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01-11-2011

Pharmacological therapies for the prevention of acute kidney injury following cardiac surgery: a systematic review

Authors: Nishith N. Patel, Chris A. Rogers, Gianni D. Angelini, Gavin J. Murphy

Published in: Heart Failure Reviews | Issue 6/2011

Abstract

Post-cardiac surgery acute kidney injury (AKI) is common and is associated with a significant increase in morbidity and mortality. We aimed to systematically review randomised trials that assessed the renoprotective utility of pharmacological agents in patients undergoing cardiac surgery. We searched PubMed, Embase and the Cochrane Central Register of Controlled Trials for randomised controlled trials comparing renoprotective pharmacological interventions with control in adult patients undergoing cardiac surgery with cardiopulmonary bypass. We extracted data for mortality, need for renal replacement therapy (RRT), incidence of AKI, and creatinine clearance at 24–48 h. About 49 randomised controlled trials involving 4605 patients were included. Pharmacological interventions included dopamine, fenoldopam, calcium channel antagonists, natriuretic peptides, diuretics, and N-acetylcysteine. Most trials were of poor quality, with small sample sizes, under-reporting of randomisation procedure, allocation concealment and method of blinding. No pharmacological intervention significantly reduced mortality. Fenoldopam and Atrial Natriuretic Peptide (ANP) reduced the need for renal replacement therapy by 5% (NNT 20, 95% CI 11.3, 83.0) and 3.5% (NNT 29, 95% CI 17.1, 84.4), respectively. Brain Natriuretic Peptide resulted in a 10% reduction in the incidence of AKI (NNT 11, 95% CI 6.2, 32.0). Dopamine caused a significant reduction in creatinine clearance (−4.26 ml/min, 95% CI −7.14, −1.39). The quality of studies that have assessed pharmacological renoprotective agents in cardiac surgery is generally poor. Fenoldopam, ANP and BNP show evidence of renoprotection. Randomised studies evaluating the effect of novel renoprotective agents that are powered to detect clinically relevant differences in outcomes are required.

Bellomo R, Ronco C, Kellum JA et al (2004) 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 8:R204–R212PubMedCrossRef

Rosner MH, Okusa MD (2006) Acute kidney injury associated with cardiac surgery. Clin J Am Soc Nephrol 1:19–32PubMedCrossRef

Karkouti K, Wijeysundera DN, Yau TM et al (2009) Acute kidney injury after cardiac surgery: focus on modifiable risk factors. Circulation 119:495–502PubMedCrossRef

Mangano CM, Diamondstone LS, Ramsay JG et al (1998) Renal dysfunction after myocardial revascularization: risk factors, adverse outcomes, and hospital resource utilization. The Multicenter Study of Perioperative Ischemia Research Group. Ann Intern Med 128:194–203PubMed

Thakar CV, Worley S, Arrigain S et al (2005) Influence of renal dysfunction on mortality after cardiac surgery: modifying effect of preoperative renal function. Kidney Int 67:1112–1119PubMedCrossRef

Thakar CV, Worley S, Arrigain S et al (2007) Improved survival in acute kidney injury after cardiac surgery. Am J Kidney Dis 50:703–711PubMedCrossRef

Jadad AR, Moore RA, Carroll D et al (1996) Assessing the quality of reports of randomized clinical trials: is blinding necessary? Control Clin Trials 17:1–12PubMedCrossRef

Higgins JPT (2008) GSe. Cochrane handbook for systematic reviews of interventions version 5.0.1 [updated September 2008]. The Cochrane Collaboration, Oxford

Moher D, Cook DJ, Eastwood S et al (1999) Improving the quality of reports of meta-analyses of randomised controlled trials: the QUOROM statement. Quality of reporting of meta-analyses. Lancet 354:1896–1900PubMedCrossRef

10.

Friedrich JO, Adhikari NK, Beyene J (2007) Inclusion of zero total event trials in meta-analyses maintains analytic consistency and incorporates all available data. BMC Med Res Methodol 7:5PubMedCrossRef

11.

Ranucci M, Soro G, Barzaghi N et al (2004) Fenoldopam prophylaxis of postoperative acute renal failure in high-risk cardiac surgery patients. Ann Thorac Surg 78:1332–1337PubMedCrossRef

12.

Morariu AM, Loef BG, Aarts LP et al (2005) Dexamethasone: benefit and prejudice for patients undergoing on-pump coronary artery bypass grafting: a study on myocardial, pulmonary, renal, intestinal, and hepatic injury. Chest 128:2677–2687PubMedCrossRef

13.

Haase M, Haase-Fielitz A, Ratnaike S et al (2008) N-acetylcysteine does not artifactually lower plasma creatinine concentration. Nephrol Dial Transplant 23:1581–1587PubMedCrossRef

14.

Gatot I, Abramov D, Tsodikov V et al (2004) Should we give prophylactic renal-dose dopamine after coronary artery bypass surgery? J Card Surg 19:128–133PubMedCrossRef

15.

Carcoana OV, Mathew JP, Davis E et al (2003) Mannitol and dopamine in patients undergoing cardiopulmonary bypass: a randomized clinical trial. Anesth Analg 97:1222–1229PubMedCrossRef

16.

Woo EB, Tang AT, el-Gamel A et al (2002) Dopamine therapy for patients at risk of renal dysfunction following cardiac surgery: science or fiction? Eur J Cardiothorac Surg 22:106–111PubMedCrossRef

17.

Yavuz S, Ayabakan N, Goncu MT et al (2002) Effect of combined dopamine and diltiazem on renal function after cardiac surgery. Med Sci Monit 8:PI45–PI50PubMed

18.

Yavuz S, Ayabakan N, Dilek K et al (2002) Renal dose dopamine in open heart surgery. Does it protect renal tubular function? J Cardiovasc Surg (Torino) 43:25–30

19.

Sumeray M, Robertson C, Lapsley M et al (2001) Low dose dopamine infusion reduces renal tubular injury following cardiopulmonary bypass surgery. J Nephrol 14:397–402PubMed

20.

Lassnigg A, Donner E, Grubhofer G et al (2000) Lack of renoprotective effects of dopamine and furosemide during cardiac surgery. J Am Soc Nephrol 11:97–104PubMed

21.

Tang AT, El-Gamel A, Keevil B et al (1999) The effect of ‘renal-dose’ dopamine on renal tubular function following cardiac surgery: assessed by measuring retinol binding protein (RBP). Eur J Cardiothorac Surg 15:717–721PubMedCrossRef

22.

Lema G, Urzua J, Jalil R et al (1998) Renal protection in patients undergoing cardiopulmonary bypass with preoperative abnormal renal function. Anesth Analg 86:3–8PubMed

23.

Myles PS, Buckland MR, Schenk NJ et al (1993) Effect of “renal-dose” dopamine on renal function following cardiac surgery. Anaesth Intensive Care 21:56–61PubMed

24.

Costa P, Ottino GM, Matani A et al (1990) Low-dose dopamine during cardiopulmonary bypass in patients with renal dysfunction. J Cardiothorac Anesth 4:469–473PubMedCrossRef

25.

Cogliati AA, Vellutini R, Nardini A et al (2007) Fenoldopam infusion for renal protection in high-risk cardiac surgery patients: a randomized clinical study. J Cardiothorac Vasc Anesth 21:847–850PubMedCrossRef

26.

Bove T, Landoni G, Calabro MG et al (2005) Renoprotective action of fenoldopam in high-risk patients undergoing cardiac surgery: a prospective, double-blind, randomized clinical trial. Circulation 111:3230–3235PubMedCrossRef

27.

Caimmi PP, Pagani L, Micalizzi E et al (2003) Fenoldopam for renal protection in patients undergoing cardiopulmonary bypass. J Cardiothorac Vasc Anesth 17:491–494PubMedCrossRef

28.

Halpenny M, Lakshmi S, O’Donnell A et al (2001) Fenoldopam: renal and splanchnic effects in patients undergoing coronary artery bypass grafting. Anaesthesia 56:953–960PubMedCrossRef

29.

Piper SN, Kumle B, Maleck WH et al (2003) Diltiazem may preserve renal tubular integrity after cardiac surgery. Can J Anaesth 50:285–292PubMedCrossRef

30.

Bergman AS, Odar-Cederlof I, Westman L et al (2002) Diltiazem infusion for renal protection in cardiac surgical patients with preexisting renal dysfunction. J Cardiothorac Vasc Anesth 16:294–299PubMedCrossRef

31.

Amano J, Suzuki A, Sunamori M et al (1995) Effect of calcium antagonist diltiazem on renal function in open heart surgery. Chest 107:1260–1265PubMedCrossRef

32.

Witczak BJ, Hartmann A, Geiran OR et al (2008) Renal function after cardiopulmonary bypass surgery in patients with impaired renal function. A randomized study of the effect of nifedipine. Eur J Anaesthesiol 25:319–325PubMedCrossRef

33.

Bertolissi M, Antonucci F, De Monte A et al (1996) Effects on renal function of a continuous infusion of nifedipine during cardiopulmonary bypass. J Cardiothorac Vasc Anesth 10:238–242PubMedCrossRef

34.

Sezai A, Hata M, Niino T et al (2009) Influence of continuous infusion of low-dose human atrial natriuretic peptide on renal function during cardiac surgery: a randomized controlled study. J Am Coll Cardiol 54:1058–1064PubMedCrossRef

35.

Izumi K, Eishi K, Yamachika S et al (2008) The efficacy of human atrial natriuretic peptide in patients with renal dysfunction undergoing cardiac surgery. Ann Thorac Cardiovasc Surg 14:294–302PubMed

36.

Sezai A, Hata M, Wakui S et al (2007) Efficacy of continuous low-dose hANP administration in patients undergoing emergent coronary artery bypass grafting for acute coronary syndrome. Circ J 71:1401–1407PubMedCrossRef

37.

Sezai A, Hata M, Wakui S et al (2006) Efficacy of low-dose continuous infusion of alpha-human atrial natriuretic peptide (hANP) during cardiac surgery: possibility of postoperative left ventricular remodeling effect. Circ J 70:1426–1431PubMedCrossRef

38.

Sward K, Valsson F, Odencrants P et al (2004) Recombinant human atrial natriuretic peptide in ischemic acute renal failure: a randomized placebo-controlled trial. Crit Care Med 32:1310–1315PubMedCrossRef

39.

Sezai A, Shiono M, Orime Y et al (2000) Low-dose continuous infusion of human atrial natriuretic peptide during and after cardiac surgery. Ann Thorac Surg 69:732–738PubMedCrossRef

40.

Hayashida N, Chihara S, Kashikie H et al (2000) Effects of intraoperative administration of atrial natriuretic peptide. Ann Thorac Surg 70:1319–1326PubMedCrossRef

41.

Bergman A, Odar-Cederlof I, Westman L et al (1996) Effects of human atrial natriuretic peptide in patients after coronary artery bypass surgery. J Cardiothorac Vasc Anesth 10:490–496PubMedCrossRef

42.

Ejaz AA, Martin TD, Johnson RJ et al (2009) Prophylactic nesiritide does not prevent dialysis or all-cause mortality in patients undergoing high-risk cardiac surgery. J Thorac Cardiovasc Surg 138:959–964PubMedCrossRef

43.

Chen HH, Sundt TM, Cook DJ et al (2007) 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 116:I134–I138PubMedCrossRef

44.

Mentzer RM Jr, Oz MC, Sladen RN et al (2007) Effects of perioperative nesiritide in patients with left ventricular dysfunction undergoing cardiac surgery:the NAPA trial. J Am Coll Cardiol 49:716–726PubMedCrossRef

45.

Kaya K, Oguz M, Akar AR et al (2007) 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 31:290–297PubMedCrossRef

46.

Boldt J, Brosch C, Lehmann A et al (2004) The prophylactic use of the beta-blocker esmolol in combination with phosphodiesterase III inhibitor enoximone in elderly cardiac surgery patients. Anesth Analg 99:1009–1017PubMedCrossRef

47.

Boldt J, Brosch C, Suttner S et al (2002) Prophylactic use of the phospodiesterase III inhibitor enoximone in elderly cardiac surgery patients: effect on hemodynamics, inflammation, and markers of organ function. Intensive Care Med 28:1462–1469PubMedCrossRef

48.

Abe K, Fujino Y, Sakakibara T (1993) The effect of prostaglandin E1 during cardiopulmonary bypass on renal function after cardiac surgery. Eur J Clin Pharmacol 45:217–220PubMedCrossRef

49.

Morgera S, Woydt R, Kern H et al (2002) Low-dose prostacyclin preserves renal function in high-risk patients after coronary bypass surgery. Crit Care Med 30:107–112PubMedCrossRef

50.

Mahesh B, Yim B, Robson D et al (2008) Does furosemide prevent renal dysfunction in high-risk cardiac surgical patients? Results of a double-blinded prospective randomised trial. Eur J Cardiothorac Surg 33:370–376PubMedCrossRef

51.

Smith MN, Best D, Sheppard SV et al (2008) The effect of mannitol on renal function after cardiopulmonary bypass in patients with established renal dysfunction. Anaesthesia 63:701–704PubMedCrossRef

52.

Yallop KG, Sheppard SV, Smith DC (2008) The effect of mannitol on renal function following cardio-pulmonary bypass in patients with normal pre-operative creatinine. Anaesthesia 63:576–582PubMedCrossRef

53.

Adabag AS, Ishani A, Koneswaran S et al (2008) Utility of N-acetylcysteine to prevent acute kidney injury after cardiac surgery: a randomized controlled trial. Am Heart J 155:1143–1149PubMedCrossRef

54.

Sisillo E, Ceriani R, Bortone F et al (2008) 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 36:81–86PubMedCrossRef

55.

Wijeysundera DN, Beattie WS, Rao V et al (2007) N-acetylcysteine for preventing acute kidney injury in cardiac surgery patients with pre-existing moderate renal insufficiency. Can J Anaesth 54:872–881PubMedCrossRef

56.

Haase M, Haase-Fielitz A, Bagshaw SM et al (2007) Phase II, randomized, controlled trial of high-dose N-acetylcysteine in high-risk cardiac surgery patients. Crit Care Med 35:1324–1331PubMedCrossRef

57.

Ristikankare A, Kuitunen T, Kuitunen A et al (2006) Lack of renoprotective effect of i.v. N-acetylcysteine in patients with chronic renal failure undergoing cardiac surgery. Br J Anaesth 97:611–616PubMedCrossRef

58.

Burns KE, Chu MW, Novick RJ et al (2005) Perioperative N-acetylcysteine to prevent renal dysfunction in high-risk patients undergoing cabg surgery: a randomized controlled trial. JAMA 294:342–350PubMedCrossRef

59.

Barr LF, Kolodner K (2008) N-acetylcysteine and fenoldopam protect the renal function of patients with chronic renal insufficiency undergoing cardiac surgery. Crit Care Med 36:1427–1435PubMedCrossRef

60.

El-Hamamsy I, Stevens LM, Carrier M et al (2007) Effect of intravenous N-acetylcysteine on outcomes after coronary artery bypass surgery: a randomized, double-blind, placebo-controlled clinical trial. J Thorac Cardiovasc Surg 133:7–12PubMedCrossRef

61.

Loef BG, Henning RH, Epema AH et al (2004) Effect of dexamethasone on perioperative renal function impairment during cardiac surgery with cardiopulmonary bypass. Br J Anaesth 93:793–798PubMedCrossRef

62.

McBride WT, Allen S, Gormley SM et al (2004) Methylprednisolone favourably alters plasma and urinary cytokine homeostasis and subclinical renal injury at cardiac surgery. Cytokine 27:81–89PubMedCrossRef

63.

Zacharias M, Gilmore IC, Herbison GP et al. (2005) Interventions for protecting renal function in the perioperative period. Cochrane Database Syst Rev: CD003590

64.

Friedrich JO, Adhikari N, Herridge MS et al (2005) Meta-analysis: low-dose dopamine increases urine output but does not prevent renal dysfunction or death. Ann Intern Med 142:510–524PubMed

65.

Landoni G, Biondi-Zoccai GG, Marino G et al (2008) Fenoldopam reduces the need for renal replacement therapy and in-hospital death in cardiovascular surgery: a meta-analysis. J Cardiothorac Vasc Anesth 22:27–33PubMedCrossRef

66.

Landoni G, Biondi-Zoccai GG, Tumlin JA et al (2007) Beneficial impact of fenoldopam in critically ill patients with or at risk for acute renal failure: a meta-analysis of randomized clinical trials. Am J Kidney Dis 49:56–68PubMedCrossRef

67.

Nigwekar SU, Navaneethan SD, Parikh CR et al (2008) Atrial natriuretic peptide for management of acute kidney injury: a systematic review and meta-analysis. Clin J Am Soc Nephrol 4(2):261–272PubMedCrossRef

68.

Chintala MS, Chiu PJ, Vemulapalli S et al (1993) Inhibition of endothelial derived relaxing factor (EDRF) aggravates ischemic acute renal failure in anesthetized rats. Naunyn Schmiedebergs Arch Pharmacol 348:305–310PubMedCrossRef

69.

Kurata H, Takaoka M, Kubo Y et al (2004) Nitric oxide protects against ischemic acute renal failure through the suppression of renal endothelin-1 overproduction. J Cardiovasc Pharmacol 44:S455–S458PubMedCrossRef

70.

Matsumura Y, Nishiura M, Deguchi S et al (1998) Protective effect of FK409, a spontaneous nitric oxide releaser, on ischemic acute renal failure in rats. J Pharmacol Exp Ther 287:1084–1091PubMed

71.

Goligorsky MS, Brodsky SV, Noiri E (2002) Nitric oxide in acute renal failure: NOS versus NOS. Kidney Int 61:855–861PubMedCrossRef

72.

Baker WL, Anglade MW, Baker EL et al (2009) Use of N-acetylcysteine to reduce post-cardiothoracic surgery complications: a meta-analysis. Eur J Cardiothorac Surg 35:521–527PubMedCrossRef

73.

Naughton F, Wijeysundera D, Karkouti K et al (2008) N-acetylcysteine to reduce renal failure after cardiac surgery: a systematic review and meta-analysis. Can J Anaesth 55:827–835PubMedCrossRef

74.

Nigwekar SU, Kandula P (2009) N-acetylcysteine in cardiovascular-surgery-associated renal failure: a meta-analysis. Ann Thorac Surg 87:139–147PubMedCrossRef

75.

Ho KM, Morgan DJ (2009) Meta-analysis of N-acetylcysteine to prevent acute renal failure after major surgery. Am J Kidney Dis 53:33–40PubMedCrossRef

76.

Zhu J, Yin R, Shao H et al (2007) N-acetylcysteine to ameliorate acute renal injury in a rat cardiopulmonary bypass model. J Thorac Cardiovasc Surg 133:696–703PubMedCrossRef

77.

DiMari J, Megyesi J, Udvarhelyi N et al (1997) N-acetyl cysteine ameliorates ischemic renal failure. Am J Physiol 272:F292–F298PubMed

78.

Decramer M, Rutten-van Molken M, Dekhuijzen PN et al (2005) Effects of N-acetylcysteine on outcomes in chronic obstructive pulmonary disease (Bronchitis Randomized on NAC Cost-Utility study, BRONCUS): a randomised placebo-controlled trial. Lancet 365:1552–1560PubMedCrossRef

79.

van Zandwijk N, Dalesio O, Pastorino U et al (2000) EUROSCAN, a randomized trial of vitamin A and N-acetylcysteine in patients with head and neck cancer or lung cancer. For the EUropean Organization for Research and Treatment of Cancer Head and Neck and Lung Cancer Cooperative Groups. J Natl Cancer Inst 92:977–986PubMedCrossRef

80.

Murphy GJ, Reeves BC, Rogers CA et al (2007) Increased mortality, postoperative morbidity, and cost after red blood cell transfusion in patients having cardiac surgery. Circulation 116:2544–2552PubMedCrossRef

81.

Haase M, Bellomo R, Haase-Fielitz A (2010) Novel biomarkers, oxidative stress, and the role of labile iron toxicity in cardiopulmonary bypass-associated acute kidney injury. J Am Coll Cardiol 55:2024–2033PubMedCrossRef

Title: Pharmacological therapies for the prevention of acute kidney injury following cardiac surgery: a systematic review
Authors: Nishith N. Patel
Chris A. Rogers
Gianni D. Angelini
Gavin J. Murphy
Publication date: 01-11-2011
Publisher: Springer US
Published in: Heart Failure Reviews / Issue 6/2011
Print ISSN: 1382-4147
Electronic ISSN: 1573-7322
DOI: https://doi.org/10.1007/s10741-011-9235-5

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