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Pathophysiology and management of septic acute kidney injury

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Abstract

Acute kidney injury (AKI) is a commonly encountered complication in critically ill children and portends a worse prognosis. Sepsis-induced AKI (SAKI) is a leading contributor to AKI in children and significantly modifies the risk for less favorable outcome. It has increasingly become clear that SAKI represents a unique and distinct cause of AKI. Studies focused on renal hemodynamics, bioenergetics, and immune-mediated injury have provided further insights into the pathobiology of SAKI; however, many of the nuanced mechanisms remain incompletely understood. Although there have been numerous strategies evaluated for the prevention and management of SAKI, no specific intervention has proven unequivocally efficacious. Currently, the mainstays for managing SAKI focus on alleviating ongoing kidney damage by optimizing systemic and kidney hemodynamic support, avoiding nephrotoxins, and mitigating the anticipated complications of kidney failure. The timely referral for renal support to manage azotemia, metabolic derangements, and fluid accumulation remains critical for this population. The extracorporeal removal of inflammatory mediators has shown some potential benefit in limiting systemic and kidney immune-mediated injury; however, the precise role of these technologies in the management of SAKI has yet to be defined.

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References

  1. Bunchman TE (2008) Treatment of acute kidney injury in children: from conservative management to renal replacement therapy. Nat Clin Pract Nephrol 4:510–514

    Article  PubMed  CAS  Google Scholar 

  2. Bailey D, Phan V, Litalien C, Ducruet T, Merouani A, Lacroix J, Gauvin F (2007) Risk factors of acute renal failure in critically ill children: A prospective descriptive epidemiological study. Pediatr Crit Care Med 8:29–35

    Article  PubMed  Google Scholar 

  3. Schneider J, Khemani R, Grushkin C, Bart R (2010) Serum creatinine as stratified in the RIFLE score for acute kidney injury is associated with mortality and length of stay for children in the pediatric intensive care unit. Crit Care Med 38:933–939

    Article  PubMed  CAS  Google Scholar 

  4. Akcan-Arikan A, Zappitelli M, Loftis LL, Washburn KK, Jefferson LS, Goldstein SL (2007) Modified RIFLE criteria in critically ill children with acute kidney injury. Kidney Int 71:1028–1035

    Article  PubMed  CAS  Google Scholar 

  5. Wheeler DS, Devarajan P, Ma Q, Harmon K, Monaco M, Cvijanovich N, Wong HR (2008) Serum neutrophil gelatinase-associated lipocalin (NGAL) as a marker of acute kidney injury in critically ill children with septic shock. Crit Care Med 36:1297–1303

    Article  PubMed  CAS  Google Scholar 

  6. Zappitelli M, Washburn KK, Arikan AA, Loftis L, Ma Q, Devarajan P, Parikh CR, Goldstein SL (2007) Urine neutrophil gelatinase-associated lipocalin is an early marker of acute kidney injury in critically ill children: a prospective cohort study. Crit Care 11:R84

    Article  PubMed  Google Scholar 

  7. Zappitelli M, Moffett BS, Hyder A, Goldstein SL (2011) Acute kidney injury in non-critically ill children treated with aminoglycoside antibiotics in a tertiary healthcare centre: a retrospective cohort study. Nephrol Dial Transplant 26:144–150

    Article  PubMed  Google Scholar 

  8. Mammen C, Al Abbas A, Skippen P, Nadel H, Levine D, Collet JP, Matsell DG (2012) Long-term risk of CKD in children surviving episodes of acute kidney injury in the intensive care unit: a prospective cohort study. Am J Kidney Dis 59:523–530

    Article  PubMed  Google Scholar 

  9. Shaheen IS, Watson AR, Harvey B (2006) Acute renal failure in children: etiology, treatment and outcome. Saudi J Kidney Dis Transpl 17:153–158

    PubMed  Google Scholar 

  10. Watson RS, Carcillo JA, Linde-Zwirble WT, Clermont G, Lidicker J, Angus DC (2003) The epidemiology of severe sepsis in children in the United States. Am J Respir Crit Care Med 167:695–701

    Article  PubMed  Google Scholar 

  11. Watson RS, Carcillo JA (2005) Scope and epidemiology of pediatric sepsis. Pediatr Crit Care Med 6:S3–5

    Article  PubMed  Google Scholar 

  12. Fiser RT, West NK, Bush AJ, Sillos EM, Schmidt JE, Tamburro RF (2005) Outcome of severe sepsis in pediatric oncology patients. Outcome of severe sepsis in pediatric oncology patients. Pediatr Critl Care Med 6:531–536

    Article  Google Scholar 

  13. Martin GS, Mannino DM, Eaton S, Moss M (2003) The epidemiology of sepsis in the United States from 1979 through 2000. N Engl J Med 348:1546–1554

    Article  PubMed  Google Scholar 

  14. Bagshaw SM, George C, Bellomo R (2008) Early acute kidney injury and sepsis: a multicentre evaluation. Crit Care 12:R47

    Article  PubMed  Google Scholar 

  15. Loza R, Estremadoyro L, Loza C, Cieza J (2006) Factors associated with mortality in acute renal failure (ARF) in children. Pediatr Nephrol 21:106–109

    Article  PubMed  Google Scholar 

  16. Vachvanichsanong P, Dissaneewate P, Lim A, McNeil E (2006) Childhood acute renal failure: 22-year experience in a university hospital in southern Thailand. Pediatrics 118:e786–791

    Article  PubMed  Google Scholar 

  17. Duzova A, Bakkaloglu A, Kalyoncu M, Poyrazoglu H, Delibas A, Ozkaya O, Peru H, Alpay H, Soylemezoglu O, Gur-Guven A, Bak M, Bircan Z, Cengiz N, Akil I, Ozcakar B, Uncu N, Karabay-Bayazit A, Sonmez F (2010) Etiology and outcome of acute kidney injury in children. Pediatr Nephrol 25:1453–1461

    Article  PubMed  Google Scholar 

  18. Alkandari O, Eddington KA, Hyder A, Gauvin F, Ducruet T, Gottesman R, Phan V, Zappitelli M (2011) Acute kidney injury is an independent risk factor for pediatric intensive care unit mortality, longer length of stay and prolonged mechanical ventilation in critically ill children: a two-center retrospective cohort study. Crit Care 15:R146

    Article  PubMed  Google Scholar 

  19. Mehta P, Sinha A, Sami A, Hari P, Kalaivani M, Gulati A, Kabra M, Kabra SK, Lodha R, Bagga A (2012) Incidence of acute kidney injury in hospitalized children. Indian Pediatr 49:537–542

    Article  PubMed  Google Scholar 

  20. Palmieri T, Lavrentieva A, Greenhalgh D (2009) An assessment of acute kidney injury with modified RIFLE criteria in pediatric patients with severe burns. Intensive Care Med 35:2125–2129

    Article  PubMed  Google Scholar 

  21. Vachvanichsanong P, McNeil E, Dissaneevate S, Dissaneewate P, Chanvitan P, Janjindamai W (2012) Neonatal acute kidney injury in a tertiary center in a developing country. Nephrol Dial Transplant 27:973–977

    Article  PubMed  Google Scholar 

  22. Pundziene B, Dobiliene D, Rudaitis S (2010) Acute kidney injury in pediatric patients: experience of a single center during an 11-year period. Medicina (Kaunas) 46:511–515

    Google Scholar 

  23. Mehta RL, Bouchard J, Soroko SB, Ikizler TA, Paganini EP, Chertow GM, Himmelfarb J (2011) Sepsis as a cause and consequence of acute kidney injury: Program to Improve Care in Acute Renal Disease. Intensive Care Med 37:241–248

    Article  PubMed  Google Scholar 

  24. Bagshaw SM, Uchino S, Bellomo R, Morimatsu H, Morgera S, Schetz M, Tan I, Bouman C, Macedo E, Gibney N, Tolwani A, Oudemans-van Straaten HM, Ronco C, Kellum JA (2007) Septic acute kidney injury in critically ill patients: clinical characteristics and outcomes. Clin J Am Soc Nephrol 2:431–439

    Article  PubMed  Google Scholar 

  25. Chang JW, Tsai HL, Wang HH, Yang LY (2008) Outcome and risk factors for mortality in children with acute renal failure. Clin Nephrol 70:485–489

    Article  PubMed  Google Scholar 

  26. Plotz FB, Hulst HE, Twisk JW, Bokenkamp A, Markhorst DG, van Wijk JA (2005) Effect of acute renal failure on outcome in children with severe septic shock. Pediatr Nephrol 20:1177–1181

    Article  PubMed  Google Scholar 

  27. Langenberg C, Bagshaw SM, May CN, Bellomo R (2008) The histopathology of septic acute kidney injury: a systematic review. Crit Care 12:R38

    Article  PubMed  Google Scholar 

  28. Bagshaw SM, Langenberg C, Bellomo R (2006) Urinary biochemistry and microscopy in septic acute renal failure: a systematic review. Am J Kidney Dis 48:695–705

    Article  PubMed  CAS  Google Scholar 

  29. Bagshaw SM, Bennett M, Devarajan P, Bellomo R (2012) Urine biochemistry in septic and non-septic acute kidney injury: a prospective observational study. J Crit Care. doi:10.1016/j.jcrc.2012.10.007

  30. Bagshaw SM, Haase M, Haase-Fielitz A, Bennett M, Devarajan P, Bellomo R (2012) A prospective evaluation of urine microscopy in septic and non-septic acute kidney injury. Nephrol Dial Transplant 27:582–588

    Article  PubMed  CAS  Google Scholar 

  31. Wen X, Peng Z, Li Y, Wang H, Bishop JV, Chedwick LR, Singbartl K, Kellum JA (2012) One dose of cyclosporine A is protective at initiation of folic acid-induced acute kidney injury in mice. Nephrol Dial Transplant 27:3100–3109

    Article  PubMed  CAS  Google Scholar 

  32. Langenberg C, Bellomo R, May C, Wan L, Egi M, Morgera S (2005) Renal blood flow in sepsis. Crit Care 9:R363–374

    Article  PubMed  Google Scholar 

  33. Langenberg C, Wan L, Egi M, May CN, Bellomo R (2006) Renal blood flow in experimental septic acute renal failure. Kidney Int 69:1996–2002

    Article  PubMed  CAS  Google Scholar 

  34. Langenberg C, Wan L, Bagshaw SM, Egi M, May CN, Bellomo R (2006) Urinary biochemistry in experimental septic acute renal failure. Nephrol Dial Transplant 104:1–11

    Google Scholar 

  35. May CN, Ishikawa K, Wan L, Williams J, Wellard RM, Pell GS, Jackson GD, Bellomo R (2012) Renal bioenergetics during early gram-negative mammalian sepsis and angiotensin II infusion. Intensive Care Med 38:886–893

    Article  PubMed  CAS  Google Scholar 

  36. Wan L, Langenberg C, Bellomo R, May CN (2009) Angiotensin II in experimental hyperdynamic sepsis. Crit Care 13:R190

    Article  PubMed  Google Scholar 

  37. Top AP, Tasker RC, Ince C (2011) The microcirculation of the critically ill pediatric patient. Crit Care 15:213

    Article  PubMed  Google Scholar 

  38. Weiss SL, Yu M, Jennings L, Haymond S, Zhang G, Wainwright MS (2012) Pilot study of the association of the DDAH2–449 G polymorphism with asymmetric dimethylarginine and hemodynamic shock in pediatric sepsis. PLoS One 7:e33355

    Article  PubMed  CAS  Google Scholar 

  39. Seely KA, Holthoff JH, Burns ST, Wang Z, Thakali KM, Gokden N, Rhee SW, Mayeux PR (2011) Hemodynamic changes in the kidney in a pediatric rat model of sepsis-induced acute kidney injury. Am J Physiol Renal Physiol 301:F209–217

    Article  PubMed  CAS  Google Scholar 

  40. Brenner M, Schaer GL, Mallory DL, Suffredini AF, Parrillo JE (1990) Detection of renal blood flow abnormalities in septic and critically ill patients using a newly designed indwelling thermodilution renal vein catheter. Chest 98:170–179

    Article  PubMed  CAS  Google Scholar 

  41. Prowle JR, Molan MP, Hornsey E, Bellomo R (2012) Measurement of renal blood flow by phase-contrast magnetic resonance imaging during septic acute kidney injury: a pilot investigation. Crit Care Med 40:1768–1776

    Article  PubMed  Google Scholar 

  42. Di Giantomasso D, Morimatsu H, May CN, Bellomo R (2003) Intrarenal blood flow distribution in hyperdynamic septic shock: Effect of norepinephrine. Crit Care Med 31:2509–2513

    Article  PubMed  Google Scholar 

  43. May C, Wan L, Williams J, Wellard MR, Pell G, Jackson G, Bellomo R (2005) A technique for the measurement of renal ATP in a large animal model of septic shock. Int J Artif Organs 28:16–21

    PubMed  CAS  Google Scholar 

  44. Gustot T (2011) Multiple organ failure in sepsis: prognosis and role of systemic inflammatory response. Curr Opin Crit Care 17:153–159

    Article  PubMed  Google Scholar 

  45. Cunningham PN, Dyanov HM, Park P, Wang J, Newell KA, Quigg RJ (2002) Acute renal failure in endotoxemia is caused by TNF acting directly on TNF receptor-1 in kidney. J Immunol 168:5817–5823

    PubMed  CAS  Google Scholar 

  46. Cunningham PN, Wang Y, Guo R, He G, Quigg RJ (2004) Role of Toll-like receptor 4 in endotoxin-induced acute renal failure. J Immunol 172:2629–2635

    PubMed  CAS  Google Scholar 

  47. Guo R, Wang Y, Minto AW, Quigg RJ, Cunningham PN (2004) Acute renal failure in endotoxemia is dependent on caspase activation. J Am Soc Nehrol 15:3093–3102

    Article  Google Scholar 

  48. Kockara A, Kayatas M (2012) Renal cell apoptosis and new treatment options in sepsis-induced acute kidney injury. Ren Fail. doi:10.3109/0886022X.2012.744040

  49. Lee SY, Lee YS, Choi HM, Ko YS, Lee HY, Jo SK, Cho WY, Kim HK (2012) Distinct pathophysiologic mechanisms of septic acute kidney injury: role of immune suppression and renal tubular cell apoptosis in murine model of septic acute kidney injury. Crit Care Med 40:2997–3006

    Article  PubMed  CAS  Google Scholar 

  50. Lerolle N, Nochy D, Guerot E, Bruneval P, Fagon JY, Diehl JL, Hill G (2010) Histopathology of septic shock induced acute kidney injury: apoptosis and leukocytic infiltration. Intensive Care Med 36:471–478

    Article  PubMed  Google Scholar 

  51. Rana A, Sathyanarayana P, Lieberthal W (2001) Role of apoptosis of renal tubular cells in acute renal failure: therapeutic implications. Apoptosis 6:83–102

    Article  PubMed  CAS  Google Scholar 

  52. Schor N (2002) Acute renal failure and the sepsis syndrome. Kidney Int 61:764–776

    Article  PubMed  Google Scholar 

  53. Wan L, Bagshaw SM, Langenberg C, Saotome T, May C, Bellomo R (2008) Pathophysiology of septic acute kidney injury: what do we really know? Crit Care Med 36:S198–203

    Article  PubMed  Google Scholar 

  54. Knotek M, Rogachev B, Wang W, Ecder T, Melnikov V, Gengaro PE, Esson M, Edelstein CL, Dinarello CA, Schrier RW (2001) Endotoxemic renal failure in mice: Role of tumor necrosis factor independent of inducible nitric oxide synthase. Kidney Int 59:2243–2249

    PubMed  CAS  Google Scholar 

  55. Benes J, Chvojka J, Sykora R, Radej J, Krouzecky A, Novak I, Matejovic M (2011) Searching for mechanisms that matter in early septic acute kidney injury: an experimental study. Crit Care 15:R256

    Article  PubMed  Google Scholar 

  56. Khan RZ, Badr KF (1999) Endotoxin and renal function: perspectives to the understanding of septic acute renal failure and toxic shock. Nephrol Dial Transplant 14:814–818

    Article  PubMed  CAS  Google Scholar 

  57. Payen D, Lukaszewicz AC, Legrand M, Gayat E, Faivre V, Megarbane B, Azoulay E, Fieux F, Charron D, Loiseau P, Busson M (2012) A multicentre study of acute kidney injury in severe sepsis and septic shock: association with inflammatory phenotype and HLA genotype. PLoS One 7:e35838

    Article  PubMed  CAS  Google Scholar 

  58. Brierley J, Carcillo JA, Choong K, Cornell T, Decaen A, Deymann A, Doctor A, Davis A, Duff J, Dugas MA, Duncan A, Evans B, Feldman J, Felmet K, Fisher G, Frankel L, Jeffries H, Greenwald B, Gutierrez J, Hall M, Han YY, Hanson J, Hazelzet J, Hernan L, Kiff J, Kissoon N, Kon A, Irazuzta J, Lin J, Lorts A, Mariscalco M, Mehta R, Nadel S, Nguyen T, Nicholson C, Peters M, Okhuysen-Cawley R, Poulton T, Relves M, Rodriguez A, Rozenfeld R, Schnitzler E, Shanley T, Kache S, Skippen P, Torres A, von Dessauer B, Weingarten J, Yeh T, Zaritsky A, Stojadinovic B, Zimmerman J, Zuckerberg A (2009) Clinical practice parameters for hemodynamic support of pediatric and neonatal septic shock: 2007 update from the American College of Critical Care Medicine. Crit Care Med 37:666–688

    Article  PubMed  Google Scholar 

  59. de Oliveira CF, de Oliveira DS, Gottschald AF, Moura JD, Costa GA, Ventura AC, Fernandes JC, Vaz FA, Carcillo JA, Rivers EP, Troster EJ (2008) ACCM/PALS haemodynamic support guidelines for paediatric septic shock: an outcomes comparison with and without monitoring central venous oxygen saturation. Intensive Care Med 34:1065–1075

    Article  PubMed  Google Scholar 

  60. Shaw AD, Bagshaw SM, Goldstein SL, Scherer LA, Duan M, Schermer CR, Kellum JA (2012) Major complications, mortality, and resource utilization after open abdominal surgery: 0.9 % saline compared to Plasma-Lyte. Ann Surg 255:821–829

    Article  PubMed  Google Scholar 

  61. Yunos NM, Bellomo R, Hegarty C, Story D, Ho L, Bailey M (2012) Association between a chloride-liberal vs chloride-restrictive intravenous fluid administration strategy and kidney injury in critically ill adults. JAMA 308:1566–1572

    Article  PubMed  CAS  Google Scholar 

  62. Brunkhorst FM, Engel C, Bloos F, Meier-Hellmann A, Ragaller M, Weiler N, Moerer O, Gruendling M, Oppert M, Grond S, Olthoff D, Jaschinski U, John S, Rossaint R, Welte T, Schaefer M, Kern P, Kuhnt E, Kiehntopf M, Hartog C, Natanson C, Loeffler M, Reinhart K (2008) Intensive insulin therapy and pentastarch resuscitation in severe sepsis. N Engl J Med 358:125–139

    Article  PubMed  CAS  Google Scholar 

  63. Myburgh JA, Finfer S, Bellomo R, Billot L, Cass A, Gattas D, Glass P, Lipman J, Liu B, McArthur C, McGuinness S, Rajbhandari D, Taylor CB, Webb SA (2012) Hydroxyethyl starch or saline for fluid resuscitation in intensive care. N Engl J Med 367:1901–1911

    Article  PubMed  CAS  Google Scholar 

  64. Perner A, Haase N, Guttormsen AB, Tenhunen J, Klemenzson G, Aneman A, Madsen KR, Moller MH, Elkjaer JM, Poulsen LM, Bendtsen A, Winding R, Steensen M, Berezowicz P, Soe-Jensen P, Bestle M, Strand K, Wiis J, White JO, Thornberg KJ, Quist L, Nielsen J, Andersen LH, Holst LB, Thormar K, Kjaeldgaard AL, Fabritius ML, Mondrup F, Pott FC, Moller TP, Winkel P, Wetterslev J (2012) Hydroxyethyl starch 130/0.42 versus Ringer’s acetate in severe sepsis. N Engl J Med 367:124–134

    Article  PubMed  CAS  Google Scholar 

  65. Sutherland SM, Zappitelli M, Alexander SR, Chua AN, Brophy PD, Bunchman TE, Hackbarth R, Somers MJ, Baum M, Symons JM, Flores FX, Benfield M, Askenazi D, Chand D, Fortenberry JD, Mahan JD, McBryde K, Blowey D, Goldstein SL (2010) Fluid overload and mortality in children receiving continuous renal replacement therapy: the prospective pediatric continuous renal replacement therapy registry. Am J Kidney Dis 55:316–325

    Article  PubMed  Google Scholar 

  66. Finfer S, Liu B, Taylor C, Bellomo R, Billot L, Cook D, Du B, McArthur C, Myburgh J (2010) Resuscitation fluid use in critically ill adults: an international cross-sectional study in 391 intensive care units. Crit Care 14:R185

    Article  PubMed  Google Scholar 

  67. Akech S, Ledermann H, Maitland K (2010) Choice of fluids for resuscitation in children with severe infection and shock: systematic review. Br Med J 341:c4416

    Article  Google Scholar 

  68. Upadhyay M, Singhi S, Murlidharan J, Kaur N, Majumdar S (2005) Randomized evaluation of fluid resuscitation with crystalloid (saline) and colloid (polymer from degraded gelatin in saline) in pediatric septic shock. Indian Pediatr 42:223–231

    PubMed  Google Scholar 

  69. Reinhart K, Perner A, Sprung CL, Jaeschke R, Schortgen F, Johan Groeneveld AB, Beale R, Hartog CS (2012) Consensus statement of the ESICM task force on colloid volume therapy in critically ill patients. Intensive Care Med 38:368–383

    Article  PubMed  CAS  Google Scholar 

  70. Chua HR, Venkatesh B, Stachowski E, Schneider AG, Perkins K, Ladanyi S, Kruger P, Bellomo R (2012) Plasma-Lyte 148 vs 0.9 % saline for fluid resuscitation in diabetic ketoacidosis. J Crit Care 27:138–145

    Article  PubMed  CAS  Google Scholar 

  71. Yunos NM, Kim IB, Bellomo R, Bailey M, Ho L, Story D, Gutteridge GA, Hart GK (2011) The biochemical effects of restricting chloride-rich fluids in intensive care. Crit Care Med 39:2419–2424

    Article  PubMed  CAS  Google Scholar 

  72. Myburgh J, Cooper DJ, Finfer S, Bellomo R, Norton R, Bishop N, Kai Lo S, Vallance S (2007) Saline or albumin for fluid resuscitation in patients with traumatic brain injury. N Engl J Med 357:874–884

    Article  PubMed  CAS  Google Scholar 

  73. Bouchard J, Soroko SB, Chertow GM, Himmelfarb J, Ikizler TA, Paganini EP, Mehta RL (2009) Fluid accumulation, survival and recovery of kidney function in critically ill patients with acute kidney injury. Kidney Int 76:422–427

    Article  PubMed  Google Scholar 

  74. Grams ME, Estrella MM, Coresh J, Brower RG, Liu KD (2011) Fluid balance, diuretic use, and mortality in acute kidney injury. Clin J Am Soc Nephrol 6:966–973

    Article  PubMed  Google Scholar 

  75. Arikan AA, Zappitelli M, Goldstein SL, Naipaul A, Jefferson LS, Loftis LL (2012) Fluid overload is associated with impaired oxygenation and morbidity in critically ill children. Pediatr Crit Care Med 13:253–258

    Article  PubMed  Google Scholar 

  76. Goldstein SL, Somers MJ, Baum MA, Symons JM, Brophy PD, Blowey D, Bunchman TE, Baker C, Mottes T, McAfee N, Barnett J, Morrison G, Rogers K, Fortenberry JD (2005) Pediatric patients with multi-organ dysfunction syndrome receiving continuous renal replacement therapy. Kidney Int 67:653–658

    Article  PubMed  Google Scholar 

  77. Maitland K, Kiguli S, Opoka RO, Engoru C, Olupot-Olupot P, Akech SO, Nyeko R, Mtove G, Reyburn H, Lang T, Brent B, Evans JA, Tibenderana JK, Crawley J, Russell EC, Levin M, Babiker AG, Gibb DM (2011) Mortality after fluid bolus in African children with severe infection. N Engl J Med 364:2483–2495

    Article  PubMed  CAS  Google Scholar 

  78. Mehta RL, Pascual MT, Soroko S, Chertow GM (2002) Diuretics, mortality, and nonrecovery of renal function in acute renal failure. JAMA 288:2547–2553

    Article  PubMed  CAS  Google Scholar 

  79. Bagshaw SM, Gibney RT, McAlister FA, Bellomo R (2010) The SPARK Study: a phase II randomized blinded controlled trial of the effect of furosemide in critically ill patients with early acute kidney injury. Trials 11:50

    Article  PubMed  Google Scholar 

  80. De Backer D, Aldecoa C, Njimi H, Vincent JL (2012) Dopamine versus norepinephrine in the treatment of septic shock: a meta-analysis. Crit Care Med 40:725–730

    Article  PubMed  Google Scholar 

  81. Bellomo R, Chapman M, Finfer S, Hickling K, Myburgh J (2000) Low-dose dopamine in patients with early renal dysfunction: a placebo-controlled randomised trial. Australian and New Zealand Intensive Care Society (ANZICS) Clinical Trials Group. Lancet 356:2139–2143

    Article  PubMed  CAS  Google Scholar 

  82. Morelli A, Ricci Z, Bellomo R, Ronco C, Rocco M, Conti G, De Gaetano A, Picchini U, Orecchioni 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 33:2451–2456

    Article  PubMed  CAS  Google Scholar 

  83. Gordon AC, Russell JA, Walley KR, Singer J, Ayers D, Storms MM, Holmes CL, Hebert PC, Cooper DJ, Mehta S, Granton JT, Cook DJ, Presneill JJ (2010) The effects of vasopressin on acute kidney injury in septic shock. Intensive Care Med 36:83–91

    Article  PubMed  CAS  Google Scholar 

  84. Bellomo R, Ronco C, Kellum JA, Mehta RL, Palevsky P (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:R204–212

    Article  PubMed  Google Scholar 

  85. Edwards RM, Trizna W, Kinter LB (1989) Renal microvascular effects of vasopressin and vasopressin antagonists. Am J Physiol 256:F274–278

    PubMed  CAS  Google Scholar 

  86. Heemskerk S, Masereeuw R, Moesker O, Bouw MP, van der Hoeven JG, Peters WH, Russel FG, Pickkers P (2009) Alkaline phosphatase treatment improves renal function in severe sepsis or septic shock patients. Crit Care Med 37(417–423):e411

    Google Scholar 

  87. Pickkers P, Heemskerk S, Schouten J, Laterre PF, Vincent JL, Beishuizen A, Jorens PG, Spapen H, Bulitta M, Peters WH, van der Hoeven JG (2012) Alkaline phosphatase for treatment of sepsis-induced acute kidney injury: a prospective randomized double-blind placebo-controlled trial. Crit Care 16:R14

    Article  PubMed  Google Scholar 

  88. Bagshaw SM, Lapinsky S, Dial S, Arabi Y, Dodek P, Wood G, Ellis P (2008) Acute kidney injury in septic shock: clinical outcomes and impact of duration of hypotension prior to initiation of antimicrobial therapy. Intensive Care Med 35(5):871–881

    Article  PubMed  Google Scholar 

  89. Brar SS, Hiremath S, Dangas G, Mehran R, Brar SK, Leon MB (2009) Sodium bicarbonate for the prevention of contrast induced-acute kidney injury: a systematic review and meta-analysis. Clin J Am Soc Nephrol 4:1584–1592

    Article  PubMed  CAS  Google Scholar 

  90. Heinrich MC, Haberle L, Muller V, Bautz W, Uder M (2009) Nephrotoxicity of iso-osmolar iodixanol compared with nonionic low-osmolar contrast media: meta-analysis of randomized controlled trials. Radiology 250:68–86

    Article  PubMed  Google Scholar 

  91. Song K, Jiang S, Shi Y, Shen H, Shi X, Jing D (2010) Renal replacement therapy for prevention of contrast-induced acute kidney injury: a meta-analysis of randomized controlled trials. Am J Nephrol 32:497–504

    Article  PubMed  Google Scholar 

  92. Kidney Disease: Improving Global Outcomes (KDIGO) (2012) KDIGO clinical practice guidelines for acute kidney injury. Kidney Int 2:1–138

    Article  Google Scholar 

  93. Karvellas CJ, Farhat MR, Sajjad I, Mogensen SS, Leung AA, Wald R, Bagshaw SM (2011) A comparison of early versus late initiation of renal replacement therapy in critically ill patients with acute kidney injury: a systematic review and meta-analysis. Crit Care 15:R72

    Article  PubMed  Google Scholar 

  94. Bagshaw SM, Berthiaume LR, Delaney A, Bellomo R (2008) Continuous versus intermittent renal replacement therapy for critically ill patients with acute kidney injury: a meta-analysis. Crit Care Med 36:610–617

    Article  PubMed  Google Scholar 

  95. Bonilla-Felix M (2009) Peritoneal dialysis in the pediatric intensive care unit setting. Perit Dial Int 29[Suppl 2]:S183–185

    PubMed  Google Scholar 

  96. Flynn JT, Kershaw DB, Smoyer WE, Brophy PD, McBryde KD, Bunchman TE (2001) Peritoneal dialysis for management of pediatric acute renal failure. Perit Dial Int 21:390–394

    PubMed  CAS  Google Scholar 

  97. Ronco C, Bellomo R, Homel P, Brendolan A, Dan M, Piccinni P, La Greca G (2000) Effects of different doses in continuous veno-venous haemofiltration on outcomes of acute renal failure: a prospective randomised trial. Lancet 356:26–30

    Article  PubMed  CAS  Google Scholar 

  98. Bellomo R, Cass A, Cole L, Finfer S, Gallagher M, Lo S, McArthur C, McGuinness S, Myburgh J, Norton R, Scheinkestel C, Su S (2009) Intensity of continuous renal-replacement therapy in critically ill patients. New Engl J Med 361:1627–1638

    Article  PubMed  Google Scholar 

  99. Palevsky PM, Zhang JH, O’Connor TZ, Chertow GM, Crowley ST, Choudhury D, Finkel K, Kellum JA, Paganini E, Schein RM, Smith MW, Swanson KM, Thompson BT, Vijayan A, Watnick S, Star RA, Peduzzi P (2008) Intensity of renal support in critically ill patients with acute kidney injury. New Engl J Med 359:7–20

    Article  PubMed  CAS  Google Scholar 

  100. Faubel S, Chawla LS, Chertow GM, Goldstein SL, Jaber BL, Liu KD (2012) Ongoing clinical trials in AKI. Clin J Am Soc Nephrol 7:861–873

    Article  PubMed  Google Scholar 

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Acknowledgments

S.M. Bagshaw is supported by a Canada Research Chair in Critical Care Nephrology and Clinical Investigator Award from Alberta Innovates–Health Solutions.

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Romanovsky, A., Morgan, C. & Bagshaw, S.M. Pathophysiology and management of septic acute kidney injury. Pediatr Nephrol 29, 1–12 (2014). https://doi.org/10.1007/s00467-013-2427-6

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  • DOI: https://doi.org/10.1007/s00467-013-2427-6

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