Single urinary extracellular vesicle proteomics identifies complement receptor CD35 as a biomarker for sepsis-associated acute kidney injury
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 extra...
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Nature Portfolio
2025-07-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-62229-4 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Ning Li |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-46da5a2623b645ec9315d29a1a4451da |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-46da5a2623b645ec9315d29a1a4451da2025-08-20T03:43:22ZengNature PortfolioNature Communications2041-17232025-07-0116111810.1038/s41467-025-62229-4Single urinary extracellular vesicle proteomics identifies complement receptor CD35 as a biomarker for sepsis-associated acute kidney injuryNing Li0Tao-Tao Tang1Menglei Gu2Yu-Qi Fu3Wei-Wei Qian4Nan Nan Ma5An-Ran Shen6Tingting Zhu7Run-Bo Huo8Tao Zhang9Jian-Feng Xie10Lu Zhang11Bi-Cheng Liu12Lin-Li Lv13Institute of Nephrology, Southeast University School of Medicine, Zhong Da HospitalInstitute of Nephrology, Southeast University School of Medicine, Zhong Da HospitalAffiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese MedicineInstitute of Nephrology, Southeast University School of Medicine, Zhong Da HospitalDepartment of Urology, The Second Affiliated Hospital of Anhui Medical UniversityDepartment of Urology, The Second Affiliated Hospital of Anhui Medical UniversityInstitute of Nephrology, Southeast University School of Medicine, Zhong Da HospitalInstitute of Nephrology, Southeast University School of Medicine, Zhong Da HospitalJiangsu Provincial Key Laboratory of Critical Care Medicine, Department of Critical Care Medicine, Southeast University School of Medicine, Zhongda HospitalDepartment of Urology, The Second Affiliated Hospital of Anhui Medical UniversityJiangsu Provincial Key Laboratory of Critical Care Medicine, Department of Critical Care Medicine, Southeast University School of Medicine, Zhongda HospitalAffiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese MedicineInstitute of Nephrology, Southeast University School of Medicine, Zhong Da HospitalInstitute of Nephrology, Southeast University School of Medicine, Zhong Da HospitalAbstract 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.https://doi.org/10.1038/s41467-025-62229-4 |
| spellingShingle | 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 Single urinary extracellular vesicle proteomics identifies complement receptor CD35 as a biomarker for sepsis-associated acute kidney injury Nature Communications |
| title | Single urinary extracellular vesicle proteomics identifies complement receptor CD35 as a biomarker for sepsis-associated acute kidney injury |
| title_full | Single urinary extracellular vesicle proteomics identifies complement receptor CD35 as a biomarker for sepsis-associated acute kidney injury |
| title_fullStr | Single urinary extracellular vesicle proteomics identifies complement receptor CD35 as a biomarker for sepsis-associated acute kidney injury |
| title_full_unstemmed | Single urinary extracellular vesicle proteomics identifies complement receptor CD35 as a biomarker for sepsis-associated acute kidney injury |
| title_short | Single urinary extracellular vesicle proteomics identifies complement receptor CD35 as a biomarker for sepsis-associated acute kidney injury |
| title_sort | single urinary extracellular vesicle proteomics identifies complement receptor cd35 as a biomarker for sepsis associated acute kidney injury |
| url | https://doi.org/10.1038/s41467-025-62229-4 |
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