Assessing the role of Chemokine (C–C motif) ligand 14 in AKI: a European consensus meeting

Abstract

Background

Urinary Chemokine (C–C motif) ligand 14 (CCL14) is a biomarker associated with persistent severe acute kidney injury (AKI). There is limited data to support the implementation of this AKI biomarker to guide therapeutic actions.

Methods

Sixteen AKI experts with clinical CCL14 experience participated in a Delphi-based method to reach consensus on when and how to potentially use CCL14. Consensus was defined as ≥ 80% agreement (participants answered with ‘Yes’, or three to four points on a five-point Likert Scale).

Results

Key consensus areas for CCL14 test implementation were: identifying challenges and mitigations, developing a comprehensive protocol and pairing it with a treatment plan, and defining the target population. The majority agreed that CCL14 results can help to prioritize AKI management decisions. CCL14 levels above the high cutoff (> 13 ng/mL) significantly changed the level of concern for modifying the AKI treatment plan (p < 0.001). The highest level of concern to modify the treatment plan was for discussions on renal replacement therapy (RRT) initiation for CCL14 levels > 13 ng/mL. The level of concern for discussion on RRT initiation between High and Low, and between Medium and Low CCL14 levels, showed significant differences.

Conclusion

Real world urinary CCL14 use appears to provide improved care options to patients at risk for persistent severe AKI. Experts believe there is a role for CCL14 in AKI management and it may potentially reduce AKI-disease burden. There is, however, an urgent need for evidence on treatment decisions and adjustments based on CCL14 results.

Keywords:

• Biomarker testing experience
• C‑C motif chemokine ligand 14 (CCL14)
• consensus
• critical care nephrology
• persistent acute kidney injury

Authors’ contributions

All authors participated in the discussions in the Round Table Meeting as well as the questionnaire rounds, critically reviewed the manuscript providing interpretation of the data and their implications and provided approval for the final version to be published. The results presented in this paper have not been published previously in whole or in part. This publication was subject to review by internal employees from Baxter Healthcare Corporation prior to submission for protection of Confidential Information. However, the Authors retain full responsibility for the content of this publication.

Disclosure statement

• Funding

  • The report was drafted by independent medical writers from a contract research organization (Avania) who were reimbursed by Baxter in line with Good Publication Practice 3 [26].

• Competing interests

  • All authors received financial travel and accommodation compensation from Baxter for attending the meeting.

  • JLK has received research funding from NIH, Astute Medical-Biomerieux, and Fresenius medical; received consulting Fees from Seastar Medical, Biomerieux, Mallinckrodt, Novartis, Guard Therapeutics, and Alexion; received honoraria from American Society of Nephrology and ISICEM, received royalties from Wolters Kluwer for author/editor duties, and participated in Data safety monitoring/advisory board for Alexion and Novartis.

  • CA received honorary from Baxter for the pre- and post-survey meeting of this manuscript; and received CCL14 tests and Astute meter from Baxter

  • JB has nothing to disclose

  • SC has received research funding from Baxter; consulting fees from Baxter; honoraria from Baxter; and participated in an Advisory Board for Baxter.

  • MG has received payments from Baxter supporting the present manuscript; received travel/meeting support from Baxter Spain; and participated in an TPE advisory board fro Baxter Spain

  • LG received travel/meeting support from Baxter

  • MJ has received consulting fees from Baxter, AmPharma, Biomerieux and Sphingotec; honoraria from Baxter; Biomerieux, and AOP; and research support from Baxter and Fresenius medical.

  • PJ has received grants from Baxter and consulting fees from Baxter

  • CK received consultancy fees from Baxter; and received free CCL14 tests from Baxter.

  • SL has nothing to disclose

  • AM has received consulting fees from Baxter

  • MO has been a member of the Executive Committee of the Intensive Care Society UK and an expert advisor to NICE UK.

  • NP received speakers fee from Baxter

  • JP has recent consultancy agreements with Mission Therapeutics, Jafron Biomedical, Paion Ltd, Baxter Inc, Biomerieux SA; received research support from Astute Medical-Biomerieux; Speaker’s fees and hospitality from Baxter Inc and Nikkiso; meeting and/or travel support from Jafron Biomedical and Nikkiso. JP serves on a Data Safety Monitoring Board (DMSB) for Novartis. JP has fulfilled the role of chair for an AKI Section in the European Society of Intensive Care Medicine, and Co-chair for the UK Kidney Research Consortium AKI section.

  • JS has received support from Baxter for medical writing, submission and APCs for this manuscript; and consulting fees from Baxter.

  • AZ has received consulting fees from Astute Medical-Biomerieux, Baxter, Bayer, Novartis, Guard Therapeutics, AM-Pharma, Paion, and Alexion; research funding from Paion, Astute Medical-Biomerieux, Fresenius medical, and Baxter; speakers fees from Astute Medical-Biomerieux, Fresenius medical, Paion, and Baxter; and travel support from Sphingotec and Paion. AZ has fulfilled editor roles for Nature (Anästhesist) and A&A.

  • JE and KH are full-time employees of Baxter International with ownership interest.

  • LF has received research support from Baxter; Honoria from Baxter and Jafron; consulting fees from SphingoTec; and has personal stock in Spiden.

Data availability statement

The data underlying this article are available in the article and in its online supplementary material.

Additional information

Funding

The meeting and associated expenses as well as the publication of this research was supported by Baxter Inc.

Reimbursed by Baxter Inc., statistical analysis support was provided by Razieh Taghavi of Avania B.V, and manuscript writing support was provided by Els Beijer and Kim van Noort of Avania B.V.