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01-12-2020 | Acute Kidney Injury | Research

Two subphenotypes of septic acute kidney injury are associated with different 90-day mortality and renal recovery

Authors: Renske Wiersema, Sakari Jukarainen, Suvi T. Vaara, Meri Poukkanen, Päivi Lakkisto, Hector Wong, Adam Linder, Iwan C. C. van der Horst, Ville Pettilä

Published in: Critical Care | Issue 1/2020

Abstract

Background

The pathophysiology of septic acute kidney injury is inadequately understood. Recently, subphenotypes for sepsis and AKI have been derived. The objective of this study was to assess whether a combination of comorbidities, baseline clinical data, and biomarkers could classify meaningful subphenotypes in septic AKI with different outcomes.

Methods

We performed a post hoc analysis of the prospective Finnish Acute Kidney Injury (FINNAKI) study cohort. We included patients admitted with sepsis and acute kidney injury during the first 48 h from admission to intensive care (according to Kidney Disease Improving Global Outcome criteria). Primary outcomes were 90-day mortality and renal recovery on day 5. We performed latent class analysis using 30 variables obtained on admission to classify subphenotypes. Second, we used logistic regression to assess the association of derived subphenotypes with 90-day mortality and renal recovery on day 5.

Results

In total, 301 patients with septic acute kidney injury were included. Based on the latent class analysis, a two-class model was chosen. Subphenotype 1 was assigned to 133 patients (44%) and subphenotype 2 to 168 patients (56%). Increased levels of inflammatory and endothelial injury markers characterized subphenotype 2. At 90 days, 29% of patients in subphenotype 1 and 41% of patients in subphenotype 2 had died. Subphenotype 2 was associated with a lower probability of short-term renal recovery and increased 90-day mortality.

Conclusions

In this post hoc analysis, we identified two subphenotypes of septic acute kidney injury with different clinical outcomes. Future studies are warranted to validate the suggested subphenotypes of septic acute kidney injury.

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Pickkers P, Ostermann M, Joannidis M, Zarbock A, Hoste E, Bellomo R, et al. The intensive care medicine agenda on acute kidney injury. Intensive Care Med. Department of Intensive Care Medicine (710), Radboud University Medical Centre, Geert Grooteplein Zuid 10, P.O. Box 9101, 6500 HB, Nijmegen, The Netherlands.; Department of Critical Care, Guy’s and St Thomas’ Hospital, King’s College London, Lon (TRUNCATED; 2017;.

Nisula S, Kaukonen K-M, Vaara ST, Korhonen A-M, Poukkanen M, Karlsson S, et al. Incidence, risk factors and 90-day mortality of patients with acute kidney injury in Finnish intensive care units: the FINNAKI study. Intensive Care Med. 2013;39:420–8 Available from: https://doi.org/10.1007/s00134-012-2796-5.CrossRefPubMed

Hoste EAJ, Kellum JA, Selby NM, Zarbock A, Palevsky PM, Bagshaw SM, et al. Global epidemiology and outcomes of acute kidney injury. Nat Rev Nephrol. England: Nature Publishing Group; 2018 [cited 2018 Sep 4];14. Available from: http://www.nature.com/articles/s41581-018-0052-0.

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.CrossRef

Mildh H, Pettila V, Korhonen AM, Karlsson S, Ala-Kokko T, Reinikainen M, et al. Three-year mortality in 30-day survivors of critical care with acute kidney injury: data from the prospective observational FINNAKI study. Ann Intensive Care. 2016;6:118.CrossRefPubMed

Wald R, Quinn RR, Adhikari NK, Burns KE, Friedrich JO, Garg AX, et al. Risk of chronic dialysis and death following acute kidney injury. Am J Med. Elsevier; 2012 [cited 2018 Sep 19];125:585–93. Available from: https://www.sciencedirect.com/science/article/pii/S0002934312000939?via%3Dihub.

Pettilä V, Bellomo R. Understanding acute kidney injury in sepsis. Intensive Care Med. Springer Berlin Heidelberg; 2014 [cited 2018 Sep 4];40:1018–20. Available from: http://link.springer.com/10.1007/s00134-014-3313-9.

Langenberg C, Bagshaw SM, May CN, Bellomo R. The histopathology of septic acute kidney injury: a systematic review. Crit Care; 2008 [cited 2018 Sep 19];12:R38. Available from: http://ccforum.biomedcentral.com/articles/10.1186/cc6823.

Kinsey GR, Okusa MD. Pathogenesis of acute kidney injury: foundation for clinical practice. Am J Kidney Dis; 2011 [cited 2018 Sep 19];58:291–301. Available from: http://www.ncbi.nlm.nih.gov/pubmed/21530035.

10.

Calfee CS, Delucchi KL, Sinha P, Matthay MA, Hackett J, Shankar-Hari M, et al. Acute respiratory distress syndrome subphenotypes and differential response to simvastatin: secondary analysis of a randomised controlled trial. Lancet Respir Med; 2018 [cited 2018 Sep 4];6:691–8. Available from: https://www.sciencedirect.com/science/article/pii/S2213260018301772?via%3Dihub.

11.

Lawler PR, Fan E. Heterogeneity and phenotypic stratification in acute respiratory distress syndrome. Lancet Respir Med; 2018 [cited 2018 Sep 4];6:651–3. Available from: https://www.thelancet.com/journals/lanres/article/PIIS2213-2600(18)30287-X/abstract.

12.

Seymour CW, Kennedy JN, Wang S, Chang C-CH, Elliott CF, Xu Z, et al. Derivation, Validation, and Potential Treatment Implications of Novel Clinical Phenotypes for Sepsis. JAMA; 2019 [cited 2019 Jun 17];321:2003. Available from: http://jama.jamanetwork.com/article.aspx?doi=10.1001/jama.2019.5791.

13.

Bhatraju PK, Zelnick LR, Herting J, Katz R, Mikacenic C, Kosamo S, et al. Identification of acute kidney injury subphenotypes with differing molecular signatures and responses to vasopressin therapy. Am J Respir Crit Care Med; 2019 [cited 2019 Jun 17];199:863–72. Available from: https://www.atsjournals.org/doi/10.1164/rccm.201807-1346OC.

14.

Iwashyna TJ, Burke JF, Sussman JB, Prescott HC, Hayward RA, Angus DC. Implications of heterogeneity of treatment effect for reporting and analysis of randomized trials in critical care. Am J Respir Crit Care Med; 2015 [cited 2018 Sep 4];192:1045–51. Available from: http://www.atsjournals.org/doi/10.1164/rccm.201411-2125CP.

15.

Schaub JA, Heung M. Precision Medicine in acute kidney injury: a promising future? Am J Respir Crit Care Med; 2019 [cited 2019 Jun 17];199:814–6. Available from: https://www.atsjournals.org/doi/10.1164/rccm.201810-2032ED.

16.

Peters E, Antonelli M, Wittebole X, Nanchal R, François B, Sakr Y, et al. A worldwide multicentre evaluation of the influence of deterioration or improvement of acute kidney injury on clinical outcome in critically ill patients with and without sepsis at ICU admission: results from The Intensive Care Over Nations audit. Crit Care ; 2018 [cited 2018 Sep 4];22:188. Available from: https://ccforum.biomedcentral.com/articles/10.1186/s13054-018-2112-z.

17.

KDIGO Clinical practice guideline for acute kidney injury. Kidney Int Suppl. 2012;2. Available from: https://doi.org/10.1038/kisup.2012.1.

18.

Barry R, James MT. Guidelines for classification of acute kidney diseases and disorders. Nephron. Switzerland: Karger Publishers; 2015 [cited 2018 Sep 4];131:221–6. Available from: https://www.karger.com/Article/FullText/441425#ref11.

19.

Endre ZH. Assessing renal recovery after acute kidney injury: can biomarkers help? Nephron.; 2018 [cited 2018 Sep 4];140:86–9. Available from: https://www.karger.com/Article/FullText/492290#ref12.

20.

Bagshaw SM, Bennett M, Devarajan P, Bellomo R. Urine biochemistry in septic and non-septic acute kidney injury: a prospective observational study. J Crit Care; 2013 [cited 2018 Sep 4];28:371–8. Available from: https://www.sciencedirect.com/science/article/pii/S0883944112003346?via%3Dihub.

21.

Gayat E, Touchard C, Hollinger A, Vieillard-Baron A, Mebazaa A, Legrand M. Back-to-back comparison of penKID with NephroCheck® to predict acute kidney injury at admission in intensive care unit: a brief report. Crit Care ; 2018 [cited 2018 Sep 19];22:24. Available from: https://ccforum.biomedcentral.com/articles/10.1186/s13054-018-1945-9.

22.

Nisula S, Yang R, Kaukonen K-M, Vaara ST, Kuitunen A, Tenhunen J, et al. The urine protein NGAL predicts renal replacement therapy, but not acute kidney injury or 90-day mortality in critically ill adult patients. Anesth Analg. 2014 [cited 2018 Sep 19];119:95–102. Available from: http://www.ncbi.nlm.nih.gov/pubmed/24806144.

23.

Marttinen M, Wilkman E, Petäjä L, Suojaranta-Ylinen R, Pettilä V, Vaara ST. Association of plasma chloride values with acute kidney injury in the critically ill - a prospective observational study. Acta Anaesthesiol Scand . Wiley/Blackwell (10.1111); 2016 [cited 2018 Sep 4];60:790–9. Available from: http://doi.wiley.com/10.1111/aas.12694.

24.

Nisula S, Yang R, Poukkanen M, Vaara SST, Kaukonen KMK-M, Tallgren M, et al. Predictive value of urine interleukin-18 in the evolution and outcome of acute kidney injury in critically ill adult patients. Br J Anaesth ; 2015 [cited 2018 Sep 4];114:460–8. Available from: https://www.sciencedirect.com/science/article/pii/S0007091217318123?via%3Dihub.

25.

Mårtensson J, Vaara ST, Pettilä V, Ala-Kokko T, Karlsson S, Inkinen O, et al. Assessment of plasma endostatin to predict acute kidney injury in critically ill patients. Acta Anaesthesiol Scand . Wiley/Blackwell (10.1111); 2017 [cited 2018 Sep 19];61:1286–95. Available from: http://doi.wiley.com/10.1111/aas.12988.

26.

Hästbacka J, Linko R, Tervahartiala T, Varpula T, Hovilehto S, Parviainen I, et al. Serum MMP-8 and TIMP-1 in critically ill patients with acute respiratory failure: TIMP-1 is associated with increased 90-day mortality. Anesth Analg. 2014 [cited 2018 Sep 19];118:790–8. Available from: https://insights.ovid.com/crossref?an=00000539-201404000-00016.

27.

Vaara ST, Hollmén M, Korhonen A-M, Maksimow M, Ala-Kokko T, Salmi M, et al. Soluble CD73 in critically ill septic patients – data from the prospective FINNAKI study. Khodarahmi R, editor. PLoS One; 2016 [cited 2018 Sep 19];11:e0164420. Available from: http://dx.plos.org/10.1371/journal.pone.0164420.

28.

Tverring J, Vaara ST, Fisher J, Poukkanen M, Pettilä V, Linder A. Heparin-binding protein (HBP) improves prediction of sepsis-related acute kidney injury. Ann Intensive Care; 2017 [cited 2018 Sep 4];7:105. Available from: http://annalsofintensivecare.springeropen.com/articles/10.1186/s13613-017-0330-1.

29.

Wong HR, Cvijanovich NZ, Anas N, Allen GL, Thomas NJ, Bigham MT, et al. A multibiomarker-based model for estimating the risk of septic acute kidney injury. Crit Care Med. 2015 [cited 2019 Jun 19];43:1646–53. Available from: https://insights.ovid.com/crossref?an=00003246-201508000-00012.

30.

Vaara ST, Lakkisto P, Immonen K, Tikkanen I, Ala-Kokko T, Pettilä V, et al. Urinary biomarkers indicative of apoptosis and acute kidney injury in the critically ill. Ricci Z, editor. PLoS One ; 2016 [cited 2018 Sep 4];11:e0149956. Available from: http://dx.plos.org/10.1371/journal.pone.0149956.

31.

Kellum JA, Sileanu FE, Bihorac A, Hoste EAJ, Chawla LS. Recovery after acute kidney injury. Am J Respir Crit Care Med. 2017;195:784–91.CrossRefPubMed

32.

Poukkanen M, Vaara ST, Pettilä V, Kaukonen K-MK-M, Korhonen A-MA-M, Hovilehto S, et al. Acute kidney injury in patients with severe sepsis in Finnish Intensive Care Units. Acta Anaesthesiol Scand. England; 2013 [cited 2018 Sep 4];57:863–72. Available from: http://www.stat.fi.

33.

Kellum JA. Diagnosis, evaluation, and management of acute kidney injury: a KDIGO summary (part 1). Crit Care. 2013;17. Available from: https://doi.org/10.1186/cc11454.

34.

Bone RC, Balk RA, Cerra FB, Dellinger RP, Fein AM, Knaus WA, et al. Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. Chest ; 1992 [cited 2018 Sep 4];101:1644–55. Available from: https://www.sciencedirect.com/science/article/pii/S001236921638415X?via%3Dihub.

35.

Basu RK, Standage SW, Cvijanovich NZ, Allen GL, Thomas NJ, Freishtat RJ, et al. Identification of candidate serum biomarkers for severe septic shock-associated kidney injury via microarray. Crit Care. 2011 [cited 2019 Jun 19];15:R273. Available from: http://ccforum.biomedcentral.com/articles/10.1186/cc10554.

36.

37.

Wong HR, Cvijanovich NZ, Anas N, Allen GL, Thomas NJ, Bigham MT, et al. A multibiomarker-based model for estimating the risk of septic acute kidney injury. Crit Care Med. 2015;43:1646–53.CrossRefPubMed

38.

Sood MM, Shafer LA, Ho J, Reslerova M, Martinka G, Keenan S, et al. Early reversible acute kidney injury is associated with improved survival in septic shock. J Crit Care. 2014;29:711–7.CrossRef

39.

Bhatraju PK, Mukherjee P, Robinson-Cohen C, O’Keefe GE, Frank AJ, Christie JD, et al. Acute kidney injury subphenotypes based on creatinine trajectory identifies patients at increased risk of death. Crit Care. 2016;20:372.CrossRefPubMed

40.

Famulski KS, de Freitas DG, Kreepala C, Chang J, Sellares J, Sis B, et al. Molecular phenotypes of acute kidney injury in kidney transplants. J Am Soc Nephrol. 2012;23:948–58.CrossRefPubMed

41.

Xu K, Rosenstiel P, Paragas N, Hinze C, Gao X, Huai Shen T, et al. Unique transcriptional programs identify subtypes of AKI. J Am Soc Nephrol. 2017;28:1729–40.CrossRef

42.

Seymour CW, Kennedy JN, Wang S, Chang C-CH, Elliott CF, Xu Z, et al. Derivation, validation, and potential treatment implications of novel clinical phenotypes for sepsis. JAMA. 2019;321:2003.CrossRefPubMed

43.

Russell JA, Walley KR, Singer J, Gordon AC, Hébert PC, Cooper DJ, et al. Vasopressin versus norepinephrine infusion in patients with septic shock. N Engl J Med ; 2008 [cited 2019 Jun 19];358:877–87. Available from: http://www.nejm.org/doi/abs/10.1056/NEJMoa067373.

44.

Schaub JA, Heung M. Precision medicine in acute kidney injury: a promising future? Am J Respir Crit care med. Am Thoracic Soc. 2019;199:814–6.

45.

Castela Forte J, Perner A, van der Horst ICC. The use of clustering algorithms in critical care research to unravel patient heterogeneity. Intensive Care Med; 2019 [cited 2019 Jun 27];1–4. Available from: http://link.springer.com/10.1007/s00134-019-05631-z.

Title: Two subphenotypes of septic acute kidney injury are associated with different 90-day mortality and renal recovery
Authors: Renske Wiersema
Sakari Jukarainen
Suvi T. Vaara
Meri Poukkanen
Päivi Lakkisto
Hector Wong
Adam Linder
Iwan C. C. van der Horst
Ville Pettilä
Publication date: 01-12-2020
Publisher: BioMed Central
Keywords: Acute Kidney Injury
Septicemia
Septicemia
Acute Kidney Injury
Biomarkers
Published in: Critical Care / Issue 1/2020
Electronic ISSN: 1364-8535
DOI: https://doi.org/10.1186/s13054-020-02866-x

At a glance: The STEP trials

Springer Medicine

Two subphenotypes of septic acute kidney injury are associated with different 90-day mortality and renal recovery

Abstract

Background

Methods

Results

Conclusions

At a glance: The STEP trials

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

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