Skip to main content
SpringerLink
Log in

Effect of atorvastatin on the incidence of acute kidney injury following valvular heart surgery: a randomized, placebo-controlled trial

  • Original
  • Published:
Intensive Care Medicine Aims and scope Submit manuscript

Abstract

Purpose

Statins, 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors have the potential to reduce acute kidney injury (AKI) after cardiac surgery through their pleiotropic properties. Here we studied the preventive effect of atorvastatin on AKI after valvular heart surgery.

Methods

Two-hundred statin-naïve patients were randomly allocated to receive either statin or placebo. Atorvastatin was administered orally to the statin group according to a dosage schedule (80 mg single dose on the evening prior to surgery; 40 mg on the morning of surgery; three further doses of 40 mg on the evenings of postoperative days 0, 1, and 2). AKI incidence was assessed during the first 48 postoperative hours on the basis of Acute Kidney Injury Network criteria.

Results

The incidence of AKI was similar in the statin and control groups (21 vs. 26 %, respectively, p = 0.404). Biomarkers of renal injury including plasma neutrophil gelatinase-associated lipocalin and interleukin-18 were also similar between the groups. The statin group required significantly less norepinephrine and vasopressin during surgery, and fewer patients in the statin group required vasopressin. There were no significant differences in postoperative outcomes.

Conclusions

Acute perioperative statin treatment was not associated with a lower incidence of AKI or improved clinical outcome in patients undergoing valvular heart surgery. (ClinicalTrials.gov NCT01909739).

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1

Similar content being viewed by others

References

  1. Parida S, Badhe AS (2013) Cardiac surgery-associated acute kidney injury. J Anesth 27:433–446

    Article  PubMed  Google Scholar 

  2. Tuttle KR, Worrall NK, Dahlstrom LR, Nandagopal R, Kausz AT, Davis CL (2003) Predictors of ARF after cardiac surgical procedures. Am J Kidney Dis 41:76–83

    Article  PubMed  Google Scholar 

  3. Druml W, Lenz K, Laggner AN (2015) Our paper 20 years later: from acute renal failure to acute kidney injury—the metamorphosis of a syndrome. Intensive Care Med 41:1941–1949

    Article  PubMed  Google Scholar 

  4. Hoste EA, Bagshaw SM, Bellomo R, Cely CM, Colman R, Cruz DN, Edipidis K, Forni LG, Gomersall CD, Govil D, Honore PM, Joannes-Boyau O, Joannidis M, Korhonen AM, Lavrentieva A, Mehta RL, Palevsky P, Roessler E, Ronco C, Uchino S, Vazquez JA, Vidal Andrade E, Webb S, Kellum JA (2015) Epidemiology of acute kidney injury in critically ill patients: the multinational AKI-EPI study. Intensive Care Med 41:1411–1423

    Article  PubMed  Google Scholar 

  5. Shishehbor MH, Brennan ML, Aviles RJ, Fu X, Penn MS, Sprecher DL, Hazen SL (2003) Statins promote potent systemic antioxidant effects through specific inflammatory pathways. Circulation 108:426–431

    Article  CAS  PubMed  Google Scholar 

  6. Patti G, Ricottini E, Nusca A, Colonna G, Pasceri V, D’Ambrosio A, Montinaro A, Di Sciascio G (2011) Short-term, high-dose atorvastatin pretreatment to prevent contrast-induced nephropathy in patients with acute coronary syndromes undergoing percutaneous coronary intervention (from the ARMYDA-CIN [atorvastatin for reduction of myocardial damage during angioplasty–contrast-induced nephropathy] trial. Am J Cardiol 108:1–7

    Article  CAS  PubMed  Google Scholar 

  7. Patti G, Pasceri V, Colonna G, Miglionico M, Fischetti D, Sardella G, Montinaro A, Di Sciascio G (2007) Atorvastatin pretreatment improves outcomes in patients with acute coronary syndromes undergoing early percutaneous coronary intervention: results of the ARMYDA-ACS randomized trial. J Am Coll Cardiol 49:1272–1278

    Article  CAS  PubMed  Google Scholar 

  8. Singh N, Lee JZ, Huang JJ, Low SW, Howe C, Pandit A, Suryanarayana P, Lee KS (2014) Benefit of statin pretreatment in prevention of contrast-induced nephropathy in different adult patient population: systematic review and meta-analysis. Open Heart 1:e000127

    Article  PubMed  PubMed Central  Google Scholar 

  9. Liu Y, Su Q, Li L (2013) Efficacy of short-term high-dose atorvastatin pretreatment in patients with acute coronary syndrome undergoing percutaneous coronary intervention: a meta-analysis of nine randomized controlled trials. Clin Cardiol 36:E41–E48

    Article  PubMed  Google Scholar 

  10. Prowle JR, Calzavacca P, Licari E, Ligabo EV, Echeverri JE, Haase M, Haase-Fielitz A, Bagshaw SM, Devarajan P, Bellomo R (2012) Pilot double-blind, randomized controlled trial of short-term atorvastatin for prevention of acute kidney injury after cardiac surgery. Nephrology (Carlton) 17:215–224

    Article  CAS  Google Scholar 

  11. Layton JB, Kshirsagar AV, Simpson RJ Jr, Pate V, Jonsson Funk M, Sturmer T, Brookhart MA (2013) Effect of statin use on acute kidney injury risk following coronary artery bypass grafting. Am J Cardiol 111:823–828

    Article  CAS  PubMed  Google Scholar 

  12. Molnar AO, Parikh CR, Coca SG, Thiessen-Philbrook H, Koyner JL, Shlipak MG, Myers ML, Garg AX, TRIBE-AKI Consortium (2014) Association between preoperative statin use and acute kidney injury biomarkers in cardiac surgical procedures. Ann Thorac Surg 97:2081–2087

    Article  PubMed  PubMed Central  Google Scholar 

  13. Billings FT, Hendricks PA, Schildcrout JS, Shi Y, Petracek MR, Byrne JG, Brown NJ (2016) High-dose perioperative atorvastatin and acute kidney injury following cardiac surgery: a randomized clinical trial. JAMA 315:877–888

    Article  PubMed  PubMed Central  Google Scholar 

  14. Levey AS, Bosch JP, Lewis JB, Greene T, Rogers N, Roth D (1999) A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation. Modification of diet in renal disease study group. Ann Intern Med 130:461–470

    Article  CAS  PubMed  Google Scholar 

  15. Mehta RL, Kellum JA, Shah SV, Molitoris BA, Ronco C, Warnock DG, Levin A, Acute Kidney Injury Network (2007) Acute kidney injury network: report of an initiative to improve outcomes in acute kidney injury. Crit Care 11:R31

    Article  PubMed  PubMed Central  Google Scholar 

  16. Ohman EM, Bhatt DL, Steg PG, Goto S, Hirsch AT, Liau CS, Mas JL, Richard AJ, Rother J, Wilson PW, REACH Registry Investigators (2006) The REduction of Atherothrombosis for Continued Health (REACH) Registry: an international, prospective, observational investigation in subjects at risk for atherothrombotic events-study design. Am Heart J 151:786.e1–10

    Article  Google Scholar 

  17. Thakar CV, Arrigain S, Worley S, Yared JP, Paganini EP (2005) A clinical score to predict acute renal failure after cardiac surgery. J Am Soc Nephrol 16:162–168

    Article  PubMed  Google Scholar 

  18. Chalasani N (2005) Statins and hepatotoxicity: focus on patients with fatty liver. Hepatology 41:690–695

    Article  CAS  PubMed  Google Scholar 

  19. Cho JS, Shim JK, Soh S, Kim MK, Kwak YL (2016) Perioperative dexmedetomidine reduces the incidence and severity of acute kidney injury following valvular heart surgery. Kidney Int 89:693–700

    Article  CAS  PubMed  Google Scholar 

  20. Yoo YC, Shim JK, Kim JC, Jo YY, Lee JH, Kwak YL (2011) Effect of single recombinant human erythropoietin injection on transfusion requirements in preoperatively anemic patients undergoing valvular heart surgery. Anesthesiology 115:929–937

    Article  CAS  PubMed  Google Scholar 

  21. Antonelli M, Bonten M, Chastre J, Citerio G, Conti G, Curtis JR, De Backer D, Hedenstierna G, Joannidis M, Macrae D, Mancebo J, Maggiore SM, Mebazaa A, Preiser JC, Rocco P, Timsit JF, Wernerman J, Zhang H (2012) Year in review in Intensive Care Medicine 2011: I. Nephrology, epidemiology, nutrition and therapeutics, neurology, ethical and legal issues, experimentals. Intensive Care Med 38:192–209

    Article  PubMed  PubMed Central  Google Scholar 

  22. Colhoun HM, Betteridge DJ, Durrington PN, Hitman GA, Neil HA, Livingstone SJ, Thomason MJ, Mackness MI, Charlton-Menys V, Fuller JH, investigators C (2004) Primary prevention of cardiovascular disease with atorvastatin in type 2 diabetes in the Collaborative Atorvastatin Diabetes Study (CARDS): multicentre randomised placebo-controlled trial. Lancet 364:685–696

    Article  CAS  PubMed  Google Scholar 

  23. Epstein M, Campese VM (2005) Pleiotropic effects of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors on renal function. Am J Kidney Dis 45:2–14

    Article  CAS  PubMed  Google Scholar 

  24. Han Y, Zhu G, Han L, Hou F, Huang W, Liu H, Gan J, Jiang T, Li X, Wang W, Ding S, Jia S, Shen W, Wang D, Sun L, Qiu J, Wang X, Li Y, Deng J, Li J, Xu K, Xu B, Mehran R, Huo Y (2014) Short-term rosuvastatin therapy for prevention of contrast-induced acute kidney injury in patients with diabetes and chronic kidney disease. J Am Coll Cardiol 63:62–70

    Article  CAS  PubMed  Google Scholar 

  25. Lewicki M, Ng I, Schneider AG (2015) HMG CoA reductase inhibitors (statins) for preventing acute kidney injury after surgical procedures requiring cardiac bypass. Cochrane Database Syst Rev 3:CD010480

    PubMed  Google Scholar 

  26. García Rodríguez LA, Herings R, Johansson S (2010) Use of multiple international healthcare databases for the detection of rare drug-associated outcomes: a pharmacoepidemiological programme comparing rosuvastatin with other marketed statins. Pharmacoepidemiol Drug Saf 19:1218–1224

    Article  PubMed  Google Scholar 

  27. Florens E, Salvi S, Peynet J, Elbim C, Mallat Z, Bel A, Nguyen A, Tedgui A, Pasquier C, Menasche P (2001) Can statins reduce the inflammatory response to cardiopulmonary bypass? A clinical study. J Card Surg 16:232–239

    Article  CAS  PubMed  Google Scholar 

  28. Bustos C, Hernandez-Presa MA, Ortego M, Tunon J, Ortega L, Perez F, Diaz C, Hernandez G, Egido J (1998) HMG-CoA reductase inhibition by atorvastatin reduces neointimal inflammation in a rabbit model of atherosclerosis. J Am Coll Cardiol 32:2057–2064

    Article  CAS  PubMed  Google Scholar 

  29. Adabag AS, Ishani A, Koneswaran S, Johnson DJ, Kelly RF, Ward HB, McFalls EO, Bloomfield HE, Chandrashekhar Y (2008) Utility of N-acetylcysteine to prevent acute kidney injury after cardiac surgery: a randomized controlled trial. Am Heart J 155:1143–1149

    Article  CAS  PubMed  Google Scholar 

  30. Haase M, Haase-Fielitz A, Plass M, Kuppe H, Hetzer R, Hannon C, Murray PT, Bailey MJ, Bellomo R, Bagshaw SM (2013) Prophylactic perioperative sodium bicarbonate to prevent acute kidney injury following open heart surgery: a multicenter double-blinded randomized controlled trial. PLoS Med 10:e1001426

    Article  PubMed  PubMed Central  Google Scholar 

  31. Marenzi G, Assanelli E, Marana I, Lauri G, Campodonico J, Grazi M, De Metrio M, Galli S, Fabbiocchi F, Montorsi P, Veglia F, Bartorelli AL (2006) N-acetylcysteine and contrast-induced nephropathy in primary angioplasty. N Engl J Med 354:2773–2782

    Article  CAS  PubMed  Google Scholar 

  32. Jang JS, Jin HY, Seo JS, Yang TH, Kim DK, Kim TH, Urm SH, Kim DS, Kim DK, Seol SH, Kim DI, Cho KI, Kim BH, Park YH, Je HG, Ahn JM, Kim WJ, Lee JY, Lee SW (2012) Sodium bicarbonate therapy for the prevention of contrast-induced acute kidney injury—a systematic review and meta-analysis. Circ J 76:2255–2265

    Article  CAS  PubMed  Google Scholar 

  33. Singh I, Rajagopalan S, Srinivasan A, Achuthan S, Dhamija P, Hota D, Chakrabarti A (2013) Preoperative statin therapy is associated with lower requirement of renal replacement therapy in patients undergoing cardiac surgery: a meta-analysis of observational studies. Interact CardioVasc Thorac Surg 17:345–352

    Article  PubMed  PubMed Central  Google Scholar 

  34. Borger MA, Seeburger J, Walther T, Borger F, Rastan A, Doenst T, Mohr FW (2010) Effect of preoperative statin therapy on patients undergoing isolated and combined valvular heart surgery. Ann Thorac Surg 89:773–780

    Article  PubMed  Google Scholar 

  35. Allou N, Augustin P, Dufour G, Tini L, Ibrahim H, Dilly MP, Montravers P, Wallace J, Provenchere S, Philip I (2010) Preoperative statin treatment is associated with reduced postoperative mortality after isolated cardiac valve surgery in high-risk patients. J Cardiothorac Vasc Anesth 24:921–926

    Article  CAS  PubMed  Google Scholar 

  36. Leslie JA, Meldrum KK (2008) The role of interleukin-18 in renal injury. J Surg Res 145:170–175

    Article  CAS  PubMed  Google Scholar 

  37. Kumar RA, Cann C, Hall JE, Sudheer PS, Wilkes AR (2007) Predictive value of IL-18 and SC5b-9 for neurocognitive dysfunction after cardiopulmonary bypass. Br J Anaesth 98:317–322

    Article  CAS  PubMed  Google Scholar 

  38. Liu Y, Jiang H, Liu W, Shang H, Tang Y, Zhu R, Li B (2010) Effects of fluvastatin therapy on serum interleukin-18 and interleukin-10 levels in patients with acute coronary syndrome. Acta Cardiol 65:285–289

    Article  PubMed  Google Scholar 

  39. Mansur A, Steinau M, Popov AF, Ghadimi M, Beissbarth T, Bauer M, Hinz J (2015) Impact of statin therapy on mortality in patients with sepsis-associated acute respiratory distress syndrome (ARDS) depends on ARDS severity: a prospective observational cohort study. BMC Med 13:128

    Article  PubMed  PubMed Central  Google Scholar 

  40. Giusti-Paiva A, Martinez MR, Felix JV, da Rocha MJ, Carnio EC, Elias LL, Antunes-Rodrigues J (2004) Simvastatin decreases nitric oxide overproduction and reverts the impaired vascular responsiveness induced by endotoxic shock in rats. Shock 21:271–275

    Article  CAS  PubMed  Google Scholar 

  41. Kandasamy K, Prawez S, Choudhury S, More AS, Ahanger AA, Singh TU, Parida S, Mishra SK (2011) Atorvastatin prevents vascular hyporeactivity to norepinephrine in sepsis: role of nitric oxide and alpha(1)-adrenoceptor mRNA expression. Shock 36:76–82

    Article  CAS  PubMed  Google Scholar 

  42. Ostermann M, Joannidis M (2015) Biomarkers for AKI improve clinical practice: no. Intensive Care Med 41:618–622

    Article  PubMed  Google Scholar 

  43. Legrand M, Darmon M (2015) Biomarkers for AKI improve clinical practice: yes. Intensive Care Med 41:615–617

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

No financial support.

Author information

Authors and Affiliations

  1. Department of Anesthesiology and Pain Medicine, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Republic of Korea

    Jin Ha Park, Jae-Kwang Shim, Jong-Wook Song, Sarah Soh & Young-Lan Kwak

  2. Anesthesia and Pain Research Institute, Yonsei Cardiovascular Research Institute, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemungu, Seoul, 03722, Republic of Korea

    Jae-Kwang Shim, Jong-Wook Song & Young-Lan Kwak

Authors
  1. Jin Ha Park
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jae-Kwang Shim
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jong-Wook Song
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Sarah Soh
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Young-Lan Kwak
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Young-Lan Kwak.

Ethics declarations

Funding

None.

Conflicts of interest

The authors declare that they have no conflict of list.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards.

Additional information

Take-home message: The effect of statin in ameliorating acute kidney injury induced by valvular heart surgery with cardiopulmonary bypass was studied. Acute perioperative statin treatment was not associated with the reduction of incidence of acute kidney injury.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Park, J.H., Shim, JK., Song, JW. et al. Effect of atorvastatin on the incidence of acute kidney injury following valvular heart surgery: a randomized, placebo-controlled trial. Intensive Care Med 42, 1398–1407 (2016). https://doi.org/10.1007/s00134-016-4358-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00134-016-4358-8

Keywords

Search

Navigation