Intensive Care Medicine

, Volume 35, Issue 5, pp 871–881 | Cite as

Acute kidney injury in septic shock: clinical outcomes and impact of duration of hypotension prior to initiation of antimicrobial therapy

  • Sean M. Bagshaw
  • Stephen Lapinsky
  • Sandra Dial
  • Yaseen Arabi
  • Peter Dodek
  • Gordon Wood
  • Paul Ellis
  • Jorge Guzman
  • John Marshall
  • Joseph E. Parrillo
  • Yoanna Skrobik
  • Anand Kumar
  • The Cooperative Antimicrobial Therapy of Septic Shock (CATSS) Database Research Group



To describe the incidence and outcomes associated with early acute kidney injury (AKI) in septic shock and explore the association between duration from hypotension onset to effective antimicrobial therapy and AKI.


Retrospective cohort study.


A total of 4,532 adult patients with septic shock from 1989 to 2005.


Intensive care units of 22 academic and community hospitals in Canada, the United States and Saudi Arabia.

Measurements and main results

In total, 64.4% of patients with septic shock developed early AKI (i.e., within 24 h after onset of hypotension). By RIFLE criteria, 16.3% had risk, 29.4% had injury and 18.7% had failure. AKI patients were older, more likely female, with more co-morbid disease and greater severity of illness. Of 3,373 patients (74.4%) with hypotension prior to receiving effective antimicrobial therapy, the median (IQR) time from hypotension onset to antimicrobial therapy was 5.5 h (2.0–13.3). Patients with AKI were more likely to have longer delays to receiving antimicrobial therapy compared to those with no AKI [6.0 (2.3–15.3) h for AKI vs. 4.3 (1.5–10.8) h for no AKI, P < 0.0001). A longer duration to antimicrobial therapy was also associated an increase in odds of AKI [odds ratio (OR) 1.14, 95% CI 1.10–1.20, P < 0.001, per hour (log-transformed) delay]. AKI was associated with significantly higher odds of death in both ICU (OR 1.73, 95% CI 1.60–1.9, P < 0.0001) and hospital (OR 1.62, 95% CI, 1.5–1.7, P < 0.0001). By Cox proportional hazards analysis, including propensity score-adjustment, each RIFLE category was independently associated with a greater hazard ratio for death (risk 1.31; injury 1.45; failure 1.56).


Early AKI is common in septic shock. Delays to appropriate antimicrobial therapy may contribute to significant increases in the incidence of AKI. Survival was considerably lower for septic shock associated with early AKI, with increasing severity of AKI, and with increasing delays to appropriate antimicrobial therapy.


Acute kidney injury Acute renal failure Critically ill Sepsis Septic shock Mortality Incidence Multi-center 



Dr. Bagshaw is supported by a Clinical Investigator Award from the Alberta Heritage Foundation for Medical Research. Dr. Kumar received initial competitive grant support for the development of the septic shock database from Health Sciences Centre Department of Research and Health Sciences Centre Foundation. Subsequent database development was also supported through unrestricted grants from Astellas Pharma Inc., Eli-Lilly and Co., Pfizer Inc., Bayer Inc., Merck and Co., Wyeth Pharmaceuticals, Bristol-Myers Squibb Co., and Astra-Zeneca Inc.


  1. 1.
    Bagshaw SM, Laupland KB, Doig CJ, Mortis G, Fick GH, Mucenski M, Godinez-Luna T, Svenson LW, Rosenal T (2005) Prognosis for long-term survival and renal recovery in critically ill patients with severe acute renal failure: a population-based study. Crit Care 9:R700–R709PubMedCrossRefGoogle Scholar
  2. 2.
    Korkeila M, Ruokonen E, Takala J (2000) Costs of care, long-term prognosis and quality of life in patients requiring renal replacement therapy during intensive care. Intensive Care Med 26:1824–1831PubMedCrossRefGoogle Scholar
  3. 3.
    Metnitz PG, Krenn CG, Steltzer H, Lang T, Ploder J, Lenz K, Le Gall JR, Druml W (2002) Effect of acute renal failure requiring renal replacement therapy on outcome in critically ill patients. Crit Care Med 30:2051–2058PubMedCrossRefGoogle Scholar
  4. 4.
    Uchino S, Kellum JA, Bellomo R, Doig GS, Morimatsu H, Morgera S, Schetz M, Tan I, Bouman C, Macedo E, Gibney N, Tolwani A, Ronco C (2005) Acute renal failure in critically ill patients: a multinational, multicenter study. JAMA 294:813–818PubMedCrossRefGoogle Scholar
  5. 5.
    Bagshaw SM, George C, Dinu I, Bellomo R (2008) A multi-centre evaluation of the Rifle criteria for early acute kidney injury in critically ill patients. Nephrol Dial Transplant 23:1203–1210PubMedCrossRefGoogle Scholar
  6. 6.
    Ostermann M, Chang RW (2007) Acute kidney injury in the intensive care unit according to RIFLE. Crit Care Med 35:1837–1843PubMedCrossRefGoogle Scholar
  7. 7.
    Bagshaw SM, George C, Bellomo R (2007) Changes in the incidence and outcome for early acute kidney injury in a cohort of Australian intensive care units. Crit Care 11:R68PubMedCrossRefGoogle Scholar
  8. 8.
    Xue JL, Daniels F, Star RA, Kimmel PL, Eggers PW, Molitoris BA, Himmelfarb J, Collins AJ (2006) Incidence and mortality of acute renal failure in Medicare beneficiaries, 1992 to 2001. J Am Soc Nephrol 17:1135–1142PubMedCrossRefGoogle Scholar
  9. 9.
    Rangel-Frausto MS, Pittet D, Costigan M, Hwang T, Davis CS, Wenzel RP (1995) The natural history of the systemic inflammatory response syndrome (SIRS). A prospective study. JAMA 273:117–123PubMedCrossRefGoogle Scholar
  10. 10.
    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 2:431–439PubMedCrossRefGoogle Scholar
  11. 11.
    Hoste EA, Lameire NH, Vanholder RC, Benoit DD, Decruyenaere JM, Colardyn FA (2003) Acute renal failure in patients with sepsis in a surgical ICU: predictive factors, incidence, comorbidity, and outcome. J Am Soc Nephrol 14:1022–1030PubMedCrossRefGoogle Scholar
  12. 12.
    Lopes JA, Jorge S, Resina C, Santos C, Pereira A, Neves J, Antunes F, Prata MM (2007) Acute renal failure in patients with sepsis. Crit Care 11:411PubMedCrossRefGoogle Scholar
  13. 13.
    Neveu H, Kleinknecht D, Brivet F, Loirat P, Landais P (1996) Prognostic factors in acute renal failure due to sepsis. Results of a prospective multicentre study. The French Study Group on Acute Renal Failure. Nephrol Dial Transplant 11:293–299PubMedGoogle Scholar
  14. 14.
    Oppert M, Engel C, Brunkhorst FM, Bogatsch H, Reinhart K, Frei U, Eckardt KU, Loeffler M, John S (2008) Acute renal failure in patients with severe sepsis and septic shock a significant independent risk factor for mortality: results from the German Prevalence Study. Nephrol Dial Transplant 23:904–909PubMedCrossRefGoogle Scholar
  15. 15.
    Vincent JL, Sakr Y, Sprung CL, Ranieri VM, Reinhart K, Gerlach H, Moreno R, Carlet J, Le Gall JR, Payen D (2006) Sepsis in European intensive care units: results of the SOAP study. Crit Care Med 34:344–353PubMedCrossRefGoogle Scholar
  16. 16.
    Yegenaga I, Hoste E, Van Biesen W, Vanholder R, Benoit D, Kantarci G, Dhondt A, Colardyn F, Lameire N (2004) Clinical characteristics of patients developing ARF due to sepsis/systemic inflammatory response syndrome: results of a prospective study. Am J Kidney Dis 43:817–824PubMedCrossRefGoogle Scholar
  17. 17.
    Bagshaw SM, George C, Bellomo R (2008) Early acute kidney injury and sepsis: a multicentre evaluation. Crit Care 12:R47PubMedCrossRefGoogle Scholar
  18. 18.
    Wan L, Bellomo R, Di Giantomasso D, Ronco C (2003) The pathogenesis of septic acute renal failure. Curr Opin Crit Care 9:496–502PubMedCrossRefGoogle Scholar
  19. 19.
    Bellomo R, Bagshaw S, Langenberg C, Ronco C (2007) Pre-renal azotemia: a flawed paradigm in critically ill septic patients? Contrib Nephrol 156:1–9PubMedCrossRefGoogle Scholar
  20. 20.
    Langenberg C, Wan L, Bagshaw SM, Egi M, May CN, Bellomo R (2006) Urinary biochemistry in experimental septic acute renal failure. Nephrol Dial Transplant 21:3389–3397PubMedCrossRefGoogle Scholar
  21. 21.
    Langenberg C, Wan L, Egi M, May CN, Bellomo R (2006) Renal blood flow in experimental septic acute renal failure. Kidney Int 69:1996–2002PubMedCrossRefGoogle Scholar
  22. 22.
    Licari E, Calzavacca P, Ronco C, Bellomo R (2007) Fluid resuscitation and the septic kidney: the evidence. Contrib Nephrol 156:167–177PubMedCrossRefGoogle Scholar
  23. 23.
    Rivers E, Nguyen B, Havstad S, Ressler J, Muzzin A, Knoblich B, Peterson E, Tomlanovich M (2001) Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med 345:1368–1377PubMedCrossRefGoogle Scholar
  24. 24.
    Dellinger RP, Levy MM, Carlet JM, Bion J, Parker MM, Jaeschke R, Reinhart K, Angus DC, Brun-Buisson C, Beale R, Calandra T, Dhainaut JF, Gerlach H, Harvey M, Marini JJ, Marshall J, Ranieri M, Ramsay G, Sevransky J, Thompson BT, Townsend S, Vender JS, Zimmerman JL, Vincent JL (2008) Surviving Sepsis Campaign: International guidelines for management of severe sepsis and septic shock: 2008. Intensive Care Med 34:17–60PubMedCrossRefGoogle Scholar
  25. 25.
    Kumar A, Roberts D, Wood KE, Light B, Parrillo JE, Sharma S, Suppes R, Feinstein D, Zanotti S, Taiberg L, Gurka D, Kumar A, Cheang M (2006) Duration of hypotension before initiation of effective antimicrobial therapy is the critical determinant of survival in human septic shock. Crit Care Med 34:1589–1596PubMedCrossRefGoogle Scholar
  26. 26.
    Bone RC, Balk RA, Cerra FB, Dellinger RP, Fein AM, Knaus WA, Schein RM, Sibbald WJ (1992) Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. The ACCP/SCCM Consensus Conference Committee. American College of Chest Physicians/Society of Critical Care Medicine. Chest 101:1644–1655PubMedCrossRefGoogle Scholar
  27. 27.
    Levy MM, Fink MP, Marshall JC, Abraham E, Angus D, Cook D, Cohen J, Opal SM, Vincent JL, Ramsay G (2003) 2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions Conference. Crit Care Med 31:1250–1256PubMedCrossRefGoogle Scholar
  28. 28.
    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–R212PubMedCrossRefGoogle Scholar
  29. 29.
    Knaus WA, Draper EA, Wagner DP, Zimmerman JE (1985) APACHE II: a severity of disease classification system. Crit Care Med 13:818–829PubMedCrossRefGoogle Scholar
  30. 30.
    Uchino S, Doig GS, Bellomo R, Morimatsu H, Morgera S, Schetz M, Tan I, Bouman C, Nacedo E, Gibney N, Tolwani A, Ronco C, Kellum JA (2004) Diuretics and mortality in acute renal failure. Crit Care Med 32:1669–1677PubMedCrossRefGoogle Scholar
  31. 31.
    Kumar A, Haery C, Paladugu B, Kumar A, Symeoneides S, Taiberg L, Osman J, Trenholme G, Opal SM, Goldfarb R, Parrillo JE (2006) The duration of hypotension before the initiation of antibiotic treatment is a critical determinant of survival in a murine model of Escherichia coli septic shock: association with serum lactate and inflammatory cytokine levels. J Infect Dis 193:251–258PubMedCrossRefGoogle Scholar
  32. 32.
    Angus DC, Linde-Zwirble WT, Lidicker J, Clermont G, Carcillo J, Pinsky MR (2001) Epidemiology of severe sepsis in the United States: analysis of incidence, outcome, and associated costs of care. Crit Care Med 29:1303–1310PubMedCrossRefGoogle Scholar
  33. 33.
    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 348:1546–1554PubMedCrossRefGoogle Scholar
  34. 34.
    Brun-Buisson C, Meshaka P, Pinton P, Vallet B (2004) EPISEPSIS: a reappraisal of the epidemiology and outcome of severe sepsis in French intensive care units. Intensive Care Med 30:580–588PubMedCrossRefGoogle Scholar
  35. 35.
    Brivet FG, Kleinknecht DJ, Loirat P, Landais PJ (1996) Acute renal failure in intensive care units–causes, outcome, and prognostic factors of hospital mortality; a prospective, multicenter study. French Study Group on Acute Renal Failure. Crit Care Med 24:192–198PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2008

Authors and Affiliations

  • Sean M. Bagshaw
    • 1
  • Stephen Lapinsky
    • 2
  • Sandra Dial
    • 3
  • Yaseen Arabi
    • 4
  • Peter Dodek
    • 5
  • Gordon Wood
    • 6
  • Paul Ellis
    • 7
  • Jorge Guzman
    • 8
  • John Marshall
    • 9
  • Joseph E. Parrillo
    • 10
  • Yoanna Skrobik
    • 11
  • Anand Kumar
    • 12
  • The Cooperative Antimicrobial Therapy of Septic Shock (CATSS) Database Research Group
  1. 1.Division of Critical Care MedicineUniversity of AlbertaEdmontonCanada
  2. 2.Section of Critical Care MedicineMount Sinai HospitalTorontoCanada
  3. 3.Section of Critical Care MedicineSir Mortimer B. Davis Jewish General HospitalMontrealCanada
  4. 4.Department of Critical CareNational Guard HospitalRiyadhSaudi Arabia
  5. 5.Section of Critical Care MedicineSt. Paul’s Hospital, University of British ColumbiaVancouverCanada
  6. 6.Critical Care MedicineRoyal Jubilee and Victoria General Hospitals, Vancouver Island Health AuthorityVictoriaCanada
  7. 7.Department of Emergency Medicine, United Health NetworkUniversity of TorontoTorontoCanada
  8. 8.Section of Critical Care MedicineHarper Hospital, Wayne State UniversityDetroitUSA
  9. 9.Section of Critical Care MedicineSt. Michael’s HospitalTorontoCanada
  10. 10.Department of Medicine, Robert Wood Johnson Medical School, UMDNJCooper Hospital, University Medical CenterCamdenUSA
  11. 11.Section of Critical Care MedicineHôpital Maisonneuve RosemontMontrealCanada
  12. 12.Section of Critical Care Medicine, Section of Infectious Diseases, Health Sciences Centre JJ 399University of ManitobaWinnipegCanada

Personalised recommendations