Pediatric Nephrology

, Volume 28, Issue 2, pp 207–217

Acute kidney injury clinical trial design: old problems, new strategies

Review

Abstract

Apart from supportive dialysis there are no universally accepted interventions in acute kidney injury (AKI). We have summarized the outcomes of all published randomized, placebo-controlled studies of non-dialysis treatment of AKI. Forty-nine trials were identified, only one of which was in a paediatric population. Sixteen trials had positive outcomes; these trials are not comparable in terms of methodology used or outcomes assessed, and they share many of the problems of the negative trials. We discuss the flaws in clinical trial design that have contributed to poor or uncertain outcomes and propose minimum requirements for future trials. In particular, future trials should incorporate biomarkers specific to the etiology of the AKI, and treatment should match the phase of injury.

Keywords

Biomarkers Acute kidney injury Phase-specific renal injury Early intervention Late intervention 

References

  1. 1.
    Jo S-K, Rosner MH, Okusa MD (2007) Pharmacologic treatment of acute kidney injury: why drugs haven't worked and what is on the horizon. Clin J Am Soc Nephrol 2:356–365CrossRefPubMedGoogle Scholar
  2. 2.
    Pickering JW, Ralib AM, Nejat M, Endre ZH (2011) New considerations in the design of clinical trials of acute kidney injury. Clin Invest 1:637–650CrossRefGoogle Scholar
  3. 3.
    Palmer SC, Sciancalepore M, Strippoli GFM (2011) Trial quality in nephrology: how are we measuring up? Am J Kid Dis 58:335–337CrossRefPubMedGoogle Scholar
  4. 4.
    Endre ZH, Pickering JW (2010) Outcome definitions in non-dialysis intervention and prevention trials in acute kidney injury (AKI). Nephrol Dial Transplant 25:107–118CrossRefPubMedGoogle Scholar
  5. 5.
    Song YR, Lee T, You SJ, Chin HJ, Chae D-W, Cheong L, Park K-H, Han S, Kim J-H, Na KY (2009) Prevention of acute kidney injury by erythropoietin in patients undergoing coronary artery bypass grafting: a pilot study. Am J Nephrol 30:253–260CrossRefPubMedGoogle Scholar
  6. 6.
    Ejaz AA, Martin TD, Johnson RJ, Winterstein AG, Klodell CT, Hess PJ, Ali AK, Whidden EM, Staples NL, Alexander JA, House-Fancher MA, Beaver TM (2009) Prophylactic nesiritide does not prevent dialysis or all-cause mortality in patients undergoing high-risk cardiac surgery. J Thorac Cardiovasc Surg 138:959–964CrossRefPubMedGoogle Scholar
  7. 7.
    Mentzer RM, Oz MC, Sladen RN, Graeve AH, Hebeler RF Jr, Luber JM Jr, Smedira NG, NAPA Investigators (2007) Effects of perioperative nesiritide in patients with left ventricular dysfunction undergoing cardiac surgery:the NAPA Trial. J Am Coll Cardiol 49:716–726CrossRefPubMedGoogle Scholar
  8. 8.
    Sezai A, Hata M, Niino T, Yoshitake I, Unosawa S, Wakui S, Osaka S, Takayama T, Kasamaki Y, Hirayama A, Minami K (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 54:1058–1064CrossRefPubMedGoogle Scholar
  9. 9.
    Ranucci M, Soro G, Barzaghi N, Locatelli A, Giordano G, Vavassori A, Manzato A, Melchiorri C, Bove T, Juliano G, Uslenghi MF (2004) Fenoldopam prophylaxis of postoperative acute renal failure in high-risk cardiac surgery patients. Ann Thorac Surg 78:1332–1337CrossRefPubMedGoogle Scholar
  10. 10.
    Morelli A, Ricci Z, Bellomo R, Ronco C, Rocco M, Conti G, de Gaetano A, Picchini U, Orechhioni A, Portieri M, Coluzzi F, Porzi P, Serio P, Bruno A, Pietropaoli P (2005) Prophylactic fenoldopam for renal protection in sepsis: a randomized, double-blind, placebo-controlled pilot trial. Crit Care Med 33:2451–2456CrossRefPubMedGoogle Scholar
  11. 11.
    van Valenberg PL, Hoitsma AJ, Tiggeler RG, Berden JH, van Lier HJ, Koene RA (1987) Mannitol as an indispensable constituent of an intraoperative hydration protocol for the prevention of acute renal failure after renal cadaveric transplantation. Transplantation 44:784–788CrossRefPubMedGoogle Scholar
  12. 12.
    Zimmerman RF, Ezeanuna PU, Kane JC, Cleland CD, Kempananjappa TJ, Lucas FL, Kramer RS (2011) Ischemic preconditioning at a remote site prevents acute kidney injury in patients following cardiac surgery. Kidney Int 80:861–867CrossRefPubMedGoogle Scholar
  13. 13.
    Akamatsu N, Sugawara Y, Tamura S, Kaneko J, Togashi J, Kishi T, Imamura H, Kokudo N, Makuuchi M (2005) Prevention of renal impairment by continuous infusion of human atrial natriuretic peptide after liver transplantation. Transplantation 80:1093–1098CrossRefPubMedGoogle Scholar
  14. 14.
    Cogliati AA, Vellutini R, Nardini A, Urovi S, Hamdan M, Landoni G, Guelfi P (2007) Fenoldopam infusion for renal protection in high-risk cardiac surgery patients: a randomized clinical study. J Cardiothorac Vasc Anesth 21:847–850CrossRefPubMedGoogle Scholar
  15. 15.
    Halpenny M, Lakshmi S, O'Donnell A, O'Callaghan-Enright S, Shorten G (2001) Fenoldopam: renal and splanchnic effects in patients undergoing coronary artery bypass grafting. Anaesthesia 56:953–960CrossRefPubMedGoogle Scholar
  16. 16.
    Kaya K, Oğuz M, Akar AR, Durdu S, Aslan A, Ertuk S, Tasoz R, Ozyurda U (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 31:290–297CrossRefPubMedGoogle Scholar
  17. 17.
    Franklin SC, Moulton M, Sicard GA, Hammerman MR, Miller SB (1997) Insulin-like growth factor I preserves renal function postoperatively. Am J Physiol 272:F257–F259PubMedGoogle Scholar
  18. 18.
    Heemskerk S, Masereeuw R, Moesker O, Bouw MPWJM, van der Hoeven JG, Peters WH, Russel FG, Pickkers P, APSEP Study Group (2009) Alkaline phosphatase treatment improves renal function in severe sepsis or septic shock patients. Crit Care Med 37:417–423CrossRefPubMedGoogle Scholar
  19. 19.
    Swärd K, Valsson F, Odencrants P, Samuelsson O, Ricksten S-E (2004) Recombinant human atrial natriuretic peptide in ischemic acute renal failure: a randomized placebo-controlled trial. Crit Care Med 32:1310–1315CrossRefPubMedGoogle Scholar
  20. 20.
    Givertz MM, Massie BM, Fields TK, Pearson LL, Dittrich HC, CK-201 and CKI-202 Investigators (2007) The effects of KW-3902, an adenosine A1-receptor antagonist, on diuresis and renal function in patients with acute decompensated heart failure and renal impairment or diuretic resistance. J Am Coll Cardiol 50:1551–1560CrossRefPubMedGoogle Scholar
  21. 21.
    Massie BM, O'Connor CM, Metra M, Ponikowski P, Teerlink JR, Cotter G, Weatherley BD, Cleland JGF, Givertz MM, Voors A, DeLucca P, Mansoor GA, Salerno CM, Bloomfield DM, Dittrich HC, PROTECT Investigators and Committees (2010) Rolofylline, an adenosine A1-receptor antagonist, in acute heart failure. N Engl J Med 363:1419–1428CrossRefPubMedGoogle Scholar
  22. 22.
    O'Donnell JL, Smyth D, Frampton C (2005) Prioritizing health-care funding. Int Med J 35:409–412CrossRefGoogle Scholar
  23. 23.
    Bonventre JV, Yang L (2011) Cellular pathophysiology of ischemic acute kidney injury. J Clin Invest 121:4210–4221CrossRefPubMedGoogle Scholar
  24. 24.
    Endre ZH, Pickering JW, Walker RJ (2011) Clearance and beyond: the complementary roles of GFR measurement and injury biomarkers in acute kidney injury (AKI). Am J Physiol Renal Physiol 301:F697–F707CrossRefPubMedGoogle Scholar
  25. 25.
    Heyman SN, Rosenberger C, Rosen S (2010) Experimental ischemia–reperfusion: biases and myths—the proximal vs. distal hypoxic tubular injury debate revisited. Kidney Int 77:9–16CrossRefPubMedGoogle Scholar
  26. 26.
    Jacobs R, Honore PM, Joannes-Boyau O, Boer W, De Regt J, De Waele E, Collin V, Spapen HD (2011) Septic acute kidney injury: the culprit is inflammatory apoptosis rather than ischemic necrosis. Blood Purif 32:262–265CrossRefPubMedGoogle Scholar
  27. 27.
    Pickering JW, Frampton CM, Endre ZH (2009) Evaluation of trial outcomes in acute kidney injury by creatinine modeling. Clin J Am Soc Nephrol 4:1705–1715CrossRefPubMedGoogle Scholar
  28. 28.
    Ioannidis J (2005) Why most published research findings are false. PLoS Med 2:696–701Google Scholar
  29. 29.
    Deo A, Schmid CH, Earley A, Lau J, Uhlig K (2011) Loss to analysis in randomized controlled trials in CKD. Am J Kidney Dis 58:349–355CrossRefPubMedGoogle Scholar
  30. 30.
    Star R (2001) Design issues for clinical trials in acute renal failure. Blood Purif 19:233–237CrossRefPubMedGoogle Scholar
  31. 31.
    Bellomo R, Ronco C, Kellum JA, Mehta RL, Palevsky PM, Acute Dialysis Quality Initiative Workgroup (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–R212CrossRefPubMedGoogle Scholar
  32. 32.
    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:R31CrossRefPubMedGoogle Scholar
  33. 33.
    KDIGO (Kidney Disease: Improving Global Outcomes) (2012) Section 2: AKI definition. Kidney Int Supp 2:19–36CrossRefGoogle Scholar
  34. 34.
    Coller FA, Maddock WG (1935) A study of dehydration in humans. Ann Surg 102:947–960CrossRefPubMedGoogle Scholar
  35. 35.
    Nejat M, Pickering JW, Devarajan P, Bonventre JV, Edelstein C, Walker RJ, Endre ZH (2012) Some acute kidney injury biomarkers are increased in pre-renal AKI. Kidney Int. doi:10.1038/ki.2012.23
  36. 36.
    Bellomo R, Bagshaw SM, Langenberg C, Ronco C (2007) Pre-renal azotemia: a flawed paradigm in critically ill septic patients? Contrib Nephrol 156:1–9CrossRefPubMedGoogle Scholar
  37. 37.
    Kellum JA, Ronco C, Vincent JL (2011) Unveiling current controversies in acute kidney injury. Contrib Nephrol 174:1–3CrossRefPubMedGoogle Scholar
  38. 38.
    Mishra J, Dent CL, Tarabishi R, Mitsnefes MM, Ma Q, Kelly C, Ruff SM, Zahedi K, Shao M, Bean J, Mori K, Barasch JM, Devarajan P (2005) Neutrophil gelatinase-associated lipocalin (NGAL) as a biomarker for acute renal injury after cardiac surgery. Lancet 365:1231–1238CrossRefPubMedGoogle Scholar
  39. 39.
    Endre ZH, Walker RJ, Pickering JW, Shaw GM, Frampton CM, Henderson SJ, Hutchison R, Mehrtens JE, Robinson JM, Schollum JBW, Westhuyzen J, Celi LA, McGinley RJ, Campbell IJ, George PM (2010) Early intervention with erythropoietin does not affect the outcome of acute kidney injury (the EARLYARF trial). Kidney Int 77:1020–1030CrossRefPubMedGoogle Scholar
  40. 40.
    Allgren RL, Marbury TC, Rahman SN, Weisberg LS, Fenves AZ, Lafayette RA, Sweet RM, Center FC, Kurnik BR, Conger JD, Sayegh MH (1997) Anaritide in acute tubular necrosis. Auriculin Anaritide Acute Renal Failure Study Group. N Engl J Med 336:828–834CrossRefPubMedGoogle Scholar
  41. 41.
    Johnson DW, Pat B, Vesey DA, Guan Z, Endre ZH, Gobe GC (2006) Delayed administration of darbepoetin or erythropoietin protects against ischemic acute renal injury and failure. Kidney Int 69:1806–1813CrossRefPubMedGoogle Scholar
  42. 42.
    Gil H-W, Yang J-O, Lee E-Y, Hong S-Y (2009) Clinical implication of urinary neutrophil gelatinase-associated lipocalin and kidney injury molecule-1 in patients with acute paraquat intoxication. Clin Toxicol 47:870–875CrossRefGoogle Scholar
  43. 43.
    Gaspari F, Cravedi P, Mandalà M, Perico N, de Leon FR, Stucci N, Ferrari S, Labianca R, Remuzzi G, Ruggenenti P (2010) Predicting cisplatin-induced acute kidney injury by urinary neutrophil gelatinase-associated lipocalin excretion: a pilot prospective case–control study. Nephron Clin Pract 115:c154–c160CrossRefPubMedGoogle Scholar
  44. 44.
    Mcilroy DR, Wagener G, Lee HT (2010) Neutrophil gelatinase-associated lipocalin and acute kidney injury after cardiac surgery: the effect of baseline renal function on diagnostic performance. Clin J Am Soc Nephrol 5:211–219CrossRefPubMedGoogle Scholar
  45. 45.
    Endre ZH, Pickering JW, Walker RJ, Devarajan P, Edelstein CL, Bonventre JV, Frampton CM, Bennett MR, Ma Q, Sabbisetti VS, Vaidya VS, Walcher AM, Shaw GM, Henderson SJ, Nejat M, Schollum JBW, George PM (2011) Improved performance of urinary biomarkers of acute kidney injury in the critically ill by stratification for injury duration and baseline renal function. Kidney Int 79:1119–1130CrossRefPubMedGoogle Scholar
  46. 46.
    Lipcsey M, Bellomo R (2011) Septic acute kidney injury: hemodynamic syndrome, inflammatory disorder, or both? Crit Care 15:1008CrossRefPubMedGoogle Scholar
  47. 47.
    Pickering JW, Endre ZH (2010) Back-calculating baseline creatinine with MDRD misclassifies acute kidney injury in the intensive care unit. Clin J Am Soc Nephrol 5:1165–1173CrossRefPubMedGoogle Scholar
  48. 48.
    Ralib AM, Pickering JW, Shaw GM, Devarajan P, Edelstein CL, Bonventre JV, Endre ZH (2012) Test characteristics of urinary biomarkers depend on quantitation method in acute kidney injury. J Am Soc Nephrol 23:322–333CrossRefPubMedGoogle Scholar
  49. 49.
    Cruz DN, de Geus HR, Bagshaw SM (2011) Biomarker strategies to predict need for renal replacement therapy in acute kidney injury. Semin Dial 24:124–131CrossRefPubMedGoogle Scholar
  50. 50.
    Nejat M, Pickering JW, Walker RJ, Westhuyzen J, Shaw GM, Frampton CM, Endre ZH (2010) Urinary cystatin C is diagnostic of acute kidney injury and sepsis, and predicts mortality in the intensive care unit. Crit Care 14:R85CrossRefPubMedGoogle Scholar
  51. 51.
    Kümpers P, Hafer C, Lukasz A, Lichtinghagen R, Brand K, Filser D, Faulhaber-Walter R, Kielstein JT (2010) Serum neutrophil gelatinase-associated lipocalin at inception of renal replacement therapy predicts survival in critically ill patients with acute kidney injury. Crit Care 14:R9CrossRefPubMedGoogle Scholar
  52. 52.
    Haase M, Devarajan P, Haase-Fielitz A, Bellomo R, Cruz DN, Wagener G, Krawczeski CD, Koyner JL, Murray P, Zappitelli M, Goldstein SL, Makris K, Ronco C, Martensson J, Martling C-R, Venge P, Siew E, Ware LB, Ilizler TA, Mertens PR (2011) The outcome of neutrophil gelatinase-associated lipocalin-positive subclinical acute kidney injury a multicenter pooled analysis of prospective studies. J Am Coll Cardiol 57:1752–1761CrossRefPubMedGoogle Scholar
  53. 53.
    Ozer JS, Dieterle F, Troth S, Perentes E, Cordier A, Verdes P, Staedtler F, Mahl A, Grenet O, Roth DR, Whal D, Legay F, Holder D, Erdos Z, Vlaskova K, Jin H, Yu Y, Muniappa N, Forest T, Clouse HK, Reynolds S, Bailey WJ, Thudium T, Toper MJ, Skopek TR, Sina JF, Glaab WE, Vonderscher J, Maurer G, Chibout S-D, Sistare FD, Gerhold DL (2010) A panel of urinary biomarkers to monitor reversibility of renal injury and a serum marker with improved potential to assess renal function. Nat Biotechnol 28:486–494CrossRefPubMedGoogle Scholar
  54. 54.
    Wacholder S, Chanock S, Garcia-Closas M, Ghormli El L, Rothman N (2004) Assessing the probability that a positive report is false: an approach for molecular epidemiology studies. J Natl Cancer Inst 96:434–442CrossRefPubMedGoogle Scholar
  55. 55.
    Yu Y, Jin H, Holder D, Ozer JS, Villarreal S, Shughrue P, Hi S, Figueroa DJ, Clouse H, Su M, Muniappa N, Troth SP, Bailey W, Seng J, Aslamkhan AG, Thudium D, Sistare FD, Gerhold DL (2010) Urinary biomarkers trefoil factor 3 and albumin enable early detection of kidney tubular injury. Nat Biotechnol 28:470–477CrossRefPubMedGoogle Scholar
  56. 56.
    Relton C, Torgerson D, O'Cathain A, Nicholl J (2010) Rethinking pragmatic randomised controlled trials: introducing the “cohort multiple randomised controlled trial” design. Br Med J 340:963–967CrossRefGoogle Scholar
  57. 57.
    Luce BR, Kramer JM, Goodman SN, Connor JT, Tunis S, Whicher D, Schwartz JS (2009) Rethinking randomized clinical trials for comparative effectiveness research: the need for transformational change. Ann Intern Med 151:206–209PubMedGoogle Scholar
  58. 58.
    Lee BS, Byun SY, Chung ML, Chang JY, Kim HY, Ai-Rhan E, Kim K-S, Pi S-Y (2010) Effect of furosemide on ductal closure and renal function in indomethacin-treated preterm infants during the early neonatal period. Neonatology 98:191–199CrossRefPubMedGoogle Scholar
  59. 59.
    Witteles RM, Kao D, Christopherson D, Matsuda K, Vagelos RH, Schreiber D, Fowler MB (2007) Impact of nesiritide on renal function in patients with acute decompensated heart failure and pre-existing renal dysfunction a randomized, double-blind, placebo-controlled clinical trial. J Am Coll Cardiol 50:1835–1840CrossRefPubMedGoogle Scholar
  60. 60.
    Gianello P, Carlier M, Jamart J, Hulhoven R, Bernheim J, Bernard A, Ketelslegers JM, Squifflet JP (1995) Effect of 1–28 alpha-h atrial natriuretic peptide on acute renal failure in cadaveric renal transplantation. Clin Transplant 9:481–489PubMedGoogle Scholar
  61. 61.
    Lewis J, Salem MM, Chertow GM, Weisberg LS, McGrew F, Marbury TC, Allgren RL (2000) Atrial natriuretic factor in oliguric acute renal failure. Anaritide Acute Renal Failure Study Group. Am J Kidney Dis 36:767–774CrossRefPubMedGoogle Scholar
  62. 62.
    Meyer M, Pfarr E, Schirmer G, Uberbacher HJ, Schöpe K, Böhm E, Fluge T, Mentz P, Scigalla P, Forssmann WG (1999) Therapeutic use of the natriuretic peptide ularitide in acute renal failure. Ren Fail 21:85–100CrossRefPubMedGoogle Scholar
  63. 63.
    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 155:1143–1149CrossRefPubMedGoogle Scholar
  64. 64.
    Sisillo E, Ceriani R, Bortone F, Juliano G, Salvi L, Veglia F, Fiorentini C, Marenzi G (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 36:81–86CrossRefPubMedGoogle Scholar
  65. 65.
    Komisarof JA, Gilkey GM, Peters DM, Koudelka CW, Meyer MM, Smith SM (2007) N-acetylcysteine for patients with prolonged hypotension as prophylaxis for acute renal failure (NEPHRON). Crit Care Med 35:435–441CrossRefPubMedGoogle Scholar
  66. 66.
    Ricci Z, Luciano R, Favia I, Garisto C, Muraca M, Morelli S, Di Chiari L, Cogo P, Picardo S (2011) High-dose fenoldopam reduces postoperative neutrophil gelatinase-associated lipocaline and cystatin C levels in pediatric cardiac surgery. Crit Care 15:R160CrossRefPubMedGoogle Scholar
  67. 67.
    Tumlin JA, Finkel K, Murray P, Samuels J, Cotsonis G, Shaw AD (2005) Fenoldopam mesylate in early acute tubular necrosis: a randomized, double-blind, placebo-controlled clinical trial. Am J Kidney Dis 46:26–34CrossRefPubMedGoogle Scholar
  68. 68.
    Myles PS, Buckland MR, Schenk NJ, Cannon GB, Langley M, Davis BB, Weeks AM (1993) Effect of “renal-dose” dopamine on renal function following cardiac surgery. Anaesth Intensive Care 21:56–61PubMedGoogle Scholar
  69. 69.
    Tang AT, El-Gamel A, Keevil B, Yonan N, Deiraniya AK (1999) The effect of “renal-dose” dopamine on renal tubular function following cardiac surgery: assessed by measuring retinol binding protein (RBP). Eur J Cardio-Thorac Surg Offic J Eur Assoc Cardio-Thorac Surg 15:717–721, discussion 721–2CrossRefGoogle Scholar
  70. 70.
    Sumeray M, Robertson C, Lapsley M, Bomanji J, Norman AG, Woolfson RG (2001) Low dose dopamine infusion reduces renal tubular injury following cardiopulmonary bypass surgery. J Nephrol 14:397–402PubMedGoogle Scholar
  71. 71.
    Swygert TH, Roberts LC, Valek TR, Brajtbord D, Brown MR, Gunning TC, Paulsen AW, Ramsay MA (1991) Effect of intraoperative low-dose dopamine on renal function in liver transplant recipients. Anesthesiology 75:571–576CrossRefPubMedGoogle Scholar
  72. 72.
    Baldwin L, Henderson A, Hickman P (1994) Effect of postoperative low-dose dopamine on renal function after elective major vascular surgery. Ann Intern Med 120:744–747PubMedGoogle Scholar
  73. 73.
    Gubern JM, Sancho JJ, Simó J, Sitges-Serra A (1988) A randomized trial on the effect of mannitol on postoperative renal function in patients with obstructive jaundice. Surgery 103:39–44PubMedGoogle Scholar
  74. 74.
    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 63:576–582CrossRefPubMedGoogle Scholar
  75. 75.
    Bennett-Guerrero E, Swaminathan M, Grigore AM, Roach GW, Aberle LG, Johnston JM, Fink MP (2009) A phase II multicenter double-blind placebo-controlled study of ethyl pyruvate in high-risk patients undergoing cardiac surgery with cardiopulmonary bypass. J Cardiothorac Vasc Anesth 23:324–329CrossRefPubMedGoogle Scholar
  76. 76.
    Krämer BK, Preuner J, Ebenburger A, Kaiser M, Bergner U, Eilles C, Kammerl MC, Riegger GAJ, Birnbaum DE (2002) Lack of renoprotective effect of theophylline during aortocoronary bypass surgery. Nephrol Dial Transplant 17:910–915CrossRefPubMedGoogle Scholar
  77. 77.
    Acker CG, Flick R, Shapiro R, Scantlebury VP, Jordan ML, Vivas C, Greenberg A, Johnson JP (2002) Thyroid hormone in the treatment of post-transplant acute tubular necrosis (ATN). Am J Transplant 2:57–61CrossRefPubMedGoogle Scholar
  78. 78.
    Voors AA, Dittrich HC, Massie BM, DeLucca P, Mansoor GA, Metra M, Gotter G, Weatherley BD, Ponikowski P, Teerlink JR, Cleland JGF, O'conner CM, Givertz MM (2011) Effects of the adenosine A1 receptor antagonist rolofylline on renal function in patients with acute heart failure and renal dysfunction: results from PROTECT (Placebo-Controlled Randomized Study of the Selective Adenosine A1 Receptor Antagonist Rolofylline for Patients Hospitalized with Acute Decompensated Heart Failure and Volume Overload to Assess Treatment Effect on Congestion and Renal Function). J Am Coll Cardiol 57:1899–1907CrossRefPubMedGoogle Scholar
  79. 79.
    Hirschberg R, Kopple J, Lipsett P, Benjamin E, Minei J, Albertson T, Mungar M, Metzler M, Zaloga G, Murray M, Lowry S, Conger J, Mckeown W, O'shea M, Baughman RP, Wook K, Haupt M, Kaiser R, Simms H, Warnock D, Summer W, Hintz R, Myers BD, Haenftling K, Capra W (1999) Multicenter clinical trial of recombinant human insulin-like growth factor I in patients with acute renal failure. Kidney Int 55:2423–2432CrossRefPubMedGoogle Scholar
  80. 80.
    Hladunewich MA, Corrigan G, Derby GC, Ramaswamy D, Kambham N, Scandling JD, Myers BD (2003) A randomized, placebo-controlled trial of IGF-1 for delayed graft function: a human model to study postischemic ARF. Kidney Int 64:593–602CrossRefPubMedGoogle Scholar
  81. 81.
    Cantarovich F, Rangoonwala B, Lorenz H, Verho M, Esnault VLM (2004) High-dose furosemide for established ARF: A prospective, randomized, double-blind, placebo-controlled, multicenter trial. Am J Kidney Dis 44:402–409PubMedGoogle Scholar
  82. 82.
    Berger M, Soguel L, Shenkin A, Revelly J-P, Pinget C, Baines M, Chiolero R (2008) Influence of early antioxidant supplements on clinical evolution and organ function in critically ill cardiac surgery, major trauma, and subarachnoid hemorrhage patients. Crit Care 12:R101CrossRefPubMedGoogle Scholar
  83. 83.
    Nouri-Majalan N, Ardakani EF, Forouzannia K, Moshtaghian H (2009) Effects of allopurinol and vitamin E on renal function in patients with cardiac coronary artery bypass grafts. Vasc Health Risk Manag 5:489–494CrossRefPubMedGoogle Scholar
  84. 84.
    Acker CG, Singh AR, Flick RP, Bernardini J, Greenberg A, Johnson JP (2000) A trial of thyroxine in acute renal failure. Kidney Int 57:293–298CrossRefPubMedGoogle Scholar
  85. 85.
    Keane WF, Hirata-Dulas CA, Bullock ML, Ney AL, Guay DR, Kalila RS, Dinarello CA, Halstenson CE, Peterson PK (1991) Adjunctive therapy with intravenous human immunoglobulin G improves survival of patients with acute renal failure. J Am Soc Nephrol 2:841–847PubMedGoogle Scholar
  86. 86.
    Prowle JR, Calzavacca P, Licari E, Ligabo EV, Echeverri JE, Haase M, Haase-Felitz A, Bagshaw SM, Devarajan P, Bellom R (2012) A pilot double-blind, randomized controlled trial of short-term atorvastatin for prevention of acute kidney injury after cardiac surgery. Nephrology 17:215–224CrossRefPubMedGoogle Scholar
  87. 87.
    Choi YS, Shim JK, Kim JC, Kang K-S, Seo YH, Ahan K-R, Kwak YL (2011) Effect of remote ischemic preconditioning on renal dysfunction after complex valvular heart surgery: a randomized controlled trial. J Thorac Cardiovasc Surg 142:148–154CrossRefPubMedGoogle Scholar
  88. 88.
    Pickering JW, Endre ZH (2009) Secondary prevention of acute kidney injury. Curr Opin Crit Care 15:488–497CrossRefPubMedGoogle Scholar
  89. 89.
    Endre ZH (2008) Acute kidney injury: definitions and new paradigms. Adv Chronic Kidney Dis 15:213–221CrossRefPubMedGoogle Scholar

Copyright information

© IPNA 2012

Authors and Affiliations

  1. 1.Christchurch Kidney Research Group, Department of MedicineUniversity of OtagoChristchurchNew Zealand
  2. 2.Department of Nephrology, Prince of Wales Clinical SchoolUniversity of New South WalesSydneyAustralia
  3. 3.Department of NephrologyPrince of Wales HospitalRandwick, SydneyAustralia

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