A universal predictive and mechanistic urinary peptide signature in acute kidney injury

Critical Care

Research

Julia Grossac¹  Elsa Tardif¹  François Depret²  Alexandre Mebazaa²  Alexis Piedrafita³  Stanislas Faguer³  Jochen Metzger⁴  Justyna Siwy⁴  Harald Mischak⁴  Ana Amaya-garrido⁵  Melinda Alves⁵  Lucie Fernandez⁵  Benjamin Breuil⁶  Julie Klein⁶  Joost P. Schanstra⁶  Laura Montero Herrero⁷  Anna Belen Sanz⁷  Alberto Ortiz⁷  Vincent Minville⁸  Bertrand Marcheix⁹  Stéphane Gazut^1,10  Amal Akkari^1,10 

[1] Department of Anesthesiology and Critical Care Medicine, University Hospital of Toulouse, 31000, Toulouse, France;Department of Anesthesiology, Critical Care and Burn Unit, Hôpitaux Universitaires Saint Louis-Lariboisière, Assistance Publique-Hôpitaux de Paris, Université Paris Diderot-Paris 7, Sorbonne Paris Cité, UMR-S 942, INSERM, France, INI-CRCT, ParisNancy, France;Department of Nephrology and Organ Transplantation, University Hospital of Toulouse, and French Intensive Care Renal Network, 31000, Toulouse, France;National Institute of Health and Medical Research (INSERM), UMR 1297, Institute of Cardiovascular and Metabolic Disease, 31000, Toulouse, France;University Paul Sabatier, Toulouse-III, 31000, Toulouse, France;Mosaiques Diagnostics GmbH, Hannover, Germany;National Institute of Health and Medical Research (INSERM), UMR 1297, Institute of Cardiovascular and Metabolic Disease, 31000, Toulouse, France;National Institute of Health and Medical Research (INSERM), UMR 1297, Institute of Cardiovascular and Metabolic Disease, 31000, Toulouse, France;University Paul Sabatier, Toulouse-III, 31000, Toulouse, France;School of Medicine, IIS-Fundación Jiménez Díaz, Autonomous University of Madrid, FRIAT and REDINREN, Madrid, Spain;University Paul Sabatier, Toulouse-III, 31000, Toulouse, France;Department of Anesthesiology and Critical Care Medicine, University Hospital of Toulouse, 31000, Toulouse, France;University Paul Sabatier, Toulouse-III, 31000, Toulouse, France;Department of Cardiac and Vascular Surgery, University Hospital of Toulouse, 31000, Toulouse, France;Université Paris-Saclay, CEA, List, 91120, Palaiseau, France;

关键词: Acute kidney injury;    Cardiac surgery;    Intensive care unit;    Urinary peptidomics;    Prediction;   

DOI  :  10.1186/s13054-022-04193-9

 received in 2022-06-30, accepted in 2022-10-07,  发布年份 2022

来源: Springer

【 摘 要 】

BackgroundThe delayed diagnosis of acute kidney injury (AKI) episodes and the lack of specificity of current single AKI biomarkers hamper its management. Urinary peptidome analysis may help to identify early molecular changes in AKI and grasp its complexity to identify potential targetable molecular pathways.MethodsIn derivation and validation cohorts totalizing 1170 major cardiac bypass surgery patients and in an external cohort of 1569 intensive care unit (ICU) patients, a peptide-based score predictive of AKI (7-day KDIGO classification) was developed, validated, and compared to the reference biomarker urinary NGAL and NephroCheck and clinical scores.ResultsA set of 204 urinary peptides derived from 48 proteins related to hemolysis, inflammation, immune cells trafficking, innate immunity, and cell growth and survival was identified and validated for the early discrimination (< 4 h) of patients according to their risk to develop AKI (OR 6.13 [3.96–9.59], p < 0.001) outperforming reference biomarkers (urinary NGAL and [IGFBP7].[TIMP2] product) and clinical scores. In an external cohort of 1569 ICU patients, performances of the signature were similar (OR 5.92 [4.73–7.45], p < 0.001), and it was also associated with the in-hospital mortality (OR 2.62 [2.05–3.38], p < 0.001).ConclusionsAn overarching AKI physiopathology-driven urinary peptide signature shows significant promise for identifying, at an early stage, patients who will progress to AKI and thus to develop tailored treatments for this frequent and life-threatening condition. Performance of the urine peptide signature is as high as or higher than that of single biomarkers but adds mechanistic information that may help to discriminate sub-phenotypes of AKI offering new therapeutic avenues.

【 授权许可】

CC BY   
© The Author(s) 2022. corrected publication 2022

【 图 表 】

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