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

Abstract

Background 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. Methods 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. Results 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). Conclusions 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.

Urinary collagen peptides: Source of markers for bone metabolic processes in kidney transplant recipients

“…This method is based on the relative quantification of 29 internal collagen peptides of high abundance in human urine. In subsequent studies with large numbers of patient samples and covering a broad range of disease etiologies [31][32][33][34], this method has been demonstrated to be better suited than urinary creatinine specifically for comparative analysis of CE-MS peptide profiles. This remains true, even if some of the peptides used for calibration are affected by group differences.…”

Performances of acute kidney injury biomarkers vary according to sex

“…The cohort included in this study has been previously described (see Piedrafita et al . [ 8 ]). Patients referred for CBP surgery were prospectively recruited at the University Hospital of Toulouse (France) during two distinct time periods [March 2016–January 2017 ( n = 509) and January 2019–March 2020 ( n = 661)].…”

“…In this study, we took advantage of a large cohort of 1170 patients subjected to cardiac bypass (CBP) surgery to estimate and compare the incidence and risk factors of AKI in males and females as well as the performance of candidate AKI risk urinary biomarkers [neutrophil gelatinase-associated lipocalin (NGAL), [IGFBP7]·[TIMP-2] product (NephroCheck) and a unique 204 urinary peptides signature (AKI204)] [ 8 ] in this prototypic high-risk situation of AKI.…”

Publisher Correction to: A universal predictive and mechanistic urinary peptide signature in acute kidney injury

“…Following publication of the original article [ 1 ], the authors identified errors in the authorship which was caused by the publisher. Three of the collaborating authors were incorrectly listed as authors.…”

“…The authorship has been updated in this Publisher Correction article and the original article [ 1 ] has been corrected. The publisher apologises to the authors and readers for the inconvenience caused by these mistakes.…”