Volume 82, August 2024, 154816Author links open overlay panel, , , , , , , , , , , , , , , Highlights•

Urinary C-C motif chemokine ligand 14 (CCL14) is a newly discovered biomarker for persistent AKI.

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We sought to determine how CCL14 test results might change clinical recommendations for AKI.

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Twelve experts conducted a modified Delphi process to evaluate patients at risk for persistent AKI.

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Nine (82%) recommendations for clinical actions were significantly impacted by CCL14 results.

AbstractPurpose

Urinary C-C motif chemokine ligand 14 (CCL14) is a strong predictor of persistent stage 3 acute kidney injury (AKI). Multiple clinical actions are recommended for AKI but how these are applied in individual patients and how the CCL14 test results may impact their application is unknown.

Methods

We assembled an international panel of 12 experts and conducted a modified Delphi process to evaluate patients at risk for persistent stage 3 AKI (lasting 72 hours or longer). Using a Likert scale, we rated 11 clinical actions based on international guidelines applied to each case before and after CCL14 testing and analyzed the association between the strength and direction of recommendations and CCL14 results.

Results

The strength and direction of clinical recommendations were strongly influenced by CCL14 results (P < 0.001 for the interaction). Nine (82%) recommendations for clinical actions were significantly impacted by CCL14 results (P < 0.001 comparing low to highest CCL14 risk category).

Conclusions

Most recommendations for care of patients with stage 2-3 by an international panel of experts were strongly modified by CCL14 test results. This work should set the stage for clinical practice protocols and studies to determine the effects of recommended actions informed by CCL14.

Section snippetsBackground

For patients with stage 2-3 acute kidney injury (AKI), the urinary biomarker chemokine ligand CCL14 is a strong predictor of persistent stage 3 AKI [[1], [2], [3], [4], [5]]. Given the considerable uncertainty regarding the course of AKI, the ability to predict kidney recovery could significantly impact the care of patients. However, the approach to patients with AKI and therefore at risk for persistent stage 3 AKI is not standardized. The KDIGO clinical practice guideline for AKI [6]

Study subjects

We assembled a panel of twelve experts in AKI from Europe (LF, MJ, MO, JP, CR, AS, AZ) and North America (SMB, SD, JAK, JLK, AT), representing Critical Care and Nephrology. Experts were all practicing clinicians, selected from the top 0.3% of published authors on AKI worldwide between 2013 and 2023 (expertscape.com accessed October 4, 2023). Additional criteria included balancing specialty, and country of origin to the extent possible. Written informed consent was obtained from each participant.

Recommended actions and associations with CCL14 risk categories

Our primary analysis tested whether clinical recommendations were influenced by CCL14 results (categorized as Lowest, Increased or Highest Risk) defined by two clinical cutoff values described previously [3]. This analysis revealed that overall, the strength and direction of clinical recommendations were strongly influenced by CCL14 results (P < 0.001 for CCL14, clinical action, and their interaction). Given this result, we examined pairwise comparisons between the three CCL14 risk categories

Discussion

For six clinical cases, twelve experts from Europe and North America significantly modified their recommendations for care based on urinary CCL14 test results corresponding to three categories of risk (lowest, increased, and highest) for developing persistent stage 3 AKI. However, some clinical actions were clearly more impacted than others. Effects of CCL14 on expert recommendations were highly significant (P <0.001) for all clinical actions except measuring serum creatinine and use of

Ethics approval and consent to participate

All participants provided written consent.

Consent for publication

Not applicable.

Source of support

bioMérieux

Funding

This work was funded by bioMérieux.

CRediT authorship contribution statement

John A. Kellum: Writing – review & editing, Writing – original draft, Supervision, Project administration, Methodology, Investigation, Funding acquisition, Conceptualization. Sean M. Bagshaw: Writing – review & editing, Methodology, Investigation, Conceptualization. Sevag Demirjian: Writing – review & editing, Investigation, Conceptualization. Lui Forni: Writing – review & editing, Methodology, Investigation. Michael Joannidis: Writing – review & editing, Investigation, Conceptualization. J.

Declaration of competing interest

SB, SD, LF, MJ, JAK, JLK, MO, JP, CR, AS, AT, AZ disclose consulting fees paid by bioMérieux. JPK, TK, and PM were full-time employees of Astute Medical/bioMérieux when this work was conducted. JDLS is a full-time employee of bioMérieux.

Acknowledgments

None.

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