Subclinical and clinical acute kidney injury share similar urinary peptide signatures and prognosis

Louis Boutin; Agnieszka Latosinska; Harald Mischak; Benjamin Deniau; Ayu Asakage; Matthieu Legrand; Etienne Gayat; Alexandre Mebazaa; Christos E Chadjichristos; François Depret

doi:10.1007/s00134-023-07198-2

Subclinical and clinical acute kidney injury share similar urinary peptide signatures and prognosis

Intensive Care Med. 2023 Oct;49(10):1191-1202. doi: 10.1007/s00134-023-07198-2. Epub 2023 Sep 5.

Authors

Louis Boutin^{1

2

3}, Agnieszka Latosinska⁴, Harald Mischak⁴, Benjamin Deniau^{1

2}, Ayu Asakage², Matthieu Legrand⁵, Etienne Gayat^{1

2}, Alexandre Mebazaa^{1

2}, Christos E Chadjichristos³, François Depret^{6

7}

Affiliations

¹ Department of Anesthesiology, Critical Care Medicine and Burn Unit, FHU PROMICE AP-HP, Saint Louis and DMU Parabol, AP-HP, Université Paris Cité, 75010, Paris, France.
² UMR-942, MASCOT, INSERM, Cardiovascular Markers in Stress Condition, Université de Paris, 75010, Paris, France.
³ UMR-S1155, Faculty of Medicine, INSERM Bâtiment Recherche, Tenon Hospital Sorbonne University, 75020, Paris, France.
⁴ Mosaiques Diagnostics GmbH, Hannover, Germany.
⁵ Department of Anesthesiology and Peri-Operative Medicine, Division of Critical Care Medicine, University of California, UCSF Medical Center, 500 Parnassus Ave, San Francisco, CA, 94143, USA.
⁶ Department of Anesthesiology, Critical Care Medicine and Burn Unit, FHU PROMICE AP-HP, Saint Louis and DMU Parabol, AP-HP, Université Paris Cité, 75010, Paris, France. francois.depret@aphp.fr.
⁷ UMR-942, MASCOT, INSERM, Cardiovascular Markers in Stress Condition, Université de Paris, 75010, Paris, France. francois.depret@aphp.fr.

PMID: 37670154
DOI: 10.1007/s00134-023-07198-2

Abstract

Purpose: Acute kidney injury (AKI) is a frequent and severe condition in intensive care units (ICUs). In 2020, the Acute Dialysis Quality Initiative (ADQI) group proposed a new stage of AKI, referred to as stage 1S, which represents subclinical disease (sAKI) defined as a positive biomarker but no increase in serum creatinine (sCr). This study aimed to determine and compare the urinary peptide signature of sAKI as defined by biomarkers.

Methods: This is an ancillary analysis of the prospective, observational, multinational FROG-ICU cohort study. AKI was defined according to the Kidney Disease Improving Global Outcome definition (AKI_KDIGO). sAKI was defined based on the levels of the following biomarkers, which exceeded the median value: neutrophil gelatinase-associated lipocalin (pNGAL, uNGAL), cystatin C (pCysC, uCysC), proenkephalin A 119-159 (pPENKID) and liver fatty acid binding protein (uLFABP). Urinary peptidomics analysis was performed using capillary electrophoresis-mass spectrometry. Samples were collected at the time of study inclusion.

Results: One thousand eight hundred eighty-five patients had all biomarkers measured at inclusion, which included 1154 patients without AKI (non-AKI_KDIGO subgroup). The non-AKI_KDIGO subgroup consisted of individuals at a median age of 60 years [48, 71], among whom 321 (27.8%) died. The urinary peptide signatures of sAKI, regardless of the biomarkers used for its definition, were similar to the urinary peptide signatures of AKI_KDIGO (inflammation, haemolysis, and endothelial dysfunction). These signatures were also associated with 1-year mortality.

Conclusion: Biomarker-defined sAKI is a common and severe condition observed in patients within intensive care units with a urinary peptide signature that is similar to that of AKI, along with a comparable prognosis.

Keywords: Intensive care unit; Renal biomarkers; Subclinical AKI; Urinary peptide signature.

Abstract

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