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. 2025 May 20;29(1):204.
doi: 10.1186/s13054-025-05439-y.

Biomarkers in acute kidney injury settings to predict interventions and outcomes: the MARKISIO study

Khalil Chaïbi  1   2 , Adrien Picod  3 , Marouane Boubaya  4 , Sarah Tubiana  5 , Vincent Jullien  6 , Sophie Magreault  6 , Sandrine Placier  2 , Jérémie Mallet  2 , Guillaume Louis  7 , Laurent Martin-Lefevre  8 , Dimitri Titeca-Beauport  9 , Béatrice La Combe  10 , Sébastien Besset  11 , Julio Badie  12 , Guillaume Chevrel  13 , Nicolas Chudeau  14 , Saber Barbar  15 , Christophe Vinsonneau  16 , Jean-Marie Forel  17 , Didier Thevenin  18 , Guillaume Lacave  19 , Saad Nseir  20 , Johanna Oziel  1 , Julien Mayaux  21 , Kada Klouche  22 , Jean Reignier  23 , Jean-Damien Ricard  11   24 , Jean-Pierre Quenot  25   26 , Alexandre Mebazaa  3   27 , Feriel Azibani  3 , Didier Dreyfuss  2   11   28 , Stéphane Gaudry  29   30   31   32   33
Affiliations

Biomarkers in acute kidney injury settings to predict interventions and outcomes: the MARKISIO study

Khalil Chaïbi et al. Crit Care. .

Abstract

Introduction: Predicting the need for renal replacement therapy (RRT) in acute kidney injury (AKI) remains challenging. The utility of biomarkers was explored during previous studies which were biased as RRT indications relied on clinician opinion rather than evidence. Those studies preceded trials that clarified RRT initiation criteria. We aimed to assess biomarkers in predicting criteria for RRT initiation in severe AKI patients.

Material and methods: This is an ancillary study of the AKIKI2 trial. Patients with severe AKI (stage 3) receiving invasive mechanical ventilation and/or vasopressors were included. Blood and urine samples were collected within 12 h after the occurrence of severe AKI when feasible, depending on the availability of trained research staff and appropriate sample storage infrastructure. The primary endpoint was the onset of precise criteria for RRT initiation within 72 h after severe AKI. We analyzed routine serum biomarkers (pH, serum potassium, serum creatinine) and novel urinary and serum biomarkers (CCL14, KIM1, nicotinamide and its metabolites, cDPP3, plasma proenkephalin A 119-159).

Results: Among the 256 patients, 101 (39%) met at least one criterion for RRT initiation or died within 72 h. No biomarker demonstrated satisfactory predictive performance for the primary endpoint. No novel biomarker was significantly associated with the occurrence of MAKE60. In multivariable analysis, 'SAPSIII' and 'Serum potassium level at D0' were significantly associated with the occurrence of MAKE60.

Conclusion: Neither routine nor novel biomarkers demonstrated conclusive predictive accuracy for the need for RRT in severe AKI patients. Given evidence-based criteria for initiating RRT, the tested biomarkers may not effectively guide RRT initiation.

Keywords: Acute kidney injury; Biomarkers; Renal replacement therapy.

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Conflict of interest statement

Declarations. Ethics approval and consent to participate: The study protocol, including the biobank collection, was approved by the competent French legal authority (Comité de Protection des Personnes de Sud-Est V) for all participating centers. Patients (or their surrogates) who were included were informed about the study both verbally and with a written document in accordance with French law. Consent for publication: Not applicable. Competing interests: The AKIKI 2 trial was promoted by the Assistance Publique—Hôpitaux de Paris and funded by a grant of the French Ministry of Health (Programme Hospitalier de Recherche Clinique 2016; AOM16278). Circulating DPP3 concentration was measured free of charge by 4TEEN4 Pharmaceuticals GmbH, Hennigsdorf, Germany Plasma proenkephalin A 119-159 concentration was measured free of charge by Sphingotec GmbH, Hennigsdorf, Germany The Cardiovascular Markers in Stress Conditions Research Group is supported by a research grant from 4TEEN4 Pharmaceuticals GmbH, which allowed salary support for A. Picod. A. Mebazaa received fees as a member of advisory board from Sphingotec. The other authors declare no competing interest regarding the submitted work.

Figures

Fig. 1
Fig. 1
Patient flow diagram. RRT: renal replacement therapy
Fig. 2
Fig. 2
Area under the ROC curve (AUC) for prediction of the need for RRT within 72 h. Routine biomarkers refer to pH, serum potassium concentration and serum creatinine concentration (A). Novel urinary biomarkers refer to CCL14 and KIM1 (B). Novel plasma biomarkers refer to DPP3 and PenKid (C). Nicotinamide and its metabolites are also considered novel biomarkers but are presented separately (D). RRT: renal replacement therapy
See this image and copyright information in PMC

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