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VOLUME 14 , ISSUE 1 ( January, 2010 ) > List of Articles


Sepsis-induced acute kidney injury

Arghya Majumdar

Keywords : Sepsis, acute kidney injury, AKI, acute renal failure, extracorporeal purification of blood

Citation Information : Majumdar A. Sepsis-induced acute kidney injury. Indian J Crit Care Med 2010; 14 (1):14-21.

DOI: 10.4103/0972-5229.63031

License: CC BY-ND 3.0

Published Online: 01-10-2012

Copyright Statement:  Copyright © 2010; The Author(s).


Acute kidney injury (AKI) is a common sequel of sepsis in the intensive care unit. It is being suggested that sepsis-induced AKI may have a distinct pathophysiology and identity. Availability of biomarkers now enable us to detect AKI as early as four hours after it′s inception and may even help us to delineate sepsis-induced AKI. Protective strategies such as preferential use of vasopressin or prevention of intra-abdominal hypertension may help, in addition to the other global management strategies of sepsis. Pharmacologic interventions have had limited success, may be due to their delayed usage. Newer developments in extracorporeal blood purification techniques may proffer effects beyond simple replacement of renal function, such as metabolic functions of the kidney or modulation of the sepsis cascade.

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  1. Rangel-Frausto MS, Pittet D, Costigan M, Hwang T, Davis CS, Wenzel RP. The natural history of the Systemic Inflammatory Response Syndrome (SIRS): A prospective study. JAMA 1995;273:117-23.
  2. Bagshaw SM, Uchino S, Bellomo R, Morimatsu H, Morgera S, Schetz M, et al. Septic acute kidney injury in critically ill patients: Clinical characteristics and outcomes. Clin J Am Soc Nephrol 2007;2:431-9.
  3. Wan L, Bagshaw SM, Langenberg C, Saotome T, May C, Bellomo R. Pathophysiology of septic acute kidney injury: What do we really know? Crit. Care Med 2008;36:S198-203.
  4. Bellomo R, Ronco C, Kellum JA, Mehta RL, Palevsky P; Acute Dialysis Quality Initiative workgroup. 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 2004;8:R204-12.
  5. Mehta RL, Kellum JA, Shah SV, Molitoris BA, Ronco C, Warnock DG, et al. Acute kidney injury network: Report of an initiative to improve outcomes in acute kidney injury. Crit Care 2007;11:R31.
  6. Mishra J, Dent C, Tarabishi R, Mitsnefes MM, Ma Q, Kelly C, et al. Neutrophil gelatinase-associated lipocalin (NGAL) as a biomarker for acute renal injury following cardiac surgery. Lancet 2005;365:1231-8.
  7. Herget-Rosenthal S, Marggraf G, Hόsing J, Gφring F, Pietruck F, Janssen O, et al. Early detection of acute renal failure by serum cystatin C. Kidney Int 2004;66:1115-22.
  8. Wagener G, Jan M, Kim M, Mori K, Barasch JM, Sladen RN, et al. Association between increases in urinary neutrophil gelatinase-associated lipocalin and acute renal dysfunction after adult cardiac surgery. Anesthesiology 2006;105:485-91.
  9. Parikh CR, Jani A, Melnikov VY, Faubel S, Edelstein CL. Urinary interleukin-18 is a marker of human acute tubular necrosis. Am J Kidney Dis 2004;43:405-14.
  10. Liangos O, Han WK, Wald R. Urinary kidney injury molecule-1 level is an early and sensitive marker of acute kidney injury following cardiopulmonary bypass. J Am Soc Nephrol 2006;17:403A.
  11. Bagshaw SM, Bennet M, Haase M, Haase-Fielitz A, Egi M, Morimatsu H, et al. Plasma and urine neutrophil gelatinase- associated lipocalin in septic versus non- septic acute kidney injury in critical illness. Intensive Care Med 2010;36:452-61.
  12. Pelte CH, Chawla LS. Novel therapeutic targets for prevention and therapy of sepsis associated acute kidney injury. Curr Drug Targets 2009;10:1205-11.
  13. Wan L, Bagshaw SM, Langenberg C, Saotome T, May C, Bellomo R. Pathophysiology of septic acute kidney injury: What do we really know? Crit Care Med 2008;36:S198-203.
  14. Lopes JA, Jorge S, Resina C, Santos C, Pereira A, Neves J, et al. Acute renal failure in patients with sepsis. Crit Care 2007;11:411.
  15. Opal SM, Scannon PJ, Vincent JL, White M, Carroll SF, Palardy JE, et al. Relationship between plasma levels of lipopolysaccharide (LPS) and LPS-binding protein in patients with severe sepsis and septic shock. J Infect Dis 1999;180:1584-9.
  16. Marshall JC. Lipopolysaccharide: An endotoxin or an exogenous hormone? Clin Infect Dis 2005;41:S470-80.
  17. Braude AI, Carey FJ, Zalesky M. Studies with radioactive endotoxin: II: Correlation of physiologic effects with distribution of radioactivity in rabbits injected with radioactive sodium chromate. J Clin Invest 1955;34:858-66.
  18. de Haas CJ, van Leeuwen HJ, Verhoef J, van Kessel KP, van Strijp JA. Analysis of lipopolysaccharide (LPS)-binding characteristics of serum components using gel filtration of FITC-labeled LPS. J Immunol Methods 2000;242:79-89.
  19. Triantafilou M, Triantafilou, K. Lipopolysaccharide recognition: CD14, TLRs and the LPS-activation cluster. Trends Immunol 2002;23:301-4.
  20. Chowdhury P, Sacks SH, Sheerin NS. Toll-like receptors TLR2 and TLR4 initiate the innate immune response of the renal tubular epithelium to bacterial products. Clin Exp Immunol 2006;145:346-56.
  21. Lopez-Bojorquez LN, Dehesa AZ, Reyes-Teran G. Molecular mechanisms involved in the pathogenesis of septic shock. Arch Med Res.2004;35:465-79.
  22. Dear JW, Yasuda H, Hu X, Hieny S, Yuen PS, Hewitt SM, et al. Sepsis-induced organ failure is mediated by different pathways in the kidney and liver: Acute renal failure is dependent on MyD88 but not renal cell apoptosis. Kidney Int 2006;69:832-6.
  23. Cohen J. The immunopathogenesis of sepsis. Nature 2002;420:885-91.
  24. Al-Lamki RS, Wang J, Skepper JN, Thiru S, Pober JS, Bradley JR. Expression of tumor necrosis factor receptors in normal kidney and rejecting renal transplants. Lab Invest 2001;81:1503-15.
  25. Thiemermann C. Nitric oxide and septic shock. Gen Pharmacol 1997;29:159-66.
  26. Schrier RW, Wang W. Acute renal failure and sepsis. N Engl J Med 2004;351:159-69.
  27. Knotek M, Rogachev B, Wang W, Ecder T, Melnikov V, Gengaro PE, et al. Endotoxemic renal failure in mice: Role of tumor necrosis factor independent of inducible nitric oxide synthase. Kidney Int 2001;59:2243-9.
  28. Millar CG, Thiemermann C. Intrarenal haemodynamics and renal dysfunction in endotoxaemia: Effects of nitric oxide synthase inhibition. Br J Pharmacol 1997;121:1824-30.
  29. Chvojka J, Sykora R, Krouzecky A, Radej J, Varnerova V, Karvunidis T, et al. Renal hemodynamic, microcirculatory, metabolic and histopathological responses to peritonitis-induced septic shock in pigs. Crit Care 2008;12:R164.
  30. Chawla LS, Seneff MG, Nelson DR, Williams M, Levy H, Kimmel PL, et al. Elevated plasma concentrations of IL-6 and elevated APACHE II score predict acute kidney injury in patients with severe sepsis. Clin J Am Soc Nephrol.2007;2:22-30.
  31. Taylor LA, Mayeux PR. Nitric oxide generation mediates lipid A- induced oxidant injury in renal proximal tubules. Arch Biochem Biophys 1997;338:129-35.
  32. Johannes T, Mik EG, Klingel K, Dieterich HJ, Unertl KE, Ince C. Low-dose dexamethasone-supplemented fluid resuscitation reverses endotoxin-induced acute renal failure and prevents cortical micro vascular hypoxia. Shock 2009;31:521-8.
  33. Heemskerk S, Masereew R, Russel FG, Pickkers P. Selective iNOS inhibition for the treatment of sepsis-induced acute kidney injury. Nat Rev Nephrol 2009;5,629-40.
  34. Dellinger RP, Carlet JM, Masur H, Gerlach H, Calandra T, Cohen J, et al. Surviving sepsis campaign management guidelines committee: Surviving sepsis campaign guidelines for management of severe sepsis and septic shock. Crit Care Med 2004;32:858-73.
  35. Rivers E, Nguyen B, Havstad S, Ressler J, Muzzin A, Knoblich B, et al. Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med 2001;345:1368-77.
  36. Schortgen F, Lacherade JC, Bruneel F, Cattaneo I, Hemery F, Lemaire F, et al. Effects of hydroxyethylstarch and gelatin on renal function in severe sepsis: A multicentre randomised study. Lancet 2001;357:911-6.
  37. Finfer S, Bellomo R, Boyce N, French J, Myburgh J, Norton R; et al. A comparison of albumin and saline for fluid resuscitation in the intensive care unit. N Engl J Med 2004;350:2247-56.
  38. Di Giantomasso D, Morimatsu H, May CN, Bellomo R. Increasing renal blood flow: Low-dose dopamine or medium-dose norepinephrine. Chest 2004;125:2260-7.
  39. Patel BM, Chittock DR, Russell JA, Walley KR. Beneficial effects of short-term vasopressin infusion during severe septic shock. Anesthesiology 2002;96:576-82.
  40. Russell JA, Walley KR, Singer J, Gordon AC, Hιbert PC, Cooper DJ, et al. Vasopressin versus norepinephrine infusion in patients with septic shock. N Engl J Med 2008;358:877-87.
  41. Burch JM, Moore EE, Moore FA, Franciose R. The abdominal compartment syndrome. Surg Clin North Am 1996;76:833-42
  42. van den Berghe G, Wouters P, Weekers F, Verwaest C, Bruyninckx F, Schetz M, et al. Intensive insulin therapy in the critically ill patients. N Engl J Med 2001;345:1359-67.
  43. van den Berghe G, Wilmer A, Hermans G, Meersseman W, Wouters PJ, Milants I, et al. Intensive insulin therapy in the medical ICU. N Engl J Med 2006;354:449-61.
  44. The NICE-SUGAR Study Investigators. Intensive versus conventional glucose control in critically ill patients. N Engl J Med 2009;360:1283-97.
  45. The Acute Respiratory Distress Syndrome Network: Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. N Engl J Med 2000;342:1301-8.
  46. Imai Y, Parodo J, Kajikawa O, de Perrot M, Fischer S, Edwards V, et al. Injurious mechanical ventilation and end-organ epithelial cell apoptosis and organ dysfunction in an experimental model of acute respiratory distress syndrome. JAMA 2003;289:2104-12.
  47. Morelli A, Ricci Z, Bellomo R, Ronco C, Rocco M, Conti G, et al. Prophylactic fenoldopam for renal protection in sepsis: A randomized, double-blind, placebo-controlled pilot trial. Crit Care Med 2005;33:2451-6.
  48. Gupta A, Williams MD, Macias WL, Molitoris BA, Grinnell BW. Activated protein C and acute kidney injury: Selective targeting of PAR-1. Curr Drug Targets 2009;10:1212-26.
  49. Vail GM, Wang D, Macias WL. In patients with severe sepsisrenal dysfunction is predicted by severe protein C deficiency which is improved by drotrecogin alfa (activated) therapy. Crit Care Med 2006;34:A101.
  50. Ronco C, Kellum JA, Bellomo R, House AA. Potential interventions in sepsis-related acute kidney injury. Clin J Am Soc Nephrol 2008;3:531-44.
  51. Uchino S, Bellomo R, Morimatsu H, Morgera S, Schetz M, Tan I, et al. Continuous renal replacement therapy: A worldwide practice survey: The beginning and ending supportive therapy for the kidney (BEST kidney) investigators. Intensive Care Med 2007;33:1563-50.
  52. Rabindranath K, Adams J, Macleod A, Muirhead N. Intermittent versus continuous renal replacement therapy for acute renal failure in adults. Cochrane Database Syst Rev 2007;3:CD003773.
  53. Ronco C, Bellomo R, Homel P, Brendolan A, Dan M, Piccinni P, et al. Effects of different doses in continuous veno-venous haemofiltration on outcomes of acute renal failure: A prospective randomised trial. Lancet 2000;356:26-30.
  54. VA/NIH Acute Renal Failure Trial Network, Palevsky PM, Zhang JH, O′Connor TZ, Chertow GM, Crowley ST, et al. Intensity of renal support in critically ill patients with acute kidney injury. N Engl J Med 2008;359:7-20.
  55. De Vriese AS, Colardyn FA, Philippe JJ, Vanholder RC, De Sutter JH, Lameire NH. Cytokine removal during continuous hemofiltration in septic patients. J Am Soc Nephrol 1999;10:846-53.
  56. Haase M, Silvester W, Uchino S, Goldsmith D, Davenport P, Tipping P, et al. A pilot study of high-adsorption hemofiltration in human septic shock. Int J Artif Organs 2007;30:108-17.
  57. Cruz DN, Perazella MA, Bellomo R, de Cal M, Polanco N, Corradi V, et al. Effectiveness of polymyxin B-immobilized fiber column in sepsis: A systematic review. Crit Care 2007;11:R47.
  58. Ronco C, Brendolan A, Lonnemann G, Bellomo R, Piccinni P, Digito A, et al. A pilot study of coupled plasma filtration with adsorption in septic shock. Crit Care Med 2002;30:1250-5.
  59. Ronco C, Tetta C, Mariano F, Wratten ML, Bonello M, Bordoni V, et al. Interpreting the mechanisms of continuous renal replacement therapy in sepsis: The peak concentration hypothesis. Artif Organs 2003;27:792-801.
  60. Cole L, Bellomo R, Journois D, Davenport P, Baldwin I, Tipping P. High-volume haemofiltration in human septic shock. Intensive Care Med 2001;27:978-86.
  61. Honore PM, Joannes-Boyau O, Merson L, Boer W, Piette V, Galloy AC, et al. The big bang of hemofiltration: The beginning of a new era in the third millennium for extra-corporeal blood purification. Int J Artif Organs 2006;29:649-59.
  62. Morgera S, Haase M, Kuss T, Vargas-Hein O, Zuckermann-Becker H, Melzer C, et al. Pilot study on the effects of high cutoff hemofiltration on the need for norepinephrine in septic patients with acute renal failure. Crit Care Med 2006;34:2099-104.
  63. Tumlin J, Wali R, Williams W, Murray P, Tolwani AJ, Vinnikova AK, et al. Efficacy and safety of renal tubule cell therapy for acute renal failure. J Am Soc Nephrol 2008;19:1034-40.
  64. Uchino S, Bellomo R, Kellum JA, Morimatsu H, Morgera S, Schetz MR, et al. Beginning and Ending Supportive Therapy for the Kidney (BEST Kidney) investigators writing committee: Patient and kidney survival by dialysis modality in critically ill patients with acute kidney injury. Int J Artif Organs 2007;30:281-92.
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