Cómo abordarlo basados en las evidencias disponibles | 08 DIC 19

Daño renal agudo asociado a sepsis

Este artículo resume la evidencia pertinente, centrándose en los factores de riesgo, el diagnóstico temprano, el tratamiento y las consecuencias alejadas del DRA-AS.
Autor/a: Poston JT, Koyner JL BMJ 2019;364:k4891
INDICE:  1. Página 1 | 2. Referencias bibliográficas
Referencias bibliográficas

Singer M, Deutschman CS, Seymour CW, et al. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA 2016; 315:801-10. 10.1001/jama.2016.0287 pmid:26903338.

2 Shankar-Hari M, Phillips GS, Levy ML, et al. Sepsis Definitions Task Force. Developing a New Definition and Assessing New Clinical Criteria for Septic Shock: For the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA 2016; 315:775-87. 10.1001/jama.2016.0289 pmid:26903336.

3 Bone RC, Balk RA, Cerra FB, et al. The ACCP/SCCM Consensus Conference Committee. American College of Chest Physicians/Society of Critical Care Medicine. Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. Chest 1992; 101:1644-55. 10.1378/chest.101.6.1644 pmid: 1303622.

4 Levy MM, Fink MP, Marshall JC, et al. SCCM/ESICM/ACCP/ATS/SIS. 2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions Conference. Crit Care Med 2003; 31:1250-6. 10.1097/01. CCM.0000050454.01978.3B pmid:12682500.

5 Mehta RL, Kellum JA, Shah SV, et al. Acute Kidney Injury Network. Acute Kidney Injury Network: report of an initiative to improve outcomes in acute kidney injury. Crit Care 2007; 11:R31. 10.1186/ cc5713 pmid:17331245.

6 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. 10.1186/cc2872 pmid: 15312219.

7 KDIGO. Kidney Disease: Improving Global Outcomes (KDIGO) Acute Kidney Injury Work Group. KDIGO Clinical Practice Guideline for Acute Kidney Injury. Kidney Int Suppl 2012; 2:1-138.

8 Gotts JE, Matthay MA. Sepsis: pathophysiology and clinical management. BMJ 2016; 353:i1585. 10.1136/bmj. i1585 pmid: 27217054.

9 Sprung CL, Sakr Y, Vincent JL, et al. An evaluation of systemic inflammatory response syndrome signs in the Sepsis Occurrence In Acutely Ill Patients (SOAP) study. Intensive Care Med 2006; 32:421-7. 10.1007/s00134-005-0039-8 pmid: 16479382.

10 Alberti C, Brun-Buisson C, Goodman SV, et al. European Sepsis Group. Influence of systemic inflammatory response syndrome and sepsis on outcome of critically ill infected patients. Am J Respir Crit Care Med 2003; 168:77-84. 10.1164/rccm.200208-785OC pmid: 12702548.

11 Vincent JL, Opal SM, Marshall JC, Tracey KJ. Sepsis definitions: time for change. Lancet 2013; 381:774-5. 10.1016/S0140-6736(12)61815- 7 pmid: 23472921.

12 Vincent JL, de Mendonça A, Cantraine F, et al. Use of the SOFA score to assess the incidence of organ dysfunction/failure in intensive care units: results of a multicenter, prospective study. Working group on “sepsis-related problems” of the European Society of Intensive Care Medicine. Crit Care Med 1998; 26:1793-800. 10.1097/00003246-199811000- 00016 pmid: 9824069.

13 Ferreira FL, Bota DP, Bross A, Mélot C, Vincent JL. Serial evaluation of the SOFA score to predict outcome in critically ill patients. JAMA 2001; 286:1754-8. 10.1001/jama.286.14.1754 pmid: 11594901.

14 Churpek MM, Snyder A, Han X, et al. Quick Sepsis-related Organ Failure Assessment, Systemic Inflammatory Response Syndrome, and Early Warning Scores for Detecting Clinical Deterioration in Infected Patients outside the Intensive Care Unit. Am J Respir Crit Care Med 2017; 195:906- 11. 10.1164/rccm.201604-0854OC pmid: 27649072.

15 Mao Q, Jay M, Hoffman JL, et al. Multicentre validation of a sepsis prediction algorithm using only vital sign data in the emergency department, general ward and ICU. BMJ Open 2018;8: e017833. 10.1136/ bmjopen-2017-017833 pmid: 29374661.

16 Brivet FG, Kleinknecht DJ, Loirat P, Landais PJ. French Study Group on Acute Renal Failure. Acute renal failure in intensive care units--causes, outcome, and prognostic factors of hospital mortality; a prospective, multicenter study. Crit Care Med 1996; 24:192-8. 10.1097/00003246-199602000- 00003 pmid:8605788.

17 Chertow GM, Levy EM, Hammermeister KE, Grover F, Daley J. Independent association between acute renal failure and mortality following cardiac surgery. Am J Med 1998; 104:343-8. 10.1016/S0002-9343(98)00058- 8 pmid:9576407.

18 de Mendonça A, Vincent JL, Suter PM, et al. Acute renal failure in the ICU: risk factors and outcome evaluated by the SOFA score. Intensive Care Med 2000; 26:915-21. 10.1007/s001340051281 pmid:10990106.

19 Joannidis M, Metnitz B, Bauer P, et al. Acute kidney injury in critically ill patients classified by AKIN versus RIFLE using the SAPS 3 database. Intensive Care Med 2009; 35:1692-702. 10.1007/s00134-009-1530- 4 pmid:19547955.

20 Thakar CV, Christianson A, Freyberg R, Almenoff P, Render ML. Incidence and outcomes of acute kidney injury in intensive care units: a Veterans Administration study. Crit Care Med 2009; 37:2552-8. 10.1097/ CCM.0b013e3181a5906f pmid: 19602973.

21 Kellum JA, Lameire N. KDIGO AKI Guideline Work Group. Diagnosis, evaluation, and management of acute kidney injury: a KDIGO summary (Part 1). Crit Care 2013; 17:204. 10.1186/cc11454 pmid: 23394211.

22 Hoste EA, Bagshaw SM, Bellomo R, et al. Epidemiology of acute kidney injury in critically ill patients: the multinational AKI-EPI study. Intensive Care Med 2015; 41:1411-23. 10.1007/s00134-015-3934- 7 pmid: 26162677.

23 Endre ZH, Kellum JA, Di Somma S, et al. Differential diagnosis of AKI in clinical practice by functional and damage biomarkers: workgroup statements from the tenth Acute Dialysis Quality Initiative Consensus Conference. Contrib Nephrol 2013; 182:30-44. 10.1159/000349964 pmid:23689654.

24 Chawla LS, Bellomo R, Bihorac A, et al. Acute Disease Quality Initiative Workgroup 16.Acute kidney disease and renal recovery: consensus report of the Acute Disease Quality Initiative (ADQI) 16 Workgroup. Nat Rev Nephrol 2017; 13:241-57. 10.1038/nrneph.2017.2 pmid: 28239173.

25 Uchino S, Kellum JA, Bellomo R, et al. Beginning and Ending Supportive Therapy for the Kidney (BEST Kidney) Investigators. Acute renal failure in critically ill patients: a multinational, multicenter study. JAMA 2005; 294:813-8. 10.1001/jama.294.7.813 pmid: 16106006.

26 Yegenaga I, Hoste E, Van Biesen W, et al. Clinical characteristics of patients developing ARF due to sepsis/systemic inflammatory response syndrome: results of a prospective study. Am J Kidney Dis 2004; 43:817-24. 10.1053/j.ajkd.2003.12.045 pmid: 15112172.

27 Bagshaw SM, Lapinsky S, Dial S, et al. Cooperative Antimicrobial Therapy of Septic Shock (CATSS) Database Research Group. Acute kidney injury in septic shock: clinical outcomes and impact of duration of hypotension prior to initiation of antimicrobial therapy. Intensive Care Med 2009; 35:871-81. 10.1007/s00134-008-1367-2 pmid: 19066848.

28 Perner A, Cecconi M, Cronhjort M, et al. Expert statement for the management of hypovolemia in sepsis. Intensive Care Med 2018; 44:791- 8. 10.1007/s00134-018-5177-x pmid: 29696295.

29 Mehta RL, Bouchard J, Soroko SB, et al. Program to Improve Care in Acute Renal Disease (PICARD) Study Group. Sepsis as a cause and consequence of acute kidney injury: Program to Improve Care in Acute Renal Disease. Intensive Care Med 2011; 37:241-8. 10.1007/s00134-010-2089- 9 pmid: 21152901.

30 Morrell ED, Kellum JA, Pastor-Soler NM, Hallows KR. Septic acute kidney injury: molecular mechanisms and the importance of stratification and targeting therapy. Crit Care 2014; 18:501. 10.1186/s13054-014-0501- 5 pmid: 25575158.

31 Bagshaw SM, Uchino S, Bellomo R, et al. Beginning and Ending Supportive Therapy for the Kidney (BEST Kidney) Investigators. Septic acute kidney injury in critically ill patients: clinical characteristics and outcomes. Clin J Am Soc Nephrol 2007; 2:431-9. 10.2215/CJN.03681106 pmid: 17699448.

32 Bouchard J, Acharya A, Cerda J, et al. A Prospective International Multicenter Study of AKI in the Intensive Care Unit. Clin J Am Soc Nephrol 2015; 10:1324-31. 10.2215/CJN.04360514 pmid: 26195505.

33 Martin GS, Mannino DM, Eaton S, Moss M. The epidemiology of sepsis in the United States from 1979 through 2000. N Engl J Med 2003; 348:1546-54. 10.1056/NEJMoa022139 pmid:12700374.

34 McPherson D, Griffiths C, Williams M, et al. Sepsis-associated mortality in England: an analysis of multiple cause of death data from 2001 to 2010. BMJ Open 2013; 3:e002586. 10.1136/ bmjopen-2013-002586 pmid: 23913771.

35 Kaukonen KM, Bailey M, Suzuki S, Pilcher D, Bellomo R. Mortality related to severe sepsis and septic shock among critically ill patients in Australia and New Zealand, 2000-2012. JAMA 2014; 311:1308-16. 10.1001/ jama.2014.2637 pmid: 24638143.

36 Kadri SS, Rhee C, Strich JR, et al. Estimating Ten-Year Trends in Septic Shock Incidence and Mortality in United States Academic Medical Centers Using Clinical Data. Chest 2017; 151:278-85. 10.1016/j. chest.2016.07.010 pmid: 27452768.

37 Chertow GM, Soroko SH, Paganini EP, et al. Mortality after acute renal failure: models for prognostic stratification and risk adjustment. Kidney Int 2006; 70:1120-6. 10.1038/sj.ki.5001579 pmid:16850028.

38 Thakar CV, Liangos O, Yared JP, et al. ARF after open-heart surgery: Influence of gender and race. Am J Kidney Dis 2003; 41:742-51. 10.1016/S0272- 6386(03)00021-0 pmid: 12666060.

39 Pannu N, James M, Hemmelgarn BR, Dong J, Tonelli M, Klarenbach S. Alberta Kidney Disease Network. Modification of outcomes after acute kidney injury by the presence of CKD. Am J Kidney Dis 2011; 58:206-13. 10.1053/j.ajkd.2011.01.028 pmid : 21496979.

40 Bagshaw SM, Laupland KB, Doig CJ, et al. Prognosis for long-term survival and renal recovery in critically ill patients with severe acute renal failure: a population-based study. Crit Care 2005; 9:R700-9. 10.1186/ cc3879 pmid: 16280066.

41 Wiedermann CJ, Wiedermann W, Joannidis M. Hypoalbuminemia and acute kidney injury: a meta-analysis of observational clinical studies. Intensive Care Med 2010; 36:1657-65. 10.1007/s00134-010- 1928-z pmid: 20517593.

42 Lima RS, Marques CN, Silva Júnior GB, et al. Comparison between early and delayed acute kidney injury secondary to infectious disease in the intensive care unit. Int Urol Nephrol 2008; 40:731-9. 10.1007/s11255-008-9352- 9 pmid: 18368509.

43 Rewa O, Bagshaw SM. Acute kidney injury-epidemiology, outcomes and economics. Nat Rev Nephrol 2014; 10:193-207. 10.1038/ nrneph.2013.282 pmid:24445744.

44 Hobson C, Ozrazgat-Baslanti T, Kuxhausen A, et al. Cost and Mortality Associated With Postoperative Acute Kidney Injury. Ann Surg 2015;261:1207-14. 10.1097/ SLA.0000000000000732 pmid: 24887982.

45 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; 16:3365-70. 10.1681/ ASN.2004090740 pmid: 16177006.

46 Bernier-Jean A, Beaubien-Souligny W, Goupil R, et al. Diagnosis and outcomes of acute kidney injury using surrogate and imputation methods for missing preadmission creatinine values. BMC Nephrol 2017; 18:141. 10.1186/s12882-017-0552-3 pmid: 28454562.

47 Zhao B, Lu Q, Cheng Y, et al. TRIBE-AKI Consortium *. A Genome-Wide Association Study to Identify Single-Nucleotide Polymorphisms for Acute Kidney Injury. Am J Respir Crit Care Med 2017; 195:482-90. 10.1164/ rccm.201603-0518OC pmid: 27576016.

48 Jin K, Murugan R, Sileanu FE, et al. Intensive Monitoring of Urine Output Is Associated With Increased Detection of Acute Kidney Injury and Improved Outcomes. Chest 2017; 152:972-9. 10.1016/j. chest.2017.05.011 pmid: 28527880.

49 Kellum JA, Sileanu FE, Murugan R, Lucko N, Shaw AD, Clermont G. Classifying AKI by Urine Output versus Serum Creatinine Level. J Am Soc Nephrol 2015; 26:2231-8. 10.1681/ASN.2014070724 pmid: 25568178.

50 Quan S, Pannu N, Wilson T, et al. Prognostic implications of adding urine output to serum creatinine measurements for staging of acute kidney injury after major surgery: a cohort study. Nephrol Dial Transplant 2016; 31:2049- 56. 10.1093/ndt/gfw374 pmid: 27941063.

51 Chawla LS, Dommu A, Berger A, Shih S, Patel SS. Urinary sediment cast scoring index for acute kidney injury: a pilot study. Nephron Clin Pract 2008; 110:c145-50. 10.1159/000166605 pmid: 18953176.

52 Perazella MA, Coca SG, Hall IE, Iyanam U, Koraishy M, Parikh CR. Urine microscopy is associated with severity and worsening of acute kidney injury in hospitalized patients. Clin J Am Soc Nephrol 2010; 5:402-8. 10.2215/ CJN.06960909 pmid: 20089493.

53 Bagshaw SM, Haase M, Haase-Fielitz A, Bennett M, Devarajan P, Bellomo R. A prospective evaluation of urine microscopy in septic and non-septic acute kidney injury. Nephrol Dial Transplant 2012; 27:582-8. 10.1093/ndt/ gfr331 pmid: 21669886.

54 Neyra JA, Manllo J, Li X, Jacobsen G, Yee J, Yessayan L. AKICI Study Group. Association of de novo dipstick albuminuria with severe acute kidney injury in critically ill septic patients. Nephron Clin Pract 2014; 128:373-80. 10.1159/000368902 pmid: 25591812.

55 Neyra JA, Li X, Yessayan L, Adams-Huet B, Yee J, Toto RD. Acute Kidney Injury in Critical Illness Study Group. Dipstick albuminuria and acute kidney injury recovery in critically ill septic patients. Nephrology (Carlton) 2016; 21:512- 8. 10.1111/nep.12637 pmid: 26421662.

56 McMahon BA, Koyner JL. Risk Stratification for Acute Kidney Injury: Are Biomarkers Enough? Adv Chronic Kidney Dis 2016;23:167-78. 10.1053/j. ackd.2016.03.001 pmid: 27113693.

57 Huen SC, Parikh CR. Predicting acute kidney injury after cardiac surgery: a systematic review. Ann Thorac Surg 2012; 93:337-47. 10.1016/j. athoracsur.2011.09.010 pmid: 22186469.

58 Mehta RH, Grab JD, O’Brien SM, et al. Society of Thoracic Surgeons National Cardiac Surgery Database Investigators. Bedside tool for predicting the risk of postoperative dialysis in patients undergoing cardiac surgery. Circulation 2006; 114:2208-16, quiz 2208. 10.1161/ CIRCULATIONAHA.106.635573 pmid: 17088458.

59 Palomba H, de Castro I, Neto AL, Lage S, Yu L. Acute kidney injury prediction following elective cardiac surgery: AKICS Score. Kidney Int 2007; 72:624- 31. 10.1038/sj.ki.5002419 pmid: 17622275.

60 Thakar CV, Arrigain S, Worley S, Yared JP, Paganini EP. A clinical score to predict acute renal failure after cardiac surgery. J Am Soc Nephrol 2005; 16:162-8. 10.1681/ASN.2004040331 pmid: 15563569.

61 Wijeysundera DN, Karkouti K, Dupuis JY, et al. Derivation and validation of a simplified predictive index for renal replacement therapy after cardiac surgery. JAMA 2007; 297:1801-9. 10.1001/ jama.297.16.1801 pmid: 17456822.

62 Uchino S, Bellomo R, Morimatsu H, et al. Beginning and Ending Supportive Therapy for the Kidney (B.E.S.T. Kidney) Investigators. External validation of severity scoring systems for acute renal failure using a multinational database. Crit Care Med 2005; 33:1961-7. 10.1097/01. CCM.0000172279.66229.07 pmid: 16148466.

63 Liaño F, Gallego A, Pascual J, et al. Prognosis of acute tubular necrosis: an extended prospectively contrasted study. Nephron 1993; 63:21-31. 10.1159/000187139 pmid: 8446248.

64 Demirjian S, Chertow GM, Zhang JH, et al. VA/NIH Acute Renal Failure Trial Network. Model to predict mortality in critically ill adults with acute kidney injury. Clin J Am Soc Nephrol 2011; 6:2114-20. 10.2215/ CJN.02900311 pmid: 21896828.

65 da Hora Passos R, Ramos JG, Mendonça EJ, et al. A clinical score to predict mortality in septic acute kidney injury patients requiring continuous renal replacement therapy: the HELENICC score. BMC Anesthesiol 2017; 17:21. 10.1186/s12871-017-0312- 8 pmid: 28173756.

66 Le Gall JR, Lemeshow S, Saulnier F. A new Simplified Acute Physiology Score (SAPS II) based on a European/North American multicenter study. JAMA 1993; 270:2957-63. 10.1001/ jama.1993.03510240069035 pmid: 8254858.

67 Ohnuma T, Uchino S, Toki N, et al. JSEPTIC (Japanese Society for Physicians and Trainees in Intensive Care) Clinical Trial Group. External Validation for Acute Kidney Injury Severity Scores: A Multicenter Retrospective Study in 14 Japanese ICUs. Am J Nephrol 2015; 42:57-64. 10.1159/000439118 pmid: 26337793.

68 Basu RK, Wang Y, Wong HR, Chawla LS, Wheeler DS, Goldstein SL. Incorporation of biomarkers with the renal angina index for prediction of severe AKI in critically ill children. Clin J Am Soc Nephrol 2014; 9:654-62. 10.2215/CJN.09720913 pmid: 24677554.

69 Rizk DV, Meier D, Sandoval RM, et al. A Novel Method for Rapid Bedside Measurement of GFR. J Am Soc Nephrol 2018; 29:1609-13. 10.1681/ ASN.2018020160 pmid: 29748326.

70 Kim H, Hur M, Lee S, et al. GREAT Network. Proenkephalin, Neutrophil Gelatinase-Associated Lipocalin, and Estimated Glomerular Filtration Rates in Patients With Sepsis. Ann Lab Med 2017; 37:388-97. 10.3343/ alm.2017.37.5.388 pmid: 28643487.

71 Mårtensson J, Martling CR, Oldner A, Bell M. Impact of sepsis on levels of plasma cystatin C in AKI and non-AKI patients. Nephrol Dial Transplant 2012;27: 576-81. 10.1093/ndt/gfr358 pmid: 21765189.

72 Dai X, Zeng Z, Fu C, Zhang S, Cai Y, Chen Z. Diagnostic value of neutrophil gelatinase-associated lipocalin, cystatin C, and soluble triggering receptor expressed on myeloid cells-1 in critically ill patients with sepsis-associated acute kidney injury. Crit Care 2015; 19:223. 10.1186/ s13054-015-0941-6 pmid: 25944130.

73 Honore PM, Nguyen HB, Gong M, et al. Sapphire and Topaz Investigators. Urinary Tissue Inhibitor of Metalloproteinase-2 and Insulin-Like Growth Factor-Binding Protein 7 for Risk Stratification of Acute Kidney Injury in Patients With Sepsis. Crit Care Med 2016; 44:1851-60. 10.1097/ CCM.0000000000001827 pmid: 27355527.

74 Ko GJ, Grigoryev DN, Linfert D, et al. Transcriptional analysis of kidneys during repair from AKI reveals possible roles for NGAL and KIM-1 as biomarkers of AKI-to-CKD transition. Am J Physiol Renal Physiol 2010; 298:F1472-83. 10.1152/ ajprenal.00619.2009 pmid: 20181666.

75 McWilliam SJ, Antoine DJ, Jorgensen AL, Smyth RL, Pirmohamed M. Urinary Biomarkers of Aminoglycoside-Induced Nephrotoxicity in Cystic Fibrosis: Kidney Injury Molecule-1 and Neutrophil Gelatinase-Associated Lipocalin. Sci Rep 2018; 8:5094. 10.1038/s41598-018-23466- 4 pmid: 29572451.

76 de Geus HR, Betjes MG, Schaick Rv, Groeneveld JA. Plasma NGAL similarly predicts acute kidney injury in sepsis and nonsepsis. Biomark Med 2013; 7:415-21. 10.2217/bmm.13.5 pmid: 23734805.

77 Haase M, Devarajan P, Haase-Fielitz A, et al. The outcome of neutrophil gelatinase-associated lipocalin-positive subclinical acute kidney injury: a multicenter pooled analysis of prospective studies. J Am Coll Cardiol 2011;57:1752-61. 10.1016/j.jacc.2010.11.051 pmid: 21511111.

78 Nickolas TL, O’Rourke MJ, Yang J, et al. Sensitivity and specificity of a single emergency department measurement of urinary neutrophil gelatinase-associated lipocalin for diagnosing acute kidney injury. Ann Intern Med 2008; 148:810-9. 10.7326/0003-4819-148-11- 200806030-00003 pmid: 18519927.

79 Md Ralib A, Mat Nor MB, Pickering JW. Plasma Neutrophil Gelatinase- Associated Lipocalin diagnosed acute kidney injury in patients with systemic inflammatory disease and sepsis. Nephrology (Carlton) 2017; 22:412-9. 10.1111/nep.12796 pmid: 27062515.

80 de Geus HR, Fortrie G, Betjes MG, van Schaik RH, Groeneveld AB. Time of injury affects urinary biomarker predictive values for acute kidney injury in critically ill, non-septic patients. BMC Nephrol 2013; 14:273. 10.1186/1471-2369-14-273 pmid: 24321290.

81 Chen LX, Koyner JL. Biomarkers in Acute Kidney Injury. Crit Care Clin 2015;31: 633-48. 10.1016/j.ccc.2015.06.002 pmid: 26410134.

82 Hodgson LE, Sarnowski A, Roderick PJ, Dimitrov BD, Venn RM, Forni LG. Systematic review of prognostic prediction models for acute kidney injury (AKI) in general hospital populations. BMJ Open 2017; 7:e016591. 10.1136/bmjopen-2017-016591 pmid: 28963291.

83 Bhattacharjee P, Edelson DP, Churpek MM. Identifying Patients With Sepsis on the Hospital Wards. Chest 2017; 151:898-907. 10.1016/j. chest.2016.06.020 pmid: 27374948.

84 Koyner JL, Adhikari R, Edelson DP, Churpek MM. Development of a Multicenter Ward-Based AKI Prediction Model. Clin J Am Soc Nephrol 2016; 11:1935-43. 10.2215/CJN.00280116 pmid: 27633727.

85 Gómez H, Kellum JA. Sepsis-induced acute kidney injury. Curr Opin Crit Care 2016; 22:546-53. 10.1097/ MCC.0000000000000356 pmid: 27661757.

86 Keir I, Kellum JA. Acute kidney injury in severe sepsis: pathophysiology, diagnosis, and treatment recommendations. J Vet Emerg Crit Care (San Antonio) 2015; 25:200-9. 10.1111/vec.12297 pmid: 25845505.

87 Pool R, Gomez H, Kellum JA. Mechanisms of Organ Dysfunction in Sepsis. Crit Care Clin 2018; 34:63-80. 10.1016/j. ccc.2017.08.003 pmid: 29149942.

88 Fani F, Regolisti G, Delsante M, et al. Recent advances in the pathogenetic mechanisms of sepsis-associated acute kidney injury. J Nephrol 2018; 31:351-9. 10.1007/s40620-017-0452-4 pmid: 29273917.

89 Langenberg C, Gobe G, Hood S, May CN, Bellomo R. Renal histopathology during experimental septic acute kidney injury and recovery. Crit Care Med 2014; 42:e58-67. 10.1097/CCM.0b013e3182a639da pmid: 24126439.

90 Maiden MJ, Otto S, Brealey JK, et al. Structure and Function of the Kidney in Septic Shock. A Prospective Controlled Experimental Study. Am J Respir Crit Care Med 2016; 194:692-700. 10.1164/rccm.201511- 2285OC pmid: 26967568.

91 Nemzek JA, Hugunin KM, Opp MR. Modeling sepsis in the laboratory: merging sound science with animal well-being. Comp Med 2008; 58:120- 8.pmid:18524169.

92 Prowle JR, Ishikawa K, May CN, Bellomo R. Renal plasma flow and glomerular filtration rate during acute kidney injury in man. Ren Fail 2010; 32:349-55. 10.3109/08860221003611695 pmid: 20370451.

93 Redfors B, Bragadottir G, Sellgren J, Swärd K, Ricksten SE. Effects of norepinephrine on renal perfusion, filtration and oxygenation in vasodilatory shock and acute kidney injury. Intensive Care Med 2011; 37:60-7. 10.1007/s00134-010-2057-4 pmid: 20949349.

94 Prowle JR, Molan MP, Hornsey E, Bellomo R. Measurement of renal blood flow by phase-contrast magnetic resonance imaging during septic acute kidney injury: a pilot investigation. Crit Care Med 2012; 40:1768-76. 10.1097/CCM.0b013e318246bd85 pmid: 22487999.

95 National Institute of Diabetes and Digestive and Kidney Diseases. Kidney Precision Medicine Project. 2018. https://www.niddk.nih.gov/research-funding/research-programs/kidney-precision-medicine-project-kpmp.

96 Post EH, Kellum JA, Bellomo R, Vincent JL. Renal perfusion in sepsis: from macro- to microcirculation. Kidney Int 2017; 91:45-60. 10.1016/j. kint.2016.07.032 pmid: 27692561.

97 Chelazzi C, Villa G, Mancinelli P, De Gaudio AR, Adembri C. Glycocalyx and sepsis-induced alterations in vascular permeability. Crit Care 2015; 19:26. 10.1186/s13054-015-0741-z pmid: 25887223.

98 Tsukahara Y, Morisaki T, Kojima M, Uchiyama A, Tanaka M. iNOS expression by activated neutrophils from patients with sepsis. ANZ J Surg 2001; 71:15-20. 10.1046/j.1440- 1622.2001.02025.x pmid: 11167591.

99 Guerci P, Ergin B, Ince C. The macro- and microcirculation of the kidney. Best Pract Res Clin Anaesthesiol 2017; 31:315-29. 10.1016/j. bpa.2017.10.002 pmid:29248139.

100 Lankadeva YR, Kosaka J, Evans RG, Bailey SR, Bellomo R, May CN. Intrarenal and urinary oxygenation during norepinephrine resuscitation in ovine septic acute kidney injury. Kidney Int 2016; 90:100-8. 10.1016/j. kint.2016.02.017 pmid: 27165831.

101 Lankadeva YR, Kosaka J, Evans RG, Bellomo R, May CN. Urinary Oxygenation as a Surrogate Measure of Medullary Oxygenation During Angiotensin II Therapy in Septic Acute Kidney Injury. Crit Care Med 2018; 46:e41-8. 10.1097/CCM.0000000000002797 pmid: 29077618.

102 Schneider AG, Calzavacca P, Schelleman A, et al. Contrast-enhanced ultrasound evaluation of renal microcirculation in sheep. Intensive Care Med Exp 2014; 2:33. 10.1186/s40635-014-0033-y pmid: 26266930.

103 Tumlin JA, Murugan R, Deane AM, et al. Angiotensin II for the Treatment of High-Output Shock 3 (ATHOS-3) Investigators. Outcomes in Patients with Vasodilatory Shock and Renal Replacement Therapy Treated with Intravenous Angiotensin II. Crit Care Med 2018; 46:949-57. 10.1097/ CCM.0000000000003092 pmid: 29509568.

104 Rowan KM, Angus DC, Bailey M, et al. PRISM Investigators. Early, Goal- Directed Therapy for Septic Shock - A Patient-Level Meta-Analysis. N Engl J Med 2017; 376:2223-34. 10.1056/NEJMoa1701380 pmid: 28320242.

105 Rivers E, Nguyen B, Havstad S, et al. Early Goal-Directed Therapy Collaborative Group. Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med 2001; 345:1368-77. 10.1056/ NEJMoa010307 pmid:11794169.

106 Kellum JA, Pike F, Yealy DM, Huang DT, Shapiro NI, Angus DC. and the Protocol-based Care for Early Septic Shock Investigators (ProCESS) Investigators. Relationship Between Alternative Resuscitation Strategies, Host Response and Injury Biomarkers, and Outcome in Septic Shock: Analysis of the Protocol-Based Care for Early Septic Shock Study. Crit Care Med 2017; 45:438-45. 10.1097/ CCM.0000000000002206 pmid: 28079606.

107 Wiedemann HP, Wheeler AP, Bernard GR, et al. National Heart, Lung, and Blood Institute Acute Respiratory Distress Syndrome (ARDS) Clinical Trials Network. Comparison of two fluid-management strategies in acute lung injury. N Engl J Med 2006; 354:2564-75. 10.1056/ NEJMoa062200 pmid: 16714767.

108 Payen D, de Pont AC, Sakr Y, Spies C, Reinhart K, Vincent JL. Sepsis Occurrence in Acutely Ill Patients (SOAP) Investigators. A positive fluid balance is associated with a worse outcome in patients with acute renal failure. Crit Care 2008; 12:R74. 10.1186/cc6916 pmid:18533029.

109 Liu KD, Thompson BT, Ancukiewicz M, et al. National Institutes of Health National Heart, Lung, and Blood Institute Acute Respiratory Distress Syndrome Network. Acute kidney injury in patients with acute lung injury: impact of fluid accumulation on classification of acute kidney injury and associated outcomes. Crit Care Med 2011; 39:2665-71. 10.1097/ CCM.0b013e318228234b pmid:21785346.

110 Grams ME, Estrella MM, Coresh J, Brower RG, Liu KD. National Heart, Lung, and Blood Institute Acute Respiratory Distress Syndrome Network. Fluid balance, diuretic use, and mortality in acute kidney injury. Clin J Am Soc Nephrol 2011;6:966-73. 10.2215/CJN.08781010 pmid: 21393482.

111 Glassford NJ, Bellomo R. Does Fluid Type and Amount Affect Kidney Function in Critical Illness?Crit Care Clin 2018;34:279-98. 10.1016/j. ccc.2017.12.006 pmid: 29482907.

112 Perner A, Prowle J, Joannidis M, Young P, Hjortrup PB, Pettilä V. Fluid management in acute kidney injury. Intensive Care Med 2017; 43:807-15. 10.1007/s00134-017-4817-x pmid: 28470347.

113 Howell MD, Davis AM. Management of Sepsis and Septic Shock. JAMA 2017;317:847-8. 10.1001/jama.2017.0131 pmid: 28114603.

114 Bouchard J, Soroko SB, Chertow GM, et al. Program to Improve Care in Acute Renal Disease (PICARD) Study Group. Fluid accumulation, survival and recovery of kidney function in critically ill patients with acute kidney injury. Kidney Int 2009; 76:422-7. 10.1038/ki.2009.159 pmid: 19436332.

115 Brunkhorst FM, Engel C, Bloos F, et al. German Competence Network Sepsis (SepNet). Intensive insulin therapy and pentastarch resuscitation in severe sepsis. N Engl J Med 2008; 358:125-39. 10.1056/ NEJMoa070716 pmid: 18184958.

116 Perner A, Haase N, Guttormsen AB, et al. 6S Trial Group Scandinavian Critical Care Trials Group. Hydroxyethyl starch 130/0.42 versus Ringer’s acetate in severe sepsis. N Engl J Med 2012; 367:124-34. 10.1056/ NEJMoa1204242 pmid: 22738085.

117 Myburgh JA, Finfer S, Bellomo R, et al. CHEST Investigators Australian and New Zealand Intensive Care Society Clinical Trials Group. Hydroxyethyl starch or saline for fluid resuscitation in intensive care. N Engl J Med 2012; 367:1901- 11. 10.1056/NEJMoa1209759 pmid: 23075127.

118 Haase N, Wetterslev J, Winkel P, Perner A. Bleeding and risk of death with hydroxyethyl starch in severe sepsis: post hoc analyses of a randomized clinical trial. Intensive Care Med 2013; 39:2126-34. 10.1007/s00134-013- 3111-9 pmid: 24081433.

119 Zarychanski R, Abou-Setta AM, Turgeon AF, et al. Association of hydroxyethyl starch administration with mortality and acute kidney injury in critically ill patients requiring volume resuscitation: a systematic review and meta-analysis. JAMA 2013; 309:678-88. 10.1001/ jama.2013.430 pmid: 23423413.

120 Finfer S, McEvoy S, Bellomo R, McArthur C, Myburgh J, Norton R. SAFE Study Investigators. Impact of albumin compared to saline on organ function and mortality of patients with severe sepsis. Intensive Care Med 2011; 37:86-96. 10.1007/s00134-010-2039-6 pmid: 20924555.

121 Caironi P, Tognoni G, Masson S, et al. ALBIOS Study Investigators. Albumin replacement in patients with severe sepsis or septic shock. N Engl J Med 2014; 370:1412-21. 10.1056/NEJMoa1305727 pmid: 24635772.

122 Jiang L, Jiang S, Zhang M, Zheng Z, Ma Y. Albumin versus other fluids for fluid resuscitation in patients with sepsis: a meta-analysis. PLoS One 2014; 9:e114666. 10.1371/journal.pone.0114666 pmid: 25474401.

123 Xu JY, Chen QH, Xie JF, et al. Comparison of the effects of albumin and crystalloid on mortality in adult patients with severe sepsis and septic shock: a meta-analysis of randomized clinical trials. Crit Care 2014; 18:702. 10.1186/s13054-014-0702-y pmid: 25499187.

124 Raghunathan K, Bonavia A, Nathanson BH, et al. Association between Initial Fluid Choice and Subsequent In-hospital Mortality during the Resuscitation of Adults with Septic Shock. Anesthesiology 2015; 123:1385-93. 10.1097/ ALN.0000000000000861 pmid: 26414499.

125 Yunos NM, Bellomo R, Hegarty C, Story D, Ho L, Bailey M. Association between a chloride-liberal vs chloride-restrictive intravenous fluid administration strategy and kidney injury in critically ill adults. JAMA 2012; 308:1566-72. 10.1001/jama.2012.13356 pmid: 23073953.

126 Shaw AD, Bagshaw SM, Goldstein SL, et al. Major complications, mortality, and resource utilization after open abdominal surgery: 0.9% saline compared to Plasma-Lyte. Ann Surg 2012; 255:821-9. 10.1097/ SLA.0b013e31825074f5 pmid: 22470070.

127 Young P, Bailey M, Beasley R, et al. SPLIT Investigators ANZICS CTG. Effect of a Buffered Crystalloid Solution vs Saline on Acute Kidney Injury Among Patients in the Intensive Care Unit: The SPLIT Randomized Clinical Trial. JAMA 2015; 314:1701-10. 10.1001/jama.2015.12334 pmid: 26444692.

128 Raghunathan K, Shaw A, Nathanson B, et al. Association between the choice of IV crystalloid and in-hospital mortality among critically ill adults with sepsis*. Crit Care Med 2014; 42:1585-91. 10.1097/ CCM.0000000000000305 pmid: 24674927.

129 Self WH, Semler MW, Wanderer JP, et al. SALT-ED Investigators. Balanced Crystalloids versus Saline in Noncritically Ill Adults. N Engl J Med 2018; 378:819-28. 10.1056/NEJMoa1711586 pmid: 29485926.

130 Semler MW, Self WH, Wanderer JP, et al. SMART Investigators and the Pragmatic Critical Care Research Group. Balanced Crystalloids versus Saline in Critically Ill Adults. N Engl J Med 2018; 378:829-39. 10.1056/ NEJMoa1711584 pmid: 29485925.

131 Gordon AC, Mason AJ, Thirunavukkarasu N, et al. VANISH Investigators. Effect of Early Vasopressin vs Norepinephrine on Kidney Failure in Patients With Septic Shock: The VANISH Randomized Clinical Trial. JAMA 2016; 316:509-18. 10.1001/jama.2016.10485 pmid: 27483065.

132 Kellum JA, M Decker J. Use of dopamine in acute renal failure: a meta-analysis. Crit Care Med 2001; 29:1526-31. 10.1097/00003246- 200108000-00005 pmid: 11505120.

133 Vail E, Gershengorn HB, Hua M, Walkey AJ, Rubenfeld G, Wunsch H. Association Between US Norepinephrine Shortage and Mortality Among Patients With Septic Shock. JAMA 2017; 317:1433-42. 10.1001/ jama.2017.2841 pmid: 28322415.

134 Gordon AC, Perkins GD, Singer M, et al. Levosimendan for the Prevention of Acute Organ Dysfunction in Sepsis. N Engl J Med 2016; 375:1638-48. 10.1056/NEJMoa1609409 pmid: 27705084.

135 Khanna A, English SW, Wang XS, et al. ATHOS-3 Investigators. Angiotensin II for the Treatment of Vasodilatory Shock. N Engl J Med 2017; 377:419-30. 10.1056/NEJMoa1704154 pmid: 28528561.

136 De Backer D, Biston P, Devriendt J, et al. SOAP II Investigators. Comparison of dopamine and norepinephrine in the treatment of shock. N Engl J Med 2010; 362:779-89. 10.1056/NEJMoa0907118 pmid: 20200382.

137 Lauzier F, Lévy B, Lamarre P, Lesur O. Vasopressin or norepinephrine in early hyperdynamic septic shock: a randomized clinical trial. Intensive Care Med 2006; 32:1782-9. 10.1007/s00134-006-0378-0 pmid:17019548.

138 Morelli A, Ertmer C, Rehberg S, et al. Phenylephrine versus norepinephrine for initial hemodynamic support of patients with septic shock: a randomized, controlled trial. Crit Care 2008; 12:R143. 10.1186/ cc7121 pmid: 19017409.

139 Myburgh JA, Higgins A, Jovanovska A, Lipman J, Ramakrishnan N, Santamaria J. CAT Study investigators. A comparison of epinephrine and norepinephrine in critically ill patients. Intensive Care Med 2008; 34:2226- 34. 10.1007/s00134-008-1219-0 pmid: 18654759.

140 Hallengren M, Åstrand P, Eksborg S, Barle H, Frostell C. Septic shock and the use of norepinephrine in an intermediate care unit: Mortality and adverse events. PLoS One 2017; 12:e0183073. 10.1371/journal. pone.0183073 pmid: 28837628.

141 Russell JA, Walley KR, Singer J, et al. VASST Investigators. Vasopressin versus norepinephrine infusion in patients with septic shock. N Engl J Med 2008; 358:877-87. 10.1056/NEJMoa067373 pmid: 18305265.

142 Morelli A, De Castro S, Teboul JL, et al. Effects of levosimendan on systemic and regional hemodynamics in septic myocardial depression. Intensive Care Med 2005; 31:638-44. 10.1007/s00134-005- 2619-z pmid: 15812624.

143 Asfar P, Meziani F, Hamel JF, et al. SEPSISPAM Investigators. High versus low blood-pressure target in patients with septic shock. N Engl J Med 2014; 370:1583-93. 10.1056/NEJMoa1312173 pmid: 24635770.

144 Drury DR, Henry JP, Goodman J. THE EFFECTS OF CONTINUOUS PRESSURE BREATHING ON KIDNEY FUNCTION. J Clin Invest 1947; 26:945-51. 10.1172/JCI101889 pmid: 16695498.

145 van den Akker JP, Egal M, Groeneveld AB. Invasive mechanical ventilation as a risk factor for acute kidney injury in the critically ill: a systematic review and meta-analysis. Crit Care 2013; 17:R98. 10.1186/ cc12743 pmid: 23710662.

146 Broden CC. Acute renal failure and mechanical ventilation: reality or myth?Crit Care Nurse 2009;29:62-75, quiz 76. 10.4037/ ccn2009267 pmid: 19339448.

147 Koyner JL, Murray PT. Mechanical ventilation and lung-kidney interactions. Clin J Am Soc Nephrol 2008; 3:562-70. 10.2215/ CJN.03090707 pmid: 18256378.

148 Kuiper JW, Groeneveld AB, Slutsky AS, Plötz FB. Mechanical ventilation and acute renal failure. Crit Care Med 2005; 33:1408-15. 10.1097/01. CCM.0000165808.30416.EF pmid: 15942363.

149 Daher EF, Marques CN, Lima RS, et al. Acute kidney injury in an infectious disease intensive care unit - an assessment of prognostic factors. Swiss Med Wkly 2008; 138:128-33.pmid:18330732.

150 Brower RG, Matthay MA, Morris A, Schoenfeld D, Thompson BT, Wheeler A. 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. 10.1056/ NEJM200005043421801 pmid: 10793162.

151 Cavalcanti AB, Suzumura EA, Laranjeira LN, et al. Writing Group for the Alveolar Recruitment for Acute Respiratory Distress Syndrome Trial (ART) Investigators. Effect of Lung Recruitment and Titrated Positive End-Expiratory Pressure (PEEP) vs Low PEEP on Mortality in Patients With Acute Respiratory Distress Syndrome: A Randomized Clinical Trial. JAMA 2017; 318:1335-45. 10.1001/jama.2017.14171 pmid: 28973363.

152 Mercat A, Richard JC, Vielle B, et al. Expiratory Pressure (Express) Study Group. Positive end-expiratory pressure setting in adults with acute lung injury and acute respiratory distress syndrome: a randomized controlled trial. JAMA 2008;299:646-55. 10.1001/ jama.299.6.646 pmid: 18270353.

153 Frat JP, Thille AW, Mercat A, et al. FLORALI Study Group REVA Network. High-flow oxygen through nasal cannula in acute hypoxemic respiratory failure. N Engl J Med 2015; 372:2185-96. 10.1056/ NEJMoa1503326 pmid: 25981908.

154 Patel BK, Wolfe KS, Pohlman AS, Hall JB, Kress JP. Effect of Noninvasive Ventilation Delivered by Helmet vs Face Mask on the Rate of Endotracheal Intubation in Patients With Acute Respiratory Distress Syndrome: A Randomized Clinical Trial. JAMA 2016; 315:2435-41. 10.1001/ jama.2016.6338 pmid: 27179847.

155 Mehta RL, Pascual MT, Soroko S, Chertow GM. PICARD Study Group. Diuretics, mortality, and nonrecovery of renal function in acute renal failure. JAMA 2002; 288:2547-53. 10.1001/jama.288.20.2547 pmid: 12444861.

156 Uchino S, Doig GS, Bellomo R, et al. Beginning and Ending Supportive Therapy for the Kidney (B.E.S.T. Kidney) Investigators. Diuretics and mortality in acute renal failure. Crit Care Med 2004; 32:1669-77. 10.1097/01. CCM.0000132892.51063.2F pmid: 15286542.

157 Ho KM, Sheridan DJ. Meta-analysis of frusemide to prevent or treat acute renal failure. BMJ 2006; 333:420. 10.1136/ bmj.38902.605347.7C pmid: 16861256.

158 Peters E, Heuberger JAAC, Tiessen R, et al. Pharmacokinetic Modeling and Dose Selection in a Randomized, Double-Blind, Placebo-Controlled Trial of a Human Recombinant Alkaline Phosphatase in Healthy Volunteers. Clin Pharmacokinet 2016; 55:1227-37. 10.1007/s40262-016- 0399-y pmid: 27147514.

159 Peters E, Mehta RL, Murray PT, et al. Study protocol for a multicentre randomised controlled trial: Safety, Tolerability, efficacy and quality of life Of a human recombinant alkaline Phosphatase in patients with sepsis-associated Acute Kidney Injury (STOP-AKI). BMJ Open 2016; 6:e012371. 10.1136/bmjopen-2016-012371 pmid: 27678541.

160 Koyama I, Matsunaga T, Harada T, Hokari S, Komoda T. Alkaline phosphatases reduce toxicity of lipopolysaccharides in vivo and in vitro through dephosphorylation. Clin Biochem 2002; 35:455-61. 10.1016/ S0009-9120(02)00330-2 pmid: 12413606.

161 Pickkers P, Mehta RL, Murray PT, et al. STOP-AKI Investigators. Effect of Human Recombinant Alkaline Phosphatase on 7-Day Creatinine Clearance in Patients With Sepsis-Associated Acute Kidney Injury: A Randomized Clinical Trial. JAMA 2018; 320:1998-2009. 10.1001/ jama.2018.14283 pmid: 30357272.

162 DiRocco DP, Bisi J, Roberts P, et al. CDK4/6 inhibition induces epithelial cell cycle arrest and ameliorates acute kidney injury. Am J Physiol Renal Physiol 2014; 306:F379-88. 10.1152/ajprenal.00475.2013 pmid: 24338822.

163 Cantaluppi V, Medica D, Quercia AD, et al. Perfluorocarbon solutions limit tubular epithelial cell injury and promote CD133+ kidney progenitor differentiation: potential use in renal assist devices for sepsis-associated acute kidney injury and multiple organ failure. Nephrol Dial Transplant 2018; 33:1110-21. 10.1093/ndt/gfx328 pmid: 29267971.

164 Yu G, Liu Q, Dong X, et al. Inhibition of inflammation using diacerein markedly improved renal function in endotoxemic acute kidney injured mice. Cell Mol Biol Lett 2018; 23:38. 10.1186/s11658-018-0107-z pmid: 30140293.

165 Luo CJ, Luo F, Zhang L, et al. Knockout of interleukin-17A protects against sepsis-associated acute kidney injury. Ann Intensive Care 2016; 6:56. 10.1186/s13613-016-0157-1 pmid: 27334720.

166 Murugan R, Weissfeld L, Yende S, Singbartl K, Angus DC, Kellum JA. Genetic and Inflammatory Markers of Sepsis (GenIMS) Investigators. Association of statin use with risk and outcome of acute kidney injury in community-acquired pneumonia. Clin J Am Soc Nephrol 2012; 7:895-905. 10.2215/ CJN.07100711 pmid: 22461537.

167 Deshpande A, Pasupuleti V, Rothberg MB. Statin therapy and mortality from sepsis: a meta-analysis of randomized trials. Am J Med 2015; 128:410-7.e1. 10.1016/j.amjmed.2014.10.057 pmid: 25526798.

168 Ergin B, Guerci P, Zafrani L, et al. Effects of N-acetylcysteine (NAC) supplementation in resuscitation fluids on renal microcirculatory oxygenation, inflammation, and function in a rat model of endotoxemia. Intensive Care Med Exp 2016; 4:29. 10.1186/s40635-016-0106- 1 pmid: 27671340.

169 Campos R, Shimizu MH, Volpini RA, et al. N-acetylcysteine prevents pulmonary edema and acute kidney injury in rats with sepsis submitted to mechanical ventilation. Am J Physiol Lung Cell Mol Physiol 2012; 302:L640- 50. 10.1152/ajplung.00097.2011 pmid: 22268121.

170 Weisbord SD, Gallagher M, Jneid H, et al. PRESERVE Trial Group. Outcomes after Angiography with Sodium Bicarbonate and Acetylcysteine. N Engl J Med 2018; 378:603-14. 10.1056/NEJMoa1710933 pmid: 29130810.

171 Komisarof JA, Gilkey GM, Peters DM, Koudelka CW, Meyer MM, Smith SM. N-acetylcysteine for patients with prolonged hypotension as prophylaxis for acute renal failure (NEPHRON). Crit Care Med 2007; 35:435-41. 10.1097/01.CCM.0000253816.83011.DB pmid: 17205018.

172 van den Berghe G, Wouters P, Weekers F, et al. Intensive insulin therapy in critically ill patients. N Engl J Med 2001; 345:1359-67. 10.1056/ NEJMoa011300 pmid: 11794168.

173 Finfer S, Chittock DR, Su SY, et al. NICE-SUGAR Study Investigators. Intensive versus conventional glucose control in critically ill patients. N Engl J Med 2009; 360:1283-97. 10.1056/NEJMoa0810625 pmid: 19318384.

174 Corwin HL, Gettinger A, Pearl RG, et al. EPO Critical Care Trials Group. Efficacy of recombinant human erythropoietin in critically ill patients: a randomized controlled trial. JAMA 2002; 288:2827-35. 10.1001/ jama.288.22.2827 pmid: 12472324.

175 Endre ZH, Walker RJ, Pickering JW, et al. Early intervention with erythropoietin does not affect the outcome of acute kidney injury (the EARLYARF trial). Kidney Int 2010;77:1020-30. 10.1038/ ki.2010.25 pmid: 20164823.

176 Annane D, Renault A, Brun-Buisson C, et al. CRICS-TRIGGERSEP Network. Hydrocortisone plus Fludrocortisone for Adults with Septic Shock. N Engl J Med 2018; 378:809-18. 10.1056/NEJMoa1705716 pmid: 29490185.

177 Venkatesh B, Finfer S, Cohen J, et al. ADRENAL Trial Investigators and the Australian–New Zealand Intensive Care Society Clinical Trials Group. Adjunctive Glucocorticoid Therapy in Patients with Septic Shock. N Engl J Med 2018; 378:797-808. 10.1056/NEJMoa1705835 pmid: 29347874.

178 Pickkers P, Heemskerk S, Schouten J, et al. Alkaline phosphatase for treatment of sepsis-induced acute kidney injury: a prospective randomized double-blind placebo-controlled trial. Crit Care 2012; 16:R14. 10.1186/ cc11159 pmid: 22269279.

179 Moskowitz A, Andersen LW, Cocchi MN, Karlsson M, Patel PV, Donnino MW. Thiamine as a Renal Protective Agent in Septic Shock. A Secondary Analysis of a Randomized, Double-Blind, Placebo-controlled Trial. Ann Am Thorac Soc 2017; 14:737-41. 10.1513/AnnalsATS.201608-656BC pmid: 28207287.

180 ClinicalTrials.gov. Phase 2 Study of reltecimod vs placebo in patients with sepsis-associated acute kidney injury. 2018. https://clinicaltrials.gov/ct2/ show/NCT03403751.

181 ClinicalTrials.gov. Impact of CVVHD with adsorption capacity membranes in septic acute kidney injury. 2018. https://clinicaltrials.gov/ct2/show/ NCT01790620.

182 ClinicalTrials.gov. The effect of fluid resuscitation with 0.9% sodium chloride versus balanced crystalloid solution on renal function of sepsis patients. 2018. https://clinicaltrials.gov/ct2/show/NCT03277677.

183 ClinicalTrials.gov. L-carnitine as an adjunct treatment for septic shock patients with acute kidney injury (CarniSave). 2018. https://clinicaltrials. gov/ct2/show/NCT02664753.

184 ClinicalTrials.gov. Impact of pediatric acute renal injury in severe sepsis in young adults (IMPRESS-YA). 2018. https://clinicaltrials.gov/ct2/show/ NCT02599844.

185 Gaudry S, Ricard JD, Leclaire C, et al. Acute kidney injury in critical care: experience of a conservative strategy. J Crit Care 2014; 29:1022-7. 10.1016/j.jcrc.2014.07.014 pmid:25123792.

186 Zarbock A, Kellum JA, Schmidt C, et al. Effect of Early vs Delayed Initiation of Renal Replacement Therapy on Mortality in Critically Ill Patients With Acute Kidney Injury: The ELAIN Randomized Clinical Trial. JAMA 2016; 315:2190-9. 10.1001/jama.2016.5828 pmid: 27209269.

187 Palevsky PM, Zhang JH, O’Connor TZ, et al. VA/NIH Acute Renal Failure Trial Network. Intensity of renal support in critically ill patients with acute kidney injury. N Engl J Med 2008; 359:7-20. 10.1056/ NEJMoa0802639 pmid:18492867.

188 Bellomo R, Cass A, Cole L, et al. RENAL Replacement Therapy Study Investigators. Intensity of continuous renal-replacement therapy in critically ill patients. N Engl J Med 2009; 361:1627-38. 10.1056/ NEJMoa0902413 pmid:19846848.

189 Wald R, Friedrich JO, Bagshaw SM, et al. Optimal Mode of clearance in critically ill patients with Acute Kidney Injury (OMAKI)--a pilot randomized controlled trial of hemofiltration versus hemodialysis: a Canadian Critical Care Trials Group project. Crit Care 2012; 16:R205. 10.1186/ cc11835 pmid: 23095370.

190 Barbar SD, Clere-Jehl R, Bourredjem A, et al. IDEAL-ICU Trial Investigators and the CRICS TRIGGERSEP Network. Timing of Renal-Replacement Therapy in Patients with Acute Kidney Injury and Sepsis. N Engl J Med 2018; 379:1431- 42. 10.1056/NEJMoa1803213 pmid: 30304656.

191 Payen D, Mateo J, Cavaillon JM, Fraisse F, Floriot C, Vicaut E. Hemofiltration and Sepsis Group of the Collège National de Réanimation et de Médecine d’Urgence des Hôpitaux extra-Universitaires. Impact of continuous venovenous hemofiltration on organ failure during the early phase of severe sepsis: a randomized controlled trial. Crit Care Med 2009; 37:803-10. 10.1097/CCM.0b013e3181962316 pmid: 19237881.

192 Gaudry S, Hajage D, Schortgen F, et al. AKIKI Study Group. Initiation Strategies for Renal-Replacement Therapy in the Intensive Care Unit. N Engl J Med 2016;375:122-33. 10.1056/NEJMoa1603017 pmid: 27181456.

193 Zhang P, Yang Y, Lv R, Zhang Y, Xie W, Chen J. Effect of the intensity of continuous renal replacement therapy in patients with sepsis and acute kidney injury: a single-center randomized clinical trial. Nephrol Dial Transplant 2012;27:967-73. 10.1093/ndt/gfr486 pmid: 21891773.

194 Joannes-Boyau O, Honoré PM, Perez P, et al. High-volume versus standard-volume haemofiltration for septic shock patients with acute kidney injury (IVOIRE study): a multicentre randomized controlled trial. Intensive Care Med 2013;39: 1535-46. 10.1007/s00134-013- 2967-z pmid: 23740278.

195 Park JT, Lee H, Kee YK, et al. HICORES Investigators. High-Dose Versus Conventional-Dose Continuous Venovenous Hemodiafiltration and Patient and Kidney Survival and Cytokine Removal in Sepsis-Associated Acute Kidney Injury: A Randomized Controlled Trial. Am J Kidney Dis 2016; 68:599- 608. 10.1053/j.ajkd.2016.02.049 pmid: 27084247.

196 Chung KK, Coates EC, Smith DJ Jr, et al. Randomized controlled Evaluation of high-volume hemofiltration in adult burn patients with Septic shoCk and acUte kidnEy injury (RESCUE) Investigators. High-volume hemofiltration in adult burn patients with septic shock and acute kidney injury: a multicenter randomized controlled trial. Crit Care 2017; 21:289. 10.1186/s13054- 017-1878-8 pmid: 29178943.

197 Gaudry S, Hajage D, Schortgen F, et al. Timing of Renal Support and Outcome of Septic Shock and Acute Respiratory Distress Syndrome. A Post Hoc Analysis of the AKIKI Randomized Clinical Trial. Am J Respir Crit Care Med 2018;198: 58-66. 10.1164/rccm.201706-1255OC pmid: 29351007.

198 Smith OM, Wald R, Adhikari NK, Pope K, Weir MA, Bagshaw SM. Canadian Critical Care Trials Group. Standard versus accelerated initiation of renal replacement therapy in acute kidney injury (STARRT-AKI): study protocol for a randomized controlled trial. Trials 2013; 14:320. 10.1186/1745-6215-14- 320 pmid:24093950.

199 Schefold JC, von Haehling S, Pschowski R, et al. The effect of continuous versus intermittent renal replacement therapy on the outcome of critically ill patients with acute renal failure (CONVINT): a prospective randomized controlled trial. Crit Care 2014; 18:R11. 10.1186/ cc13188 pmid: 24405734.

200 Vinsonneau C, Camus C, Combes A, et al. Hemodiafe Study Group. Continuous venovenous haemodiafiltration versus intermittent haemodialysis for acute renal failure in patients with multiple-organ dysfunction syndrome: a multicentre randomised trial. Lancet 2006; 368:379-85. 10.1016/S0140-6736(06)69111- 3 pmid: 16876666.

201 Bagshaw SM, Berthiaume LR, Delaney A, Bellomo R. Continuous versus intermittent renal replacement therapy for critically ill patients with acute kidney injury: a meta-analysis. Crit Care Med 2008; 36:610-7. 10.1097/01. CCM.0B013E3181611F552 pmid: 18216610.

202 Zhou F, Peng Z, Murugan R, Kellum JA. Blood purification and mortality in sepsis: a meta-analysis of randomized trials. Crit Care Med 2013; 41:2209- 20. 10.1097/CCM.0b013e31828cf412 pmid: 23860248.

203 Cruz DN, Antonelli M, Fumagalli R, et al. Early use of polymyxin B hemoperfusion in abdominal septic shock: the EUPHAS randomized controlled trial. JAMA 2009; 301:2445-52. 10.1001/ jama.2009.856 pmid: 19531784.

204 Dellinger RP, Bagshaw SM, Antonelli M, et al. EUPHRATES Trial Investigators. Effect of Targeted Polymyxin B Hemoperfusion on 28-Day Mortality in Patients With Septic Shock and Elevated Endotoxin Level: The EUPHRATES Randomized Clinical Trial. JAMA 2018; 320:1455-63. 10.1001/ jama.2018.14618 pmid: 30304428.

205 Forni LG, Darmon M, Ostermann M, et al. Renal recovery after acute kidney injury. Intensive Care Med 2017; 43:855-66. 10.1007/s00134-017- 4809-x pmid: 28466146.

206 Patel SS, Palant CE, Mahajan V, Chawla LS. Sequelae of AKI. Best Pract Res Clin Anaesthesiol 2017; 31:415-25. 10.1016/j. bpa.2017.08.004 pmid:29248147.

207 Cerdá J, Lameire N, Eggers P, et al. Epidemiology of acute kidney injury. Clin J Am Soc Nephrol 2008; 3:881-6. 10.2215/ CJN.04961107 pmid: 18216347.

208 Kellum JA, Sileanu FE, Bihorac A, Hoste EA, Chawla LS. Recovery after Acute Kidney Injury. Am J Respir Crit Care Med 2017; 195:784-91. 10.1164/ rccm.201604-0799OC pmid:27635668.

209 Venot M, Weis L, Clec’h C, et al. Acute Kidney Injury in Severe Sepsis and Septic Shock in Patients with and without Diabetes Mellitus: A Multicenter Study. PLoS One 2015; 10:e0127411. 10.1371/journal. pone. 0127411 pmid: 26020231.

210 Grams ME, Sang Y, Coresh J, et al. Acute Kidney Injury After Major Surgery: A Retrospective Analysis of Veterans Health Administration Data. Am J Kidney Dis 2016; 67:872-80. 10.1053/j.ajkd.2015.07.022 pmid: 26337133.

211 Sawhney S, Marks A, Fluck N, McLernon DJ, Prescott GJ, Black C. Acute kidney injury as an independent risk factor for unplanned 90-day hospital readmissions. BMC Nephrol 2017; 18:9. 10.1186/s12882-016-0430- 4 pmid: 28061831.

212 Brown JR, Hisey WM, Marshall EJ, et al. Acute Kidney Injury Severity and Long- Term Readmission and Mortality After Cardiac Surgery. Ann Thorac Surg 2016; 102:1482-9. 10.1016/j.athoracsur.2016.04.020 pmid: 27319985.

213 Prescott HC, Langa KM, Iwashyna TJ. Readmission diagnoses after hospitalization for severe sepsis and other acute medical conditions. JAMA 2015;313:1055-7. 10.1001/jama.2015.1410 pmid: 25756444.

214 Hsu CY. Yes, AKI truly leads to CKD. J Am Soc Nephrol 2012; 23:967-9. 10.1681/ASN.2012030222 pmid: 22499588.

215 Rifkin DE, Coca SG, Kalantar-Zadeh K. Does AKI truly lead to CKD?J Am Soc Nephrol 2012;23:979-84. 10.1681/ASN.2011121185 pmid: 22460531.

216 Christiansen S, Christensen S, Pedersen L, et al. Timing of renal replacement therapy and long-term risk of chronic kidney disease and death in intensive care patients with acute kidney injury. Crit Care 2017; 21:326. 10.1186/ s13054-017-1903-y pmid: 29282093.

217 Sawhney S, Marks A, Fluck N, et al. Post-discharge kidney function is associated with subsequent ten-year renal progression risk among survivors of acute kidney injury. Kidney Int 2017; 92:440-52. 10.1016/j. kint.2017.02.019 pmid: 28416224.

218 Mehta S, Chauhan K, Patel A, et al. The prognostic importance of duration of AKI: a systematic review and meta-analysis. BMC Nephrol 2018; 19:91. 10.1186/s12882-018-0876-7 pmid: 29673338.

219 Go AS, Parikh CR, Ikizler TA, et al. Assessment Serial Evaluation, and Subsequent Sequelae of Acute Kidney Injury Study Investigators. The assessment, serial evaluation, and subsequent sequelae of acute kidney injury (ASSESS-AKI) study: design and methods. BMC Nephrol 2010; 11:22. 10.1186/1471-2369-11-22 pmid: 20799966.

220 Husain-Syed F, Ferrari F, Sharma A, et al. Preoperative Renal Functional Reserve Predicts Risk of Acute Kidney Injury After Cardiac Operation. Ann Thorac Surg 2018; 105:1094-101. 10.1016/ j.athoracsur.2017.12.034 pmid: 29382510.

221 National Institute for Health and Care Excellence. Acute kidney injury: prevention, detection and management up to the point of renal replacement therapy. 2013. https://www.nice.org.uk/guidance/cg169.

222 Brochard L, Abroug F, Brenner M, et al. ATS/ERS/ESICM/SCCM/SRLF Ad Hoc Committee on Acute Renal Failure. An Official ATS/ERS/ESICM/SCCM/SRLF Statement: Prevention and Management of Acute Renal Failure in the ICU Patient: an international consensus conference in intensive care medicine. Am J Respir Crit Care Med 2010; 181:1128-55. 10.1164/rccm.200711- 1664ST pmid: 20460549.



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