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

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 and Lin-Li Lv ()
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Ning Li: Zhong Da Hospital
Tao-Tao Tang: Zhong Da Hospital
Menglei Gu: Jiangsu Province Hospital of Chinese Medicine
Yu-Qi Fu: Zhong Da Hospital
Wei-Wei Qian: The Second Affiliated Hospital of Anhui Medical University
Nan Nan Ma: The Second Affiliated Hospital of Anhui Medical University
An-Ran Shen: Zhong Da Hospital
Tingting Zhu: Zhong Da Hospital
Run-Bo Huo: Zhongda Hospital
Tao Zhang: The Second Affiliated Hospital of Anhui Medical University
Jian-Feng Xie: Zhongda Hospital
Lu Zhang: Jiangsu Province Hospital of Chinese Medicine
Bi-Cheng Liu: Zhong Da Hospital
Lin-Li Lv: Zhong Da Hospital

Nature Communications, 2025, vol. 16, issue 1, 1-18

Abstract: Abstract 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.

Date: 2025
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DOI: 10.1038/s41467-025-62229-4

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