Sepsis as a cause and consequence of acute kidney injury: Program to Improve Care in Acute Renal Disease

Ravindra L Mehta, Josée Bouchard, Sharon B Soroko, T Alp Ikizler, Emil P Paganini, Glenn M Chertow, Jonathan Himmelfarb, Program to Improve Care in Acute Renal Disease (PICARD) Study Group, Ravindra L Mehta, Josée Bouchard, Sharon B Soroko, T Alp Ikizler, Emil P Paganini, Glenn M Chertow, Jonathan Himmelfarb, Program to Improve Care in Acute Renal Disease (PICARD) Study Group

Abstract

Purpose: Sepsis commonly contributes to acute kidney injury (AKI); however, the frequency with which sepsis develops as a complication of AKI and the clinical consequences of this sepsis are unknown. This study examined the incidence of, and outcomes associated with, sepsis developing after AKI.

Methods: We analyzed data from 618 critically ill patients enrolled in a multicenter observational study of AKI (PICARD). Patients were stratified according to their sepsis status and timing of incident sepsis relative to AKI diagnosis.

Results: We determined the associations among sepsis, clinical characteristics, provision of dialysis, in-hospital mortality, and length of stay (LOS), comparing outcomes among patients according to their sepsis status. Among the 611 patients with data on sepsis status, 174 (28%) had sepsis before AKI, 194 (32%) remained sepsis-free, and 243 (40%) developed sepsis a median of 5 days after AKI. Mortality rates for patients with sepsis developing after AKI were higher than in sepsis-free patients (44 vs. 21%; p < 0.0001) and similar to patients with sepsis preceding AKI (48 vs. 44%; p = 0.41). Compared with sepsis-free patients, those with sepsis developing after AKI were also more likely to be dialyzed (70 vs. 50%; p < 0.001) and had longer LOS (37 vs. 27 days; p < 0.001). Oliguria, higher fluid accumulation and severity of illness scores, non-surgical procedures after AKI, and provision of dialysis were predictors of sepsis after AKI.

Conclusions: Sepsis frequently develops after AKI and portends a poor prognosis, with high mortality rates and relatively long LOS. Future studies should evaluate techniques to monitor for and manage this complication to improve overall prognosis.

Figures

Fig. 1
Fig. 1
Incidence and timing of sepsis in all patients
Fig. 2
Fig. 2
Kaplan–Meier mortality estimates, by sepsis status over hospitalization (p = 0.005 between all groups)
Fig. 3
Fig. 3
Outcomes according to sepsis status
Fig. 4
Fig. 4
In-hospital mortality rate stratified for sepsis and dialysis status

References

    1. 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. Acute renal failure in critically ill patients: a multinational, multicenter study. JAMA. 2005;294:813–818. doi: 10.1001/jama.294.7.813.
    1. Chertow GM, Burdick E, Honour M, Bonventre JV, Bates DW. Acute kidney injury, mortality, length of stay, and costs in hospitalized patients. J Am Soc Nephrol. 2005;16:3365–3370. doi: 10.1681/ASN.2004090740.
    1. Waikar SS, Curhan GC, Wald R, McCarthy EP, Chertow GM. Declining mortality in patients with acute renal failure, 1988 to 2002. J Am Soc Nephrol. 2006;17:1143–1150. doi: 10.1681/ASN.2005091017.
    1. Joannidis M, Metnitz B, Bauer P, Schusterschitz N, Moreno R, Druml W, Metnitz PG. Acute kidney injury in critically ill patients classified by AKIN versus RIFLE using the SAPS 3 database. Intensive Care Med. 2009;35:1692–1702. doi: 10.1007/s00134-009-1530-4.
    1. Joannidis M, Metnitz PG. Epidemiology and natural history of acute renal failure in the ICU. Crit Care Clin. 2005;21:239–249. doi: 10.1016/j.ccc.2004.12.005.
    1. Bagshaw SM, Uchino S, Bellomo R, Morimatsu H, Morgera S, Schetz M, Tan I, Bouman C, Macedo E, Gibney N, Tolwani A, van Oudemans-Straaten HM, Ronco C, Kellum JA. Septic acute kidney injury in critically ill patients: clinical characteristics and outcomes. Clin J Am Soc Nephrol. 2007;2:431–439. doi: 10.2215/CJN.03681106.
    1. Bagshaw SM, Lapinsky S, Dial S, Arabi Y, Dodek P, Wood G, Ellis P, Guzman J, Marshall J, Parrillo JE, Skrobik Y, Kumar A. Acute kidney injury in septic shock: clinical outcomes and impact of duration of hypotension prior to initiation of antimicrobial therapy. Intensive Care Med. 2009;35:871–881. doi: 10.1007/s00134-008-1367-2.
    1. Bagshaw SM, George C, Bellomo R. Early acute kidney injury and sepsis: a multicentre evaluation. Crit Care. 2008;12:R47. doi: 10.1186/cc6948.
    1. Oppert M, Engel C, Brunkhorst FM, Bogatsch H, Reinhart K, Frei U, Eckardt KU, Loeffler M, John S. 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 Transpl. 2008;23:904–909. doi: 10.1093/ndt/gfm610.
    1. Neveu H, Kleinknecht D, Brivet F, Loirat P, Landais P. 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 Transpl. 1996;11:293–299.
    1. Yegenaga I, Hoste E, Van Biesen W, Vanholder R, Benoit D, Kantarci G, Dhondt A, Colardyn F, Lameire N. Clinical characteristics of patients developing ARF due to sepsis/systemic inflammatory response syndrome: results of a prospective study. Am J Kidney Dis. 2004;43:817–824. doi: 10.1053/j.ajkd.2003.12.045.
    1. Hoste EA, Lameire NH, Vanholder RC, Benoit DD, Decruyenaere JM, Colardyn FA. Acute renal failure in patients with sepsis in a surgical ICU: predictive factors, incidence, comorbidity, and outcome. J Am Soc Nephrol. 2003;14:1022–1030. doi: 10.1097/01.ASN.0000059863.48590.E9.
    1. Levy EM, Viscoli CM, Horwitz RI. The effect of acute renal failure on mortality. A cohort analysis. JAMA. 1996;275:1489–1494. doi: 10.1001/jama.275.19.1489.
    1. Mehta RL, Pascual MT, Soroko S, Savage BR, Himmelfarb J, Ikizler TA, Paganini EP, Chertow GM. Spectrum of acute renal failure in the intensive care unit: the PICARD experience. Kidney Int. 2004;66:1613–1621. doi: 10.1111/j.1523-1755.2004.00927.x.
    1. (1992) American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference: definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. Crit Care Med 20:864–874
    1. 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. Pediatric patients with multi-organ dysfunction syndrome receiving continuous renal replacement therapy. Kidney Int. 2005;67:653–658. doi: 10.1111/j.1523-1755.2005.67121.x.
    1. Bouchard J, Soroko SB, Chertow GM, Himmelfarb J, Ikizler TA, Paganini EP, Mehta RL. Fluid accumulation, survival and recovery of kidney function in critically ill patients with acute kidney injury. Kidney Int. 2009;76:422–427. doi: 10.1038/ki.2009.159.
    1. Vincent JL, Moreno R, Takala J, Willatts S, De Mendonca A, Bruining H, Reinhart CK, Suter PM, Thijs LG. The SOFA (Sepsis-related Organ Failure Assessment) score to describe organ dysfunction/failure. On behalf of the Working Group on Sepsis-Related Problems of the European Society of Intensive Care Medicine. Intensive Care Med. 1996;22:707–710. doi: 10.1007/BF01709751.
    1. Lassnigg A, Schmid ER, Hiesmayr M, Falk C, Druml W, Bauer P, Schmidlin D. Impact of minimal increases in serum creatinine on outcome in patients after cardiothoracic surgery: do we have to revise current definitions of acute renal failure? Crit Care Med. 2008;36:1129–1137. doi: 10.1097/CCM.0b013e318169181a.
    1. Lassnigg A, Schmidlin D, Mouhieddine M, Bachmann LM, Druml W, Bauer P, Hiesmayr M. Minimal changes of serum creatinine predict prognosis in patients after cardiothoracic surgery: a prospective cohort study. J Am Soc Nephrol. 2004;15:1597–1605. doi: 10.1097/01.ASN.0000130340.93930.DD.
    1. Chertow GM, Soroko SH, Paganini EP, Cho KC, Himmelfarb J, Ikizler TA, Mehta RL. Mortality after acute renal failure: models for prognostic stratification and risk adjustment. Kidney Int. 2006;70:1120–1126. doi: 10.1038/sj.ki.5001579.
    1. Payen D, de Pont AC, Sakr Y, Spies C, Reinhart K, Vincent JL. A positive fluid balance is associated with a worse outcome in patients with acute renal failure. Crit Care. 2008;12:R74. doi: 10.1186/cc6916.
    1. Vincent JL, Sakr Y, Sprung CL, Ranieri VM, Reinhart K, Gerlach H, Moreno R, Carlet J, Le Gall JR, Payen D. Sepsis in European intensive care units: results of the SOAP study. Crit Care Med. 2006;34:344–353. doi: 10.1097/01.CCM.0000194725.48928.3A.
    1. MacFie J, O’Boyle C, Mitchell CJ, Buckley PM, Johnstone D, Sudworth P. Gut origin of sepsis: a prospective study investigating associations between bacterial translocation, gastric microflora, and septic morbidity. Gut. 1999;45:223–228. doi: 10.1136/gut.45.2.223.
    1. Gatt M, Reddy BS, MacFie J. Review article: bacterial translocation in the critically ill—evidence and methods of prevention. Aliment Pharmacol Ther. 2007;25:741–757. doi: 10.1111/j.1365-2036.2006.03174.x.
    1. Brusselaers N, Monstrey S, Colpaert K, Decruyenaere J, Blot SI, Hoste EA (2010) Outcome of acute kidney injury in severe burns: a systematic review and meta-analysis. Intensive Care Med 36:915–925
    1. Himmelfarb J, Le P, Klenzak J, Freedman S, McMenamin ME, Ikizler TA. Impaired monocyte cytokine production in critically ill patients with acute renal failure. Kidney Int. 2004;66:2354–2360. doi: 10.1111/j.1523-1755.2004.66023.x.
    1. Moore I, Bhat R, Hoenich NA, Kilner AJ, Prabhu M, Orr KE, Kanagasundaram NS. A microbiological survey of bicarbonate-based replacement circuits in continuous veno-venous hemofiltration. Crit Care Med. 2009;37:496–500. doi: 10.1097/CCM.0b013e3181957987.
    1. Chertow GM, Pascual MT, Soroko S, Savage BR, Himmelfarb J, Ikizler TA, Paganini EP, Mehta RL. Reasons for non-enrollment in a cohort study of ARF: the Program to Improve Care in Acute Renal Disease (PICARD) experience and implications for a clinical trials network. Am J Kidney Dis. 2003;42:507–512. doi: 10.1016/S0272-6386(03)00745-5.
    1. Bone RC, Fisher CJ, Jr, Clemmer TP, Slotman GJ, Metz CA, Balk RA. Sepsis syndrome: a valid clinical entity. Methylprednisolone Severe Sepsis Study Group. Crit Care Med. 1989;17:389–393. doi: 10.1097/00003246-198905000-00002.
    1. Himmelfarb J, McMonagle E, Freedman S, Klenzak J, McMenamin E, Le P, Pupim LB, Ikizler TA, The PG Oxidative stress is increased in critically ill patients with acute renal failure. J Am Soc Nephrol. 2004;15:2449–2456. doi: 10.1097/01.ASN.0000138232.68452.3B.
    1. Basi S, Pupim LB, Simmons EM, Sezer MT, Shyr Y, Freedman S, Chertow GM, Mehta RL, Paganini E, Himmelfarb J, Ikizler TA. Insulin resistance in critically ill patients with acute renal failure. Am J Physiol Renal Physiol. 2005;289:F259–F264. doi: 10.1152/ajprenal.00002.2005.

Source: PubMed

Sponsors and Collaborators

Medical Conditions

Drug Interventions

3
Subscribe