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<p>Sepsis-associated acute kidney injury (SA-AKI) portends severe health burden due to significant morbidity and mortality, while early diagnosis remains challenging. In this study, proximity-dependent barcoding assay (PBA) is established to profile the surface proteome of single urinary extracellular vesicle (uEV). Principle uEV clusters with unique function and origination are profiled in SA-AKI&#xa0;in a&#xa0;screening cohort. Complement receptor CD35 on single uEV (CD35-uEV) displays high diagnostic accuracy for SA-AKI (AUC-ROC 0.89&#xa0;in validation cohort, <i>n</i> = 134). Besides, CD35-uEV enables identification of subclinical AKI (AUC-ROC 0.84 in prospective cohort, <i>n</i> = 72). Moreover, CD35-uEV correlates closely with AKI severity which also predicts persistent AKI (AUC-ROC 0.77), mortality risks (AUC-ROC 0.70) and progression to AKD (AUC-ROC 0.66). Multi-omics profiling reveals that CD35-uEV are predominantly released from injured podocytes exhibiting diminished CD35 expression. Overall, this study identifies a single uEV biomarker related to injured podocyte for early diagnosis and risk stratification of SA-AKI.</p>

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Single urinary extracellular vesicle proteomics identifies complement receptor CD35 as a biomarker for sepsis-associated acute kidney injury

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年7月29日

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  • Ning Li,
  • Tao-Tao Tang,
  • Menglei Gu,
  • Yu-Qi Fu,
  • Wei-Wei Qian,
  • Nan Nan Ma,
  • An-Ran Shen,
  • Tingting Zhu,
  • Run-Bo Huo,
  • Tao Zhang,
  • Jian-Feng Xie,
  • Lu Zhang,
  • Bi-Cheng Liu,
  • Lin-Li Lv

摘要

Sepsis-associated acute kidney injury (SA-AKI) portends severe health burden due to significant morbidity and mortality, while early diagnosis remains challenging. In this study, proximity-dependent barcoding assay (PBA) is established to profile the surface proteome of single urinary extracellular vesicle (uEV). Principle uEV clusters with unique function and origination are profiled in SA-AKI in a screening cohort. Complement receptor CD35 on single uEV (CD35-uEV) displays high diagnostic accuracy for SA-AKI (AUC-ROC 0.89 in validation cohort, n = 134). Besides, CD35-uEV enables identification of subclinical AKI (AUC-ROC 0.84 in prospective cohort, n = 72). Moreover, CD35-uEV correlates closely with AKI severity which also predicts persistent AKI (AUC-ROC 0.77), mortality risks (AUC-ROC 0.70) and progression to AKD (AUC-ROC 0.66). Multi-omics profiling reveals that CD35-uEV are predominantly released from injured podocytes exhibiting diminished CD35 expression. Overall, this study identifies a single uEV biomarker related to injured podocyte for early diagnosis and risk stratification of SA-AKI.