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

• Published in: Critical care (London, England) Vol. 26; no. 1; p. 344
• Main Authors: Piedrafita, Alexis, Siwy, Justyna, Klein, Julie, Akkari, Amal, Amaya-Garrido, Ana, Mebazaa, Alexandre, Sanz, Anna Belen, Breuil, Benjamin, Montero Herrero, Laura, Marcheix, Bertrand, Depret, François, Fernandez, Lucie, Tardif, Elsa, Minville, Vincent, Alves, Melinda, Metzger, Jochen, Grossac, Julia, Mischak, Harald, Ortiz, Alberto, Gazut, Stéphane, Schanstra, Joost P, Faguer, Stanislas
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 07.11.2022; BioMed Central; BMC
• Subjects: Acute kidney injury; Acute Kidney Injury - diagnosis; Acute renal failure; Biochemistry, Molecular Biology; Biomarkers; Cardiac surgery; Care and treatment; Complications and side effects; Computer Science; Coronary artery bypass; Creatinine; Critical care; Genomics; Glomerular filtration rate; Health aspects; Heart failure; Heart surgery; Hospital patients; Humans; Intensive care unit; Kidney diseases; Life Sciences; Lipocalin-2; Measurement; Peptides; Prediction; Predictive Value of Tests; Prevention; Risk factors; Sepsis; Signal and Image Processing; Support vector machines; Urinary peptidomics; Urine; Germany; Urinary peptidomics; Cardiac surgery; Acute kidney injury; Intensive care unit; Prediction; kidney; acute kidney injury (AKI); signal processing; classification; biomarker; statistical analysis; peptide signature
• ISSN: 1364-8535; 1466-609X; 1364-8535; 1366-609X
• DOI: 10.1186/s13054-022-04193-9

The 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. In 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. A 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). An 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.