Unsupervised clustering reveals phenotypes of AKI in ICU COVID-19 patients

  1. David Legouis
  2. Gilles Criton
  3. Benjamin Assouline
  4. Christophe Le Terrier
  5. Sebastian Sgardello
  6. Jérôme Pugin
  7. Elisa Marchi
  8. Frédéric Sangla

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Abstract

Acute Kidney Injury (AKI) is a very frequent condition, occurring in about one in three patients admitted to an intensive care unit (ICU). AKI is a syndrome defined as a sudden decrease in glomerular filtration rate. However, this unified definition does not reflect the various mechanisms involved in AKI pathophysiology, each with its own characteristics and sensitivity to therapy. In this study, we aimed at developing an innovative machine learning based method able to subphenotype AKI according to its pattern of risk factors.

Methods

We adopted a three-step pipeline of analyses. First, we looked for factors associated with AKI using a generalized additive model. Second, we calculated the importance of each identified AKI related factor in the estimated AKI risk to find the main risk factor for AKI, at the single patient level. Lastly, we clusterized AKI patients according to their profile of risk factors and compared the clinical characteristics and outcome of every cluster. We applied this method to a cohort of severe COVID-19 patients hospitalized in the ICU of the Geneva University Hospitals.

Results

Among the 248 patients analyzed, we found 7 factors associated with AKI development. Using the individual expression of these factors, we identified three groups of AKI patients, based on the use of Lopinavir/Ritonavir, baseline eGFR, use of dexamethasone and AKI severity. The three clusters expressed distinct characteristics in terms of AKI severity and recovery, metabolic patterns and hospital mortality.

Conclusion

We propose here a new method to phenotype AKI patients according to their most important individual risk factors for AKI development. When applied to an ICU cohort of COVID-19 patients, we were able to differentiate three groups of patients. Each expressed specific AKI characteristics and outcomes, which probably reflect a distinct pathophysiology.

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  1. Version published to 10.3389/fmed.2022.980160
  2. ScreenIT

    SciScore for 10.1101/2022.03.11.22272259: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    NIH rigor criteria are not applicable to paper type.

    Table 2: Resources

    No key resources detected.

    Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).

    Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:
    Our study has some limitations. Firstly, the study was single-centred which limits the extent of our results. Secondly, being a retrospective study, procedures and therapeutic strategies may have changed during the study period. Nonetheless, we feel we have provided a generalizable pipeline that may be applied to various datasets to identify patients with different outcomes and therapeutic sensitivity.

    Results from TrialIdentifier: No clinical trial numbers were referenced.

    Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

    Results from JetFighter: We did not find any issues relating to colormaps.

    Results from rtransparent:
    • Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
    • Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
    • No protocol registration statement was detected.

    Results from scite Reference Check: We found no unreliable references.

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  3. Version published to 10.1101/2022.03.11.22272259v1 on medRxiv