substantial contributions to the conception and design of the study and to the acquisition and interpretation of data. Keyvan Karkouti conducted the analysis and wrote the first draft of the manuscript. All authors took part in manuscript revision.
Rights and permissions
About this article
Cite this article
Karkouti, K., Grocott, H.P., Hall, R. et al. Interrelationship of preoperative anemia, intraoperative anemia, and red blood cell transfusion as potentially modifiable risk factors for acute kidney injury in cardiac surgery: a historical multicentre cohort study. Can J Anesth/J Can Anesth 62, 377–384 (2015). https://doi.org/10.1007/s12630-014-0302-y
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12630-014-0302-y