Anesthetics influence the incidence of acute kidney injury following valvular heart surgery
Authors: Young-Chul Yoo, Jae-Kwang Shim, Young Song, So-Young Yang, Young-Lan Kwak
Journal: Kidney International (2014)

Propofol has been shown to provide protection against renal ischemia/reperfusion injury experimentally, but clinical evidence is lacking. Here we studied the effect of propofol anesthesia on the occurrence of acute kidney injury following heart surgery with cardiopulmonary bypass. One hundred and twelve patients who underwent valvular heart surgery were randomized to receive either propofol or sevoflurane anesthesia, both with sufentanil. Using Acute Kidney Injury Network criteria, significantly fewer patients developed acute kidney injury postoperatively in the propofol group compared with the sevoflurane group (6 compared with 21 patients). The incidence of severe renal dysfunction was significantly higher in the sevoflurane group compared with the propofol group (5 compared with none). The postoperative cystatin C was significantly lower in the propofol group at 24 and 48h. Serum interleukin-6 at 6h after aorta cross-clamp removal, C-reactive protein at postoperative day 1, and segmented neutrophil counts at postoperative day 3 were also significantly lower in the propofol group. Thus, propofol anesthesia significantly reduced the incidence and severity of acute kidney injury in patients undergoing valvular heart surgery with cardiopulmonary bypass compared with sevoflurane. This beneficial effect of propofol may be related to its ability to attenuate the perioperative increase in proinflammatory mediators. Propofol has been shown to provide protection against renal ischemia/reperfusion injury experimentally, but clinical evidence is lacking. Here we studied the effect of propofol anesthesia on the occurrence of acute kidney injury following heart surgery with cardiopulmonary bypass. One hundred and twelve patients who underwent valvular heart surgery were randomized to receive either propofol or sevoflurane anesthesia, both with sufentanil. Using Acute Kidney Injury Network criteria, significantly fewer patients developed acute kidney injury postoperatively in the propofol group compared with the sevoflurane group (6 compared with 21 patients). The incidence of severe renal dysfunction was significantly higher in the sevoflurane group compared with the propofol group (5 compared with none). The postoperative cystatin C was significantly lower in the propofol group at 24 and 48h. Serum interleukin-6 at 6h after aorta cross-clamp removal, C-reactive protein at postoperative day 1, and segmented neutrophil counts at postoperative day 3 were also significantly lower in the propofol group. Thus, propofol anesthesia significantly reduced the incidence and severity of acute kidney injury in patients undergoing valvular heart surgery with cardiopulmonary bypass compared with sevoflurane. This beneficial effect of propofol may be related to its ability to attenuate the perioperative increase in proinflammatory mediators. Acute kidney injury (AKI) following cardiac surgery, even when mild and transient, undoubtedly poses the patients to increased risk of prolonged intensive care unit (ICU) stay, morbidity, and mortality.1.Lassnigg A. Schmidlin D. Mouhieddine M. et al.Minimal changes of serum creatinine predict prognosis in patients after cardiothoracic surgery: a prospective cohort study.J Am Soc Nephrol. 2004; 15: 1597-1605Crossref PubMed Scopus (1090) Google Scholar,2.Ryckwaert F. Boccara G. Frappier J.M. et al.Incidence, risk factors, and prognosis of a moderate increase in plasma creatinine early after cardiac surgery.Crit Care Med. 2002; 30: 1495-1498Crossref PubMed Scopus (133) Google Scholar Yet, its prevention proves to be difficult as the reported incidence of AKI reaches up to 40% depending on the type of surgery and the adopted definition of it.1.Lassnigg A. Schmidlin D. Mouhieddine M. et al.Minimal changes of serum creatinine predict prognosis in patients after cardiothoracic surgery: a prospective cohort study.J Am Soc Nephrol. 2004; 15: 1597-1605Crossref PubMed Scopus (1090) Google Scholar, 2.Ryckwaert F. Boccara G. Frappier J.M. et al.Incidence, risk factors, and prognosis of a moderate increase in plasma creatinine early after cardiac surgery.Crit Care Med. 2002; 30: 1495-1498Crossref PubMed Scopus (133) Google Scholar, 3.Choi Y.S. Shim J.K. Kim J.C. et al.Effect of remote ischemic preconditioning on renal dysfunction after complex valvular heart surgery: a randomized controlled trial.J Thorac Cardiovasc Surg. 2011; 142: 148-154Abstract Full Text Full Text PDF PubMed Scopus (119) Google Scholar The underlying mechanisms involved in the pathogenesis of AKI after cardiac surgery are multifactorial and are not completely understood, currently. Still, apart from the patient-related factors, cardiopulmonary bypass (CPB), which inevitably causes oxidative stress, ischemia–reperfusion (I/R) injury, and systemic inflammatory response, has been constantly incriminated as a major factor in causing AKI.4.Rosner M.H. Okusa M.D. Acute kidney injury associated with cardiac surgery.Clin J Am Soc Nephrol. 2006; 1: 19-32Crossref PubMed Scopus (823) Google Scholar,5.Massoudy P. Wagner S. Thielmann M. et al.Coronary artery bypass surgery and acute kidney injury—impact of the off-pump technique.Nephrol Dial Transplant. 2008; 23: 2853-2860Crossref PubMed Scopus (64) Google Scholar Even in the absence of a surgery-related overt ischemic insult by vascular clamps, CPB invariably causes injury to the renal medulla as it is prone to ischemic damage for having a unique blood supply with a limited oxygen reserve.4.Rosner M.H. Okusa M.D. Acute kidney injury associated with cardiac surgery.Clin J Am Soc Nephrol. 2006; 1: 19-32Crossref PubMed Scopus (823) Google Scholar Propofol is a widely used intravenous anesthetic agent, which bears structural similarity with the endogenous antioxidant α-tocoferol.6.Murphy P.G. Myers D.S. Davies M.J. et al.The antioxidant potential of propofol (2,6-diisopropylphenol).Br J Anaesth. 1992; 68: 613-618Crossref PubMed Scopus (330) Google Scholar Propofol also has been shown to possess anti-inflammatory and immune-modulatory properties.7.Rodriguez-Lopez J.M. Sanchez-Conde P. Lozano F.S. Laboratory investigation: effects of propofol on the systemic inflammatory response during aortic surgery.Can J Anaesth. 2006; 53: 701-710Crossref PubMed Scopus (46) Google Scholar,8.Sanchez-Conde P. Rodriguez-Lopez J.M. Nicolas J.L. et al.The comparative abilities of propofol and sevoflurane to modulate inflammation and oxidative stress in the kidney after aortic cross-clamping.Anesth Analg. 2008; 106: 371-378Crossref PubMed Scopus (66) Google Scholar While volatile anesthetics have been well known to exert organ-protective effect against I/R injury experimentally, several animal studies suggested that propofol was more effective in attenuating the development of AKI after exposure to anoxic circumstances when compared with the volatile anesthetic agents.7.Rodriguez-Lopez J.M. Sanchez-Conde P. Lozano F.S. Laboratory investigation: effects of propofol on the systemic inflammatory response during aortic surgery.Can J Anaesth. 2006; 53: 701-710Crossref PubMed Scopus (46) Google Scholar,8.Sanchez-Conde P. Rodriguez-Lopez J.M. Nicolas J.L. et al.The comparative abilities of propofol and sevoflurane to modulate inflammation and oxidative stress in the kidney after aortic cross-clamping.Anesth Analg. 2008; 106: 371-378Crossref PubMed Scopus (66) Google Scholar Considering the putative mechanisms leading to AKI, the antioxidant and anti-inflammatory properties of propofol may theoretically be able to attenuate renal injury in patients undergoing cardiac surgery with CPB. Although cumulative evidence suggests the lack of renoprotective effect by volatile anesthetics in cardiac surgical patients despite their solid experimental background,9.Lee H.T. Ota-Setlik A. Fu Y. et al.Differential protective effects of volatile anesthetics against renal ischemia–reperfusion injury in vivo.Anesthesiology. 2004; 101: 1313-1324Crossref PubMed Scopus (192) Google Scholar,10.Sindhvananda W. Phisaiphun K. Prapongsena P. No renal protection from volatile-anesthetic preconditioning in open heart surgery.J Anesth. 2013; 27: 48-55Crossref PubMed Scopus (13) Google Scholar a trial validating the efficacy of propofol as an anesthetic agent on preventing AKI after cardiac surgery would be worth noting. The aim of this prospective, randomized, and controlled trial was to investigate the effect of propofol anesthesia on renal protection in patients undergoing CPB for valvular heart surgery, which comprises a high risk for AKI. Valvular heart surgery was performed as planned in all patients, and complete follow-up data until discharge from the 112 patients were analyzed without any missing data. No relevant clinical problem occurred with either of the two anesthetic methods. Patients’ demographics, preoperative characteristics including Cleveland Clinic score and EuroSCORE, and surgeries performed were similar between two groups (Table 1).Table 1Patient demographics and preoperative clinical dataVariablesSevoflurane (n=56)Propofol (n=56)Age (years)58.8±12.358.1±12.2Female gender32 (57.1)29 (51.8)Body mass index (kg/m2)23.3±3.324.1±3.7Operation Aortic valve replacement18 (32.1)18 (32.1) Mitral valve replacement only28 (50)24 (42.9) Mitral valve replacement with TAP6 (10.7)6 (10.7) Double valve replacement2 (3.6)5 (8.9) Bental1 (1.8)2 (3.6) Redo1 (1.8)1 (1.8)Diabetes mellitus7 (12.5)9 (16.1)Hypertension16 (28.6)18 (32.1)Cerebrovascular accidents7 (12.7)4 (7.1)Congestive heart failure5 (8.9)4 (7.1)Chronic obstructive pulmonary disease2 (3.6)1 (1.8)NYHA classification I24 (42.9)27 (48.2) II28 (50)27 (48.2) III4 (7.1)2 (3.6)Preoperative ejection fraction63.1±10.165.2±11.3Medications β-Blockers20 (35.7)16 (28.6) Calcium channel blockers14 (25)11 (19.6) Renin–angiotensin system antagonist20 (35.7)21 (37.5) Diuretics36 (64.3)35 (62.5)EuroSCORE2.9±1.73.2±2.3Cleveland Clinic score1.8±0.81.9±0.7Abbreviations: NYHA, New York Heart Association; TAP, tricuspid annuloplasty.Values are mean±s.d. or number of patients (%). Open table in a new tab Abbreviations: NYHA, New York Heart Association; TAP, tricuspid annuloplasty. Values are mean±s.d. or number of patients (%). Operative data including durations of anesthesia, aortic cross-clamp (ACC) and CPB, fluid balance including the amounts of ultrafiltration, and packed erythrocyte transfusion requirement were similar between the two groups. The amount of norepinephrine required during the operation was significantly greater in the sevoflurane group (Table 2). In the propofol group, the infusion rates of propofol were 106±36 and 125±38μg/kg/min during CPB and the entire operation period, respectively. Intraoperative hemodynamic variables including cardiac index were comparable between the groups (Table 3).Table 2Intraoperative parametersVariablesSevoflurane (n=56)Propofol (n=56)P-valueAnesthesia time (min)187±49188±460.978Aortic cross-clamp time (min)70±2468±240.583Cardiopulmonary bypass time (min)96±3194±290.598Amount of ultrafiltration (ml)816±513861±6380.630Fluid balance Crystalloid (ml)1345±458.71269.8±454.90.850 Colloid (ml)439.2±223438.9±157.20.995 Urine output (ml)1145±446.51005.9±368.70.075Transfusion Amount of cell saver (ml)567±189558±2270.818 Amount of erythrocyte (unit)0.4±0.70.3±0.50.500 Patients transfused with erythrocyte18 (32.1)17 (30.4)0.838Vasopressors needs Mean norepinephrine dose during cardiopulmonary bypass (μg/kg/min)0.04±0.020.03±0.030.110 Mean norepinephrine dose during operation (μg/kg/min)0.05±0.030.03±0.030.004 Patients needed vasopressin45 (80.4)37 (67.1)0.088 Vasopressin dose during CPB (unit)1.41±1.440.96±1.350.105 Vasopressin dose during operation (unit)2.18±2.351.41±20.061Abbreviations: Amount of erythrocyte, number of units of erythrocyte transfused for the entire study group divided by the total number of subjects in that study group; CPB, cardiopulmonary bypass.Values are mean±s.d. or number of patients (%). Open table in a new tab Table 3Intraoperative hemodynamic changeVariablesSevoflurane (n=56)Propofol (n=56)Estimate (95% CI)P-valueHeart rate (b.p.m.)0.772aP Group × Time, P-value of the group and time interaction obtained by the linear mixed model. Before induction75.5±16.776.3±12.9–0.804 (–6.344 to 4.736)>0.999 After induction64.3±11.765.1±10.5–0.875 (–4.992 to 3.242)>0.999 Pericardium open68.2±12.467.8±10.80.46 (–3.865 to 4.758)>0.999 Postcardiopulmonary bypass81±1380.7±11.30.321 (–4.192 to 4.834)>0.999 Sternum closure89.9±14.787.2±14.22.804 (–2.560 to 8.167)>0.999Mean arterial pressure (mmHg)0.505aP Group × Time, P-value of the group and time interaction obtained by the linear mixed model. Before induction91.6±12.293.6±13.6–2.036 (–6.821 to 2.750)>0.999 After induction78.5±9.478.1±11.10.357 (–3.459 to 4.173)>0.999 Pericardium open72±9.675.2±11.6–3.321 (–7.273 to 0.631)>0.999 Postcardiopulmonary bypass69.8±10.773.2±12–3.393 (–7.607 to 0.821)>0.999 Sternum closure69.5±8.171.3±9.1–1.821 (–5.034 to 1.391)>0.999Pulmonary capillary wedge pressure (mmHg)0.733aP Group × Time, P-value of the group and time interaction obtained by the linear mixed model. Before induction17.7±617.1±60.768 (–1.416 to 2.951)>0.999 After induction16.1±4.914.7±4.81.482 (–0.306 to 3.270)>0.999 Pericardium open16.1±5.315.2±4.70.964 (–0.899 to 2.828)>0.999 Postcardiopulmonary bypass15.3±3.814.8±3.60.446 (–0.919 to 1.812)>0.999 Sternum closure16.3±3.915.6±3.50.679 (–0.683 to 2.040)>0.999Central venous pressure (mmHg))0.366aP Group × Time, P-value of the group and time interaction obtained by the linear mixed model. Before induction8.9±2.68.9±3.10.000 (–1.072 to 1.072)>0.999 After induction8.9±2.48.8±2.80.125 (–0.859 to 1.109)>0.999 Pericardium open8.6±2.28.6±2.6–0.018 (–0.902 to 0.867)>0.999 Postcardiopulmonary bypass10.3±2.89.4±2.60.946 (–0.055 to 1.948)>0.999 Sternum closure11.1±2.210.3±2.50.821 (–0.045 to 1.688)>0.999Cardiac index (l/min/m2)0.725aP Group × Time, P-value of the group and time interaction obtained by the linear mixed model. Before induction2.5±0.62.6±0.6–0.045 (–0.275 to 0.185)>0.999 After induction2.4±0.72.5±0.7–0.129 (–0.387 to 0.129)>0.999 Pericardium open2.3±0.52.5±0.6–0.146 (–0.340 to 0.047)>0.999 Postcardiopulmonary bypass2.7±0.62.8±0.8–0.125 (–0.384 to 0.134)>0.999 Sternum closure2.8±0.62.9±0.7–0.141 (–0.378 to 0.095)>0.999Abbreviations: CI, confidence interval; CPB, cardiopulmonary bypass; pericardium open, 5min after pericardium opening; postcardiopulmonary bypass, 15min after weaning from CPB; after induction, 15min after anesthetic induction; before induction, before anesthetic induction.Values are mean±s.d.a P Group × Time, P-value of the group and time interaction obtained by the linear mixed model. Open table in a new tab Abbreviations: Amount of erythrocyte, number of units of erythrocyte transfused for the entire study group divided by the total number of subjects in that study group; CPB, cardiopulmonary bypass. Values are mean±s.d. or number of patients (%). Abbreviations: CI, confidence interval; CPB, cardiopulmonary bypass; pericardium open, 5min after pericardium opening; postcardiopulmonary bypass, 15min after weaning from CPB; after induction, 15min after anesthetic induction; before induction, before anesthetic induction. Values are mean±s.d. The total amount of infused fluid, blood loss, and urine output until 72h after the operation was comparable between the groups. However, furosemide requirements during the first 24h (P=0.035) and 48–72h (P=0.029) after the operation were significantly higher in the sevoflurane group compared with the propofol group (Table 4).Table 4Postoperative fluid balanceVariablesSevoflurane (n=56)Propofol (n=56)P-valueCrystalloid (ml) ICU arrival ~24h3555±7743313±9710.148 24–48h2054±7932168±8600.466 48–72h1287±10801128±7670.401Colloid (ml) ICU arrival ~24h301±270334±2740.533 24–48h35±12240±960.804 48–72h2±136±270.271Blood loss (ml) ICU arrival ~24h382±338394±3840.856 24–48h230±169218±1720.712 48–72h95±9298±1080.884Urine output (ml) ICU arrival ~24h2802±7952862±7760.689 24–48h2543±7862716±8970.279 48–72h2082±11052341±10490.206Diuretics usage (mg) 0–24h13.1±13.98.6±7.80.035 24–48h29.7±49.724.2±31.90.485 48–72h11.3±23.93.9±7.40.029Abbreviations: Diuretics usage, daily accumulated dose of furosemide; ICU, intensive care unit.Between-group comparisons of the variables during corresponding periods were performed by the independent Student’s t-test.Values are mean±s.d. Open table in a new tab Abbreviations: Diuretics usage, daily accumulated dose of furosemide; ICU, intensive care unit. Between-group comparisons of the variables during corresponding periods were performed by the independent Student’s t-test. Values are mean±s.d. Postoperatively, AKI occurred in 21 patients (37.5%) of the sevoflurane group compared with only 6 patients (10.7%) of the propofol group (P=0.001). The number of patients with urine output of <0.5ml/kg per hour continuously over 6h but within 48h after the operation was 9 (16.1%) in the sevoflurane group and 2 (3.6%) in the propofol group, respectively (P=0.026). Five (8.9%) patients were diagnosed with AKI classified as Acute Kidney Injury Network stage 2 or 3 and two of these patients received dialysis in the sevoflurane group, while none in the propofol group (P=0.022). The interaction of group and time in the creatinine, cystatin C, and creatine kinase-MB (CK-MB) levels (P=0.027, 0.009, and 0.031, respectively) were significant between the groups in the linear mixed-model analysis. Post hoc analysis with Bonferonni correction revealed that cystatin C levels at 24 and 48h postoperatively and creatine kinase-MB (CK-MB) levels at 48h postoperatively were significantly lower in the propofol group compared with the sevoflurane group. The number of patients in whom estimated glomerular filtration rate (eGFR) declined >30% from the baseline value was significantly greater in the sevoflurane group compared with the propofol group (18 (32.1%) vs. 5 (8.9%), P=0.002). The number of patients showing an increase in cystatin C levels >25% from the baseline value was greater in the sevoflurane group than in the propofol group (22 (39.3%) vs. 11 (19.6%), P=0.023) (Table 5).Table 5Variables associated with renal and cardiac outcomesVariablesSevoflurane (n=56)Propofol (n=56)Estimate (95% CI)P-valuePostoperative AKIaAnalyzed with highest creatinine value during postoperative 48h.0.007 No AKI35 (62.5)50 (89.3) Stage 116 (28.6)6 (10.7) Stage 23 (5.4)0 (0) Stage 32 (3.6)0 (0)Oliguria within 48h9 (16.1)2 (3.6)0.026Postoperative dialysis2 (3.6)0 (0)0.154Creatinine increased 25% or moreaAnalyzed with highest creatinine value during postoperative 48h.28 (50)17 (30.4)0.034eGFR declined 30% or moreaAnalyzed with highest creatinine value during postoperative 48h.18 (32.1)5 (8.9)0.002Cystatin C increased 25% or more22 (39.3)11 (19.6)0.023Creatinine (mg/dl)0.027bPGroup × Time, P-value of the group and time interaction obtained by the linear mixed model. Baseline0.85±0.180.84±0.180.011 (-0.057 to 0.078)>0.999 ICU arrival0.78±0.180.76±0.160.020 (-0.042 to 0.083)>0.999 POD 1cAnalyzed with highest creatinine value during corresponding period.1.12±0.460.95±0.240.170 (0.033 to 0.306)0.084 POD 2cAnalyzed with highest creatinine value during corresponding period.1.02±0.400.88±0.280.139 (0.011 to 0.267)0.178 POD 3cAnalyzed with highest creatinine value during corresponding period.0.89±0.280.78±0.20.110 (0.018 to 0.201)0.102eGFR (ml/minper1.73m2)0.063bPGroup × Time, P-value of the group and time interaction obtained by the linear mixed model. Baseline85.6±1985.9±18-0.270 (-7.116 to 6.577)>0.999 ICU arrival91.6±18.992.8±17.1-1.185 (-7.871 to 5.501)>0.999 POD 1cAnalyzed with highest creatinine value during corresponding period.71.9±27.578.1±21.2-6.284 (-15.373 to 2.805)>0.999 POD 2cAnalyzed with highest creatinine value during corresponding period.76.8±26.884.1±25.7-7.336 (-17.059 to 2.388)>0.999 POD 3cAnalyzed with highest creatinine value during corresponding period.84.6±23.291.2±18.9-6.619 (-14.450 to 1.212)>0.999Cystatin C (mg/dl)0.009bPGroup × Time, P-value of the group and time interaction obtained by the linear mixed model. Baseline0.96±0.200.92±0.160.040 (-0.026 to 0.106)0.965 ICU arrival0.86±0.170.84±0.200.006 (-0.056 to 0.068)>0.999 24h1.11±0.410.92±0.240.167 (0.040 to 0.294)0.044 48h1.21±0.430.93±0.350.170 (0.045 to 0.295)0.035CK-MB (ng/ml)0.031bPGroup × Time, P-value of the group and time interaction obtained by the linear mixed model. Baseline2.3±1.22.3±0.70.194 (-0.407 to 0.796)>0.999 24h43.4±47.328.2±20.414.729 (1.151 to 28.306)0.108 48h26.2±17.919±87.376 (2.173 to 12.579)0.019Abbreviations: AKI, acute kidney injury; CI, confidence interval; CK-MB, creatine kinase-MB; eGFR, estimated glomerular filtration rate; ICU, intensive care unit; oliguria within 48h, the patients with urine output of <0.5ml/kg/h for >6h continuously within 48h after the operation; POD, postoperative days.Values are number of patients (%) or mean±s.d.a Analyzed with highest creatinine value during postoperative 48h.b PGroup × Time, P-value of the group and time interaction obtained by the linear mixed model.c Analyzed with highest creatinine value during corresponding period. Open table in a new tab Abbreviations: AKI, acute kidney injury; CI, confidence interval; CK-MB, creatine kinase-MB; eGFR, estimated glomerular filtration rate; ICU, intensive care unit; oliguria within 48h, the patients with urine output of <0.5ml/kg/h for >6h continuously within 48h after the operation; POD, postoperative days. Values are number of patients (%) or mean±s.d. The interaction of group and time in serum interleukin (IL)-6, C-reactive protein (CRP) levels, and segmented neutrophil counts (P=0.019, 0.027, and 0.007, respectively) were significant between the groups in the linear mixed-model analysis. After post hoc analysis with Bonferonni correction, serum levels of IL-6 were significantly lower in the propofol group at 6h after declamping of ACC, and serum concentration of CRP at postoperative day (POD) 1 and segmented neutrophil counts at POD 3 were significantly lower in the propofol group compared with the sevoflurane group (Figure 1). The length of hospital stay was significantly shorter in the propofol group compared with the sevoflurane group, whereas other postoperative outcomes including duration of ventilator care, ICU stay, and in-hospital mortality were similar between the groups (Table 6).Table 6Postoperative outcomeVariableSevoflurane (n=56)Propofol (n=56)P-valueReoperation for bleeding1 (1.8)0 (0)0.315Reintubation0 (0)0 (0)0.999Duration of ventilator care (h)18.6±9.516.8±8.40.286Duration of ICU stay (days)3.1±1.72.6±0.60.051Duration of hospital stay (days)15.6±7.512.3±3.90.005In-hospital mortality0 (0)0 (0)0.999Abbreviations: ICU, intensive care unit.Values are mean±s.d. or number of patients (%). Open table in a new tab Abbreviations: ICU, intensive care unit. Values are mean±s.d. or number of patients (%). None of the patients developed unexplained lactic acidosis, rhabdomyolysis, or dyslipidemia, indicating propofol infusion syndrome. In spite of advances in CPB technology, the incidence of AKI after cardiac surgery has increased during the past decade.11.Thakar C.V. Worley S. Arrigain S. et al.Improved survival in acute kidney injury after cardiac surgery.Am J Kidney Dis. 2007; 50: 703-711Abstract Full Text Full Text PDF PubMed Scopus (82) Google Scholar The pathogenesis of AKI after cardiac surgery encompasses complex interplays among multiple factors, CPB-related I/R injury, oxidative stress, and activation of systemic inflammatory reaction have been regarded as major determinants.4.Rosner M.H. Okusa M.D. Acute kidney injury associated with cardiac surgery.Clin J Am Soc Nephrol. 2006; 1: 19-32Crossref PubMed Scopus (823) Google Scholar,5.Massoudy P. Wagner S. Thielmann M. et al.Coronary artery bypass surgery and acute kidney injury—impact of the off-pump technique.Nephrol Dial Transplant. 2008; 23: 2853-2860Crossref PubMed Scopus (64) Google Scholar Numerous strategies including pharmacologic and non-pharmacologic interventions have been attempted to prevent AKI associated with cardiac surgery without noticeable efficacy.12.Gude D. Jha R. Acute kidney injury following cardiac surgery.Ann Card Anaesth. 2012; 15: 279-286Crossref PubMed Scopus (15) Google Scholar,13.Schetz M. Bove T. Morelli A. et al.Prevention of cardiac surgery-associated acute kidney injury.Int J Artif Organs. 2008; 31: 179-189PubMed Google Scholar Propofol is a widely used intravenous anesthetic agent with a proven antioxidant activity similar to α-tocoferol.6.Murphy P.G. Myers D.S. Davies M.J. et al.The antioxidant potential of propofol (2,6-diisopropylphenol).Br J Anaesth. 1992; 68: 613-618Crossref PubMed Scopus (330) Google Scholar Propofol was also reported to modulate inflammatory reactions and oxidative stress in cardiac surgical patients.7.Rodriguez-Lopez J.M. Sanchez-Conde P. Lozano F.S. Laboratory investigation: effects of propofol on the systemic inflammatory response during aortic surgery.Can J Anaesth. 2006; 53: 701-710Crossref PubMed Scopus (46) Google Scholar,8.Sanchez-Conde P. Rodriguez-Lopez J.M. Nicolas J.L. et al.The comparative abilities of propofol and sevoflurane to modulate inflammation and oxidative stress in the kidney after aortic cross-clamping.Anesth Analg. 2008; 106: 371-378Crossref PubMed Scopus (66) Google Scholar The renoprotective effects of propofol against I/R injury has been demonstrated in animal experiments using renal artery or abdominal aorta clamping model,14.Yuzbasioglu M.F. Aykas A. Kurutas E.B. et al.Protective effects of propofol against ischemia/reperfusion injury in rat kidneys.Ren Fail. 2010; 32: 578-583Crossref PubMed Scopus (33) Google Scholar,15.Yuzer H. Yuzbasioglu M.F. Ciralik H. et al.Effects of intravenous anesthetics on renal ischemia/reperfusion injury.Ren Fail. 2009; 31: 290-296Crossref PubMed Scopus (37) Google Scholar and has also been reported to be superior to that of volatile anesthetics.8.Sanchez-Conde P. Rodriguez-Lopez J.M. Nicolas J.L. et al.The comparative abilities of propofol and sevoflurane to modulate inflammation and oxidative stress in the kidney after aortic cross-clamping.Anesth Analg. 2008; 106: 371-378Crossref PubMed Scopus (66) Google Scholar However, the renoprotective effect of propofol in cardiac surgical patients remains elusive and no comprehensive data exist in that regard. In the current study, the incidence of AKI in the propofol group was 10.5% according to the Acute Kidney Injury Network criteria.16.Englberger L. Suri R.M. Li Z. et al.Clinical accuracy of RIFLE and Acute Kidney Injury Network (AKIN) criteria for acute kidney injury in patients undergoing cardiac surgery.Crit Care. 2011; 15: R16Crossref PubMed Scopus (221) Google Scholar On the contrary, the incidence of AKI in the sevoflurane group was 37.5%, which was comparable to that of previous studies.1.Lassnigg A. Schmidlin D. Mouhieddine M. et al.Minimal changes of serum creatinine predict prognosis in patients after cardiothoracic surgery: a prospective cohort study.J Am Soc Nephrol. 2004; 15: 1597-1605Crossref PubMed Scopus (1090) Google Scholar,2.Ryckwaert F. Boccara G. Frappier J.M. et al.Incidence, risk factors, and prognosis of a moderate increase in plasma creatinine early after cardiac surgery.Crit Care Med. 2002; 30: 1495-1498Crossref PubMed Scopus (133) Google Scholar Moreover, AKI in the propofol group was confined to stage 1 of the Acute Kidney Injury Network criteria, whereas AKI in the sevoflurane group demonstrated various disease spectrum including dialysis requirement with significantly more number of patients having severe renal dysfunction. Also, significantly less patients in the propofol group developed eGFR decline of >30% and increase in serum creatinine level of >25% from baseline than in the sevoflurane group. Patients who developed a postoperative reduction in eGFR of >30% from baseline had a remarkably higher mortality,17.Thakar C.V. Worley S. Arrigain S. et al.Influence of renal dysfunction on mortality after cardiac surgery: modifying effect of preoperative renal function.Kidney Int. 2005; 67: 1112-1119Abstract Full Text Full Text PDF PubMed Scopus (247) Google Scholar and increase in serum creatinine level of >25% from baseline was associated with a hazard ratio of 1.63 for long-term mortality at 100 months after hospital discharge.18.Loef B.G. Epema A.H. Smilde T.B. et al.Immediate postoperative renal function deterioration in cardiac surgical patients predicts in-hospital mortality and long-term survival.J Am Soc Nephrol. 2005; 16: 195-200Crossref PubMed Scopus (388) Google Scholar In contrast to our results, one previous study comparing sevoflurane and propofol anesthesia reported no significant difference in the incidence of AKI.19.Story D.A. Poustie S. Liu G. et al.Changes in plasma creatinine concentration after cardiac anesthesia with isoflurane, propofol, or sevoflurane: a randomized clinical trial.Anesthesiology. 2001; 95: 842-848Crossref PubMed Scopus (50) Google Scholar The observed discrepancy may be explained by an inadequate target concentration of propofol. Although propofol concentrations producing renoprotection are unknown, that for cardioprotection has been reported to between 25 and 50mmol/l (4.5–8.9μg/ml) and the predicted infusion rate to achieve a mean plasma concentration of 5μg/ml was 113μg/kg per min during CPB.20.Raedschelders K. Hui Y. Laferlita B. et al.Target-achieved propofol concentration during on-pump cardiac surgery: a pilot dose-finding study.Can J Anaesth. 2009; 56: 658-666Crossref Pu