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AKI in early sepsis is a continuum from transient AKI without tubular damage over transient AKI with minor tubular damage to intrinsic AKI with severe tubular damage

  • Nephrology – Original Paper
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Abstract

Purpose

The pathophysiology of septic acute kidney injury (AKI) is incompletely understood, and there is controversy on the role of renal hypoperfusion in early sepsis. We hypothesized that renal hypoperfusion plays a role in early sepsis and that there is a continuum between transient AKI without tubular damage, transient AKI with minor tubular damage, and intrinsic AKI.

Methods

A total of 107 consecutive patients with sepsis were included. Fractional excretion of sodium (FENa), urinary, and serum neutrophil gelatinase-associated lipocalin were measured at admission (T0) and 4 h (T4) and 24 h later (T24). Patients were classified according to FENa quartiles (FENaQ). Transient and intrinsic AKI were respectively defined as AKI that did or did not recover to no AKI in the following 5 days.

Results

A total of 57 developed transient AKI, 22 developed intrinsic AKI, and 28 did not have AKI. Of the ten patients with transient AKI classified in the two lowest FENa quartiles (FENa < 0.36 %) and without signs of local tubular damage, seven still did not show signs of tubular damage 24 h later. Also, 50 % of patients with intrinsic AKI classified in the same FENaQ did not show signs of local tubular damage at admission but did so 24 h later.

Conclusions

There is a continuum between transient AKI without tubular damage, transient AKI with minor tubular damage, and intrinsic AKI in sepsis. Renal hypoperfusion seems to be the instigator for the development of AKI in the majority of patients with early sepsis. Other mechanisms in some patients cannot be excluded.

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References

  1. 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, Beginning and Ending Supportive Therapy for the Kidney (BEST Kidney) Investigators (2007) Septic acute kidney injury in critically ill patients: clinical characteristics and outcomes. Clin J Am Soc Nephrol 2(3):431–439

    Article  PubMed  Google Scholar 

  2. Wan L, Bagshaw SM, Langenberg C, Saotome T, May C, Bellomo R (2008) Pathophysiology of septic acute kidney injury: what do we really know? Crit Care Med 36(4 Suppl):S198–S203

    Article  PubMed  Google Scholar 

  3. Matejovic M, Radermacher P, Joannidis M (2007) Acute kidney injury in sepsis: is renal blood flow more than just an innocent bystander? Intensive Care Med 33(9):1498–1500

    Article  PubMed  Google Scholar 

  4. Molitoris BA (2005) Renal blood flow in sepsis: a complex issue. Crit Care 9(4):327-328

    Article  PubMed  PubMed Central  Google Scholar 

  5. Wang Z, Holthoff JH, Seely KA, Pathak E, Spencer HJ III, Gokden N, Mayeux PR (2012) Development of oxidative stress in the peritubular capillary microenvironment mediates sepsis-induced renal microcirculatory failure and acute kidney injury. Am J Pathol 180(2):505–516

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  6. Zarjou A, Agarwal A (2011) Sepsis and acute kidney injury. [Review]. J Am Soc Nephrol 22(6):999–1006

    Article  PubMed  Google Scholar 

  7. Haase M, Kellum JA, Ronco C (2012) Subclinical AKI–an emerging syndrome with important consequences. Nat Rev Nephrol 8(12):735–739

    Article  PubMed  CAS  Google Scholar 

  8. (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 (6):864–874

  9. Macedo E, Malhotra R, Claure-Del GR, Fedullo P, Mehta RL (2011) Defining urine output criterion for acute kidney injury in critically ill patients. Nephrol Dial Transplant 26(2):509–515

    Article  PubMed  PubMed Central  Google Scholar 

  10. 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(4):R204–R212

    Article  PubMed  PubMed Central  Google Scholar 

  11. Axelsson L, Bergenfeldt M, Ohlsson K (1995) Studies of the release and turnover of a human neutrophil lipocalin. Scand J Clin Lab Invest 55(7):577–588

    Article  PubMed  CAS  Google Scholar 

  12. Mori K, Lee HT, Rapoport D, Drexler IR, Foster K, Yang J, Schmidt-Ott KM, Chen X, Li JY, Weiss S, Mishra J, Cheema FH, Markowitz G, Suganami T, Sawai K, Mukoyama M, Kunis C, D’Agati V, Devarajan P, Barasch J (2005) Endocytic delivery of lipocalin-siderophore-iron complex rescues the kidney from ischemia-reperfusion injury. J Clin Invest 115(3):610–621

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  13. Vanmassenhove J, Glorieux G, Hoste E, Dhondt A, Vanholder R, Van BW (2013) Urinary output and fractional excretion of sodium and urea as indicators of transient versus intrinsic acute kidney injury during early sepsis. Crit Care 17(5):R234

    Article  PubMed  PubMed Central  Google Scholar 

  14. Bellomo R, Bagshaw S, Langenberg C, Ronco C (2007) Pre-renal azotemia: a flawed paradigm in critically ill septic patients? Contrib Nephrol 156:1–9

    Article  PubMed  Google Scholar 

  15. Goldstein SL, Chawla LS (2010) Renal angina. Clin J Am Soc Nephrol 5(5):943–949

    Article  PubMed  Google Scholar 

  16. Doi K, Katagiri D, Negishi K, Hasegawa S, Hamasaki Y, Fujita T, Matsubara T, Ishii T, Yahagi N, Sugaya T, Noiri E (2012) Mild elevation of urinary biomarkers in prerenal acute kidney injury. Kidney Int 82(10):1114–1120

    Article  PubMed  CAS  Google Scholar 

  17. Nejat M, Pickering JW, Devarajan P, Bonventre JV, Edelstein CL, Walker RJ, Endre ZH (2012) Some biomarkers of acute kidney injury are increased in pre-renal acute injury. Kidney Int 81(12):1254–1262

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  18. Paragas N, Qiu A, Zhang Q, Samstein B, Deng SX, Schmidt-Ott KM, Viltard M, Yu W, Forster CS, Gong G, Liu Y, Kulkarni R, Mori K, Kalandadze A, Ratner AJ, Devarajan P, Landry DW, D’Agati V, Lin CS, Barasch J (2011) The Ngal reporter mouse detects the response of the kidney to injury in real time. Nat Med 17(2):216–222

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  19. Haase M, Bellomo R, Devarajan P, Schlattmann P, Haase-Fielitz A (2009) Accuracy of neutrophil gelatinase-associated lipocalin (NGAL) in diagnosis and prognosis in acute kidney injury: a systematic review and meta-analysis. Am J Kidney Dis 54(6):1012–1024

    Article  PubMed  CAS  Google Scholar 

  20. Haase M, Devarajan P, Haase-Fielitz A, Bellomo R, Cruz DN, Wagener G, Krawczeski CD, Koyner JL, Murray P, Zappitelli M, Goldstein SL, Makris K, Ronco C, Martensson J, Martling CR, Venge P, Siew E, Ware LB, Ikizler TA, Mertens PR (2011) The outcome of neutrophil gelatinase-associated lipocalin-positive subclinical acute kidney injury: a multicenter pooled analysis of prospective studies. J Am Coll Cardiol 57(17):1752–1761

    Article  PubMed  CAS  Google Scholar 

  21. Giasson J, Li GH, Chen Y (2011) Neutrophil gelatinase-associated lipocalin (NGAL) as a new biomarker for non–acute kidney injury (AKI) diseases. Inflamm Allergy Drug Targets 10(4):272–282

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

JV was supported by a Grant from the Klinisch OnderzoeksFonds (KOF) of the Ghent University Hospital. The authors thank A De Jonghe, MA Waterloos, M Van Landschoot, C Danneels, and B Martens for their technical assistance.

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Renal Division, Nephrology Section, 0K12, Ghent University Hospital, De Pintelaan 185, B9000, Ghent, Belgium

    J. Vanmassenhove, G. Glorieux, A. Dhondt, R. Vanholder & W. Van Biesen

  2. Intensive Care Unit, Ghent University Hospital, Ghent, Belgium

    E. Hoste

  3. Senior Clinical Investigator, Research Foundation Flanders, Flanders, Belgium

    E. Hoste

Authors
  1. J. Vanmassenhove
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  2. G. Glorieux
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  3. E. Hoste
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  4. A. Dhondt
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  5. R. Vanholder
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  6. W. Van Biesen
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Corresponding author

Correspondence to W. Van Biesen.

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Vanmassenhove, J., Glorieux, G., Hoste, E. et al. AKI in early sepsis is a continuum from transient AKI without tubular damage over transient AKI with minor tubular damage to intrinsic AKI with severe tubular damage. Int Urol Nephrol 46, 2003–2008 (2014). https://doi.org/10.1007/s11255-014-0822-y

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  • DOI: https://doi.org/10.1007/s11255-014-0822-y

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