Background: Acute kidney injury (AKI) is common in patients undergoing cardiac surgery and is associated with a high rate of death, long-term sequelae and healthcare costs. We conducted a systematic review of randomized controlled trials for strategies to prevent or treat AKI in cardiac surgery. Methods: We screened Medline, Scopus, Cochrane Renal Library, and Google Scholar for randomized controlled trails in cardiac surgery for prevention or treatment of AKI in adults. Results: We identified 70 studies that contained a total of 5,554 participants published until November 2008. Most studies were small in sample size, were single-center, focused on preventive strategies, and displayed wide variation in AKI definitions. Only 26% were assessed to be of high quality according to the Jadad criteria. The types of strategies with possible protective efficacy were dopaminergic agents, vasodilators, anti-inflammatory agents, and pump/perfusion strategies. When analyzed separately, dopamine and N-acetylcysteine did not reduce the risk for AKI. Conclusions: This summary of all the literature on prevention and treatment strategies for AKI in cardiac surgery highlights the need for better information. The results advocate large, good-quality, multicenter studies to determine whether promising interventions reliably reduce rates of acute renal replacement therapy and mortality in the cardiac surgery setting.

Keywords:
Acute kidney injury, prevention, Cardiac surgery, Healthcare costs
1.
Chertow GM, Levy EM, Hammermeister KE, Grover F, Daley J: Independent association between acute renal failure and mortality following cardiac surgery. Am J Med 1998;104:343–348.
2.
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.
3.
Chertow GM, Christiansen CL, Cleary PD, Munro C, Lazarus JM: Prognostic stratification in critically ill patients with acute renal failure requiring dialysis. Arch Intern Med 1995;155:1505–1511.
4.
Zanardo G, Michielon P, Paccagnella A, et al: Acute renal failure in the patient undergoing cardiac operation. Prevalence, mortality rate, and main risk factors. J Thorac Cardiovasc Surg 1994;107:1489–1495.
5.
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;15:1597–1605.
6.
Nalysnyk L, Fahrbach K, Reynolds MW, Zhao SZ, Ross S: Adverse events in coronary artery bypass graft (CABG) trials: a systematic review and analysis. Heart 2003;89:767–772.
7.
Abu-Omar Y, Ratnatunga C: Cardiopulmonary bypass and renal injury. Perfusion 2006;21:209–213.
8.
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.
9.
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.
10.
Zacharias M, Conlon NP, Herbison GP, Sivalingam P, Walker RJ, Hovhannisyan K: Interventions for protecting renal function in the perioperative period. [update of Cochrane Database Syst Rev 2005;3:CD003590.]
11.
Moher D, Cook DJ, Eastwood S, Olkin I, Rennie D, Stroup DF: Improving the quality of reports of meta-analyses of randomised controlled trials: the QUOROM statement. Quality of Reporting of Meta-analyses. Lancet 1999;354:1896–1900.
12.
Jadad AR, Moore RA, Carroll D, et al: Assessing the quality of reports of randomized clinical trials: is blinding necessary? Control Clin Trials 1996;17:1–12.
13.
DerSimonian R, Laird N: Meta-analysis in clinical trials. Control Clin Trials 1986;7:177–188.
14.
Higgins JP, Thompson SG, Deeks JJ, Altman DG: Measuring inconsistency in meta-analyses. BMJ 2003;327:557–560.
15.
Terrin N, Schmid CH, Lau J, Olkin I: Adjusting for publication bias in the presence of heterogeneity. Stat Med 2003;22:2113–2126.
16.
Lau J, Ioannidis JP, Terrin N, Schmid CH, Olkin I: The case of the misleading funnel plot. BMJ 2006;333:597–600.
17.
Abe K, Fujino Y, Sakakibara T: The effect of prostaglandin E1 during cardiopulmonary bypass on renal function after cardiac surgery. Eur J Clin Pharmacol 1993;45:217–220.
18.
Adabag AS, Ishani A, Koneswaran S, et al: Utility of N-acetylcysteine to prevent acute kidney injury after cardiac surgery: a randomized controlled trial. Am Heart J 2008;155:1143–1149.
19.
Amano J, Suzuki A, Sunamori M: Salutary effect of reduced glutathione on renal function in coronary artery bypass operation. J Am Coll Surg 1994;179:714–720.
20.
Amano J, Suzuki A, Sunamori M, Tofukuji M: Effect of calcium antagonist diltiazem on renal function in open heart surgery. Chest 1995;107:1260–1265.
21.
Ascione R, Lloyd CT, Underwood MJ, Gomes WJ, Angelini GD: On-pump versus off-pump coronary revascularization: evaluation of renal function. Ann Thorac Surg 1999;68:493–498.
22.
Barr LF, Kolodner K: N-acetylcysteine and fenoldopam protect the renal function of patients with chronic renal insufficiency undergoing cardiac surgery. Crit Care Med 2008;36:1427–1435.
23.
Berendes E, Mollhoff T, Van Aken H, et al: Effects of dopexamine on creatinine clearance, systemic inflammation, and splanchnic oxygenation in patients undergoing coronary artery bypass grafting. Anesth Analg 1997;84:950–957.
24.
Bergman AS, Odar-Cederlof I, Westman L, Bjellerup P, Hoglund P, Ohqvist G: Diltiazem infusion for renal protection in cardiac surgical patients with preexisting renal dysfunction. J Cardiothorac Vasc Anesth 2002;16:294–299.
25.
Bolcal C, Akay HT, Bingol H, et al: Leukodepletion improves renal function in patients with renal dysfunction undergoing on-pump coronary bypass surgery: a prospective randomized study. Thorac Cardiovasc Surg 2007;55:89–93.
26.
Boldt J, Brosch C, Rohm K, Lehmann A, Mengistu A, Suttner S: Is albumin administration in hypoalbuminemic elderly cardiac surgery patients of benefit with regard to inflammation, endothelial activation, and long-term kidney function? Anesth Analg 2008;107:1496–1503.
27.
Bove T, Landoni G, Calabro MG, et al: Renoprotective action of fenoldopam in high-risk patients undergoing cardiac surgery: a prospective, double-blind, randomized clinical trial. Circulation 2005;111:3230–3235.
28.
Burns KE, Chu MW, Novick RJ, et al: Perioperative N-acetylcysteine to prevent renal dysfunction in high-risk patients undergoing CABG surgery: a randomized controlled trial. JAMA 2005;294:342–350.
29.
Caimmi PP, Pagani L, Micalizzi E, et al: Fenoldopam for renal protection in patients undergoing cardiopulmonary bypass. J Cardiothorac Vasc Anesth 2003;17:491–494.
30.
Carcoana OV, Mathew JP, Davis E, et al: Mannitol and dopamine in patients undergoing cardiopulmonary bypass: a randomized clinical trial. Anesth Analg 2003;97:1222–1229.
31.
Carrier M, Perrault LP, Jeanmart H, Martineau R, Cartier R, Page P: Randomized trial comparing off-pump to on-pump coronary artery bypass grafting in high-risk patients. Heart Surg Forum 2003;6:E89–E92.
32.
Celik JB, Gormus N, Topal A, Okesli S, Solak H: Effect of off-pump and on-pump coronary artery bypass grafting on renal function. Ren Fail 2005;27:183–188.
33.
Chen HH, Sundt TM, Cook DJ, Heublein DM, Burnett JC Jr: Low dose nesiritide and the preservation of renal function in patients with renal dysfunction undergoing cardiopulmonary-bypass surgery: a double-blind placebo-controlled pilot study. Circulation 2007;116:134–138.
34.
Cogliati AA, Vellutini R, Nardini A, et al: Fenoldopam infusion for renal protection in high-risk cardiac surgery patients: a randomized clinical study. J Cardiothorac Vasc Anesth 2007;21:847–850.
35.
Colson P, Ribstein J, Mimran A, Grolleau D, Chaptal PA, Roquefeuil B: Effect of angiotensin converting enzyme inhibition on blood pressure and renal function during open heart surgery. Anesthesiology 1990;72:23–27.
36.
Costa P, Ottino GM, Matani A, et al: Low-dose dopamine during cardiopulmonary bypass in patients with renal dysfunction. J Cardiothorac Anesth 1990;4:469–473.
37.
Dehne MG, Klein TF, Muhling J, Sablotzki A, Osmer C, Hempelmann G: Impairment of renal function after cardiopulmonary bypass is not influenced by dopexamine. Ren Fail 2001;23:217–230.
38.
Demirkilic U, Kuralay E, Yenicesu M, et al: Timing of replacement therapy for acute renal failure after cardiac surgery. J Card Surg 2004;19:17–20.
39.
Dural O, Ozkara A, Celebioglu b, Kanbak M, Ciliv G, Aypar U: Comparative study of dopamine and mannitol effects on renal function during cardiopulmonary bypass by using N-acetyl-beta-D-glucosaminidase assay. Turk J Med Sci 2000;30:453–457.
40.
Durmaz I, Yagdi T, Calkavur T, et al: Prophylactic dialysis in patients with renal dysfunction undergoing on-pump coronary artery bypass surgery. Ann Thorac Surg 2003;75:859–864.
41.
Fischer UM, Weissenberger WK, Warters RD, Geissler HJ, Allen SJ, Mehlhorn U: Impact of cardiopulmonary bypass management on postcardiac surgery renal function. Perfusion 2002;17:401–406.
42.
Gandhi GY, Nuttall GA, Abel MD, et al: Intensive intraoperative insulin therapy versus conventional glucose management during cardiac surgery: a randomized trial. Ann Intern Med 2007;146:233–243.
43.
Gatot I, Abramov D, Tsodikov V, et al: Should we give prophylactic renal-dose dopamine after coronary artery bypass surgery? J Card Surg 2004;19:128–133.
44.
Gerrah R, Ehrlich S, Tshori S, Sahar G: Beneficial effect of aspirin on renal function in patients with renal insufficiency postcardiac surgery. J Cardiovasc Surg 2004;45:545–550.
45.
Haase M, Haase-Fielitz A, Bagshaw SM, et al: Phase II, randomized, controlled trial of high-dose N-acetylcysteine in high-risk cardiac surgery patients. Crit Care Med 2007;35:1324–1331.
46.
Halpenny M, Lakshmi S, O’Donnell A, O’Callaghan-Enright S, Shorten GD: Fenoldopam: renal and splanchnic effects in patients undergoing coronary artery bypass grafting. Anaesthesia 2001;56:953–960.
47.
Hayashida N, Chihara S, Kashikie H, et al: Effects of intraoperative administration of atrial natriuretic peptide. Ann Thorac Surg 2000;70:1319–1326.
48.
Kaya K, Oguz M, Akar AR, et al: The effect of sodium nitroprusside infusion on renal function during reperfusion period in patients undergoing coronary artery bypass grafting: a prospective randomized clinical trial. Eur J Cardiothorac Surg 2007;31:290–297.
49.
Kocakulak M, Askin G, Kucukaksu S, Tarcan O, Piskin E: Pulsatile flow improves renal function in high-risk cardiac operations. Blood Purif 2005;23:263–267.
50.
Kramer BK, Preuner J, Ebenburger A, et al: Lack of renoprotective effect of theophylline during aortocoronary bypass surgery. Nephrol Dial Transplant 2002;17:910–915.
51.
Kulka PJ, Tryba M, Zenz M: Preoperative alpha2-adrenergic receptor agonists prevent the deterioration of renal function after cardiac surgery: results of a randomized, controlled trial. Crit Care Med 1996;24:947–952.
52.
Lassnigg A, Donner E, Grubhofer G, Presterl E, Druml W, Hiesmayr M: Lack of renoprotective effects of dopamine and furosemide during cardiac surgery. J Am Soc Nephrol 2000;11:97–104.
53.
Lema G, Urzua J, Jalil R, et al: Renal protection in patients undergoing cardiopulmonary bypass with preoperative abnormal renal function. Anesth Analg 1998;86:3–8.
54.
Loef BG, Henning RH, Epema AH, et al: Effect of dexamethasone on perioperative renal function impairment during cardiac surgery with cardiopulmonary bypass. Br J Anaesth 2004;93:793–798.
55.
Mahesh B, Yim B, Robson D, Pillai R, Ratnatunga C, Pigott D: Does furosemide prevent renal dysfunction in high-risk cardiac surgical patients? Results of a double-blinded prospective randomised trial. Eur J Cardiothorac Surg 2008;33:370–376.
56.
Marathias KP, Vassili M, Robola A, et al: Preoperative intravenous hydration confers renoprotection in patients with chronic kidney disease undergoing cardiac surgery. Artif Organs 2006;30:615–621.
57.
Masoumi M, Saidi MR, Rostami F, Sepahi H, Roushani D: Off-pump coronary artery bypass grafting in left ventricular dysfunction. Asian Cardiovasc Thorac Ann 2008;16:16–20.
58.
McBride WT, Allen S, Gormley SM, et al: Methylprednisolone favourably alters plasma and urinary cytokine homeostasis and subclinical renal injury at cardiac surgery. Cytokine 2004;27:81–89.
59.
Mentzer RM Jr, Oz MC, Sladen RN, et al: Effects of perioperative nesiritide in patients with left ventricular dysfunction undergoing cardiac surgery: the NAPA Trial. J Am Coll Cardiol 2007;49:716–726.
60.
Meyer M, Wiebe K, Wahlers T, et al: Urodilatin (INN:ularitide) as a new drug for the therapy of acute renal failure following cardiac surgery. Clin Exp Pharmacol Physiol 1997;24:374–376.
61.
Monaco M, Di Tommaso L, Mottola M, Stassano P, Iannelli G: Clinical outcome for on-pump myocardial revascularization in patients with mild renal dysfunction. Thorac Cardiovasc Surg 2005;53:46–51.
62.
Morgera S, Woydt R, Kern H, et al: Low-dose prostacyclin preserves renal function in high-risk patients after coronary bypass surgery. Crit Care Med 2002;30:107–112.
63.
Myles PS, Buckland MR, Schenk NJ, et al: Effect of ‘renal-dose’ dopamine on renal function following cardiac surgery. Anaesth Intensive Care 1993;21:56–61.
64.
Nuutinen L, Hollmen A: The effect of prophylactic use of furosemide on renal function during open heart surgery. Ann Chir Gynaecol 1976;65:258–266.
65.
Onorati F, Presta P, Fuiano G, et al: A randomized trial of pulsatile perfusion using an intra-aortic balloon pump versus nonpulsatile perfusion on short-term changes in kidney function during cardiopulmonary bypass during myocardial reperfusion. Am J Kidney Dis 2007;50:229–238.
66.
Piper SN, Kumle B, Maleck WH, et al: Diltiazem may preserve renal tubular integrity after cardiac surgery. Can J Anaesth 2003;50:285–292.
67.
Ristikankare A, Kuitunen T, Kuitunen A, et al: Lack of renoprotective effect of i.v. N-acetylcysteine in patients with chronic renal failure undergoing cardiac surgery. Br J Anaesth 2006;97:611–616.
68.
Ryckwaert F, Colson P, Ribstein J, Boccara G, Guillon G: Haemodynamic and renal effects of intravenous enalaprilat during coronary artery bypass graft surgery in patients with ischaemic heart dysfunction. Br J Anaesth 2001;86:169–175.
69.
Sajja LR, Mannam G, Chakravarthi RM, et al: Coronary artery bypass grafting with or without cardiopulmonary bypass in patients with preoperative non-dialysis dependent renal insufficiency: a randomized study. J Thorac Cardiovasc Surg 2007;133:378–388.
70.
Sezai A, Shiono M, Orime Y, et al: Low-dose continuous infusion of human atrial natriuretic peptide during and after cardiac surgery. Ann Thorac Surg 2000;69:732–738.
71.
Sezai A, Hata M, Wakui S, et al: Efficacy of continuous low-dose hANP administration in patients undergoing emergent coronary artery bypass grafting for acute coronary syndrome. Circ J 2007;71:1401–1407.
72.
Sirivella S, Gielchinsky I, Parsonnet V: Mannitol, furosemide, and dopamine infusion in postoperative renal failure complicating cardiac surgery. Ann Thorac Surg 2000;69:501–506.
73.
Sisillo E, Ceriani R, Bortone F, et al: N-acetylcysteine for prevention of acute renal failure in patients with chronic renal insufficiency undergoing cardiac surgery: a prospective, randomized, clinical trial. Crit Care Med 2008;36:81–86.
74.
Smith MN, Best D, Sheppard SV, Smith DC: The effect of mannitol on renal function after cardiopulmonary bypass in patients with established renal dysfunction. Anaesthesia 2008;63:701–704.
75.
Straka Z, Widimsky P, Jirasek K, et al: Off-pump versus on-pump coronary surgery: final results from a prospective randomized study PRAGUE-4. Ann Thorac Surg 2004;77:789–793.
76.
Sumeray M, Robertson C, Lapsley M, Bomanji J, Norman AG, Woolfson RG: Low dose dopamine infusion reduces renal tubular injury following cardiopulmonary bypass surgery. J Nephrol 2001;14:397–402.
77.
Sward K, Valsson F, Odencrants P, Samuelsson O, Ricksten SE: Recombinant human atrial natriuretic peptide in ischemic acute renal failure: a randomized placebo-controlled trial. Crit Care Med 2004;32:1310–1315.
78.
Tang AT, Alexiou C, Hsu J, Sheppard SV, Haw MP, Ohri SK: Leukodepletion reduces renal injury in coronary revascularization: a prospective randomized study. Ann Thorac Surg 2002;74:372–377.
79.
Tang AT, Knott J, Nanson J, Hsu J, Haw MP, Ohri SK: A prospective randomized study to evaluate the renoprotective action of beating heart coronary surgery in low risk patients. Eur J Cardiothorac Surg 2002;22:118–123.
80.
Tang AT, El-Gamel A, Keevil B, Yonan N, Deiraniya AK: The effect of ‘renal-dose’ dopamine on renal tubular function following cardiac surgery: assessed by measuring retinol binding protein (RBP). Eur J Cardiothorac Surg 1999;15:717–721.
81.
Wijeysundera DN, Beattie WS, Rao V, Granton JT, Chan CT: N-acetylcysteine for preventing acute kidney injury in cardiac surgery patients with pre-existing moderate renal insufficiency. Can J Anaesth 2007;54:872–881.
82.
Witczak BJ, Hartmann A, Geiran OR, Bugge JF: Renal function after cardiopulmonary bypass surgery in patients with impaired renal function. A randomized study of the effect of nifedipine. Eur J Anaesthesiol 2008;25:319–325.
83.
Woo EB, Tang AT, el-Gamel A, et al: Dopamine therapy for patients at risk of renal dysfunction following cardiac surgery: science or fiction? Eur J Cardiothorac Surg 2002;22:106–111.
84.
Yallop KG, Sheppard SV, Smith DC: The effect of mannitol on renal function following cardio-pulmonary bypass in patients with normal pre-operative creatinine. Anaesthesia 2008;63:576–582.
85.
Yavuz S, Ayabakan N, Dilek K, Ozdemir A: Renal dose dopamine in open heart surgery. Does it protect renal tubular function? J Cardiovasc Surg 2002;43:25–30.
86.
Yavuz S, Ayabakan N, Goncu MT, Ozdemir IA: Effect of combined dopamine and diltiazem on renal function after cardiac surgery. Med Sci Monit 2002;8:P45–P50.
87.
Parikh CR, Garg AX: Acute kidney injury: Better biomarkers and beyond. Kidney Int 2008;73:801–803.
88.
Furnary AP, Wu Y, Hiratzka LF, Grunkemeier GL, Page US 3rd: Aprotinin does not increase the risk of renal failure in cardiac surgery patients. Circulation 2007;116:127–133.
89.
Mehta RL, Kellum JA, Shah SV, et al: Acute Kidney Injury Network: report of an initiative to improve acute kidney injury outcomes. Crit Care 2007;11:R31.
© 2010 S. Karger AG, Basel
2010
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.