Podocyte extracellular vesicles and immune mediators as urinary biomarkers in active lupus nephritis
Abstract Urinary extracellular vesicles (uEVs) and immune mediators have emerged as potential minimally invasive renal biomarkers. Even though active lupus nephritis (LN) is associated with immune complex deposition, tissue inflammation, and podocyte damage, it remains unclear how these parameters a...
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Nature Portfolio
2025-08-01
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| Online Access: | https://doi.org/10.1038/s41598-025-08236-3 |
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| author | Lilian Alves Ana Patrícia Lemos Jessyca Martins Suellen da Costa Fonseca Rodrigo Cutrim Gaudio Higor Lima Camila Carvalho Alice Ramos Gilmar de Souza Lacerda Pedro Barbosa da Fonseca Fernanda G. De Felice Mauro Jorge Cabral-Castro Jorge Paulo Strogoff de Matos Jorge Reis Almeida Dylan Burger Thalia Medeiros Andrea Alice Silva |
| author_facet | Lilian Alves Ana Patrícia Lemos Jessyca Martins Suellen da Costa Fonseca Rodrigo Cutrim Gaudio Higor Lima Camila Carvalho Alice Ramos Gilmar de Souza Lacerda Pedro Barbosa da Fonseca Fernanda G. De Felice Mauro Jorge Cabral-Castro Jorge Paulo Strogoff de Matos Jorge Reis Almeida Dylan Burger Thalia Medeiros Andrea Alice Silva |
| author_sort | Lilian Alves |
| collection | DOAJ |
| description | Abstract Urinary extracellular vesicles (uEVs) and immune mediators have emerged as potential minimally invasive renal biomarkers. Even though active lupus nephritis (LN) is associated with immune complex deposition, tissue inflammation, and podocyte damage, it remains unclear how these parameters are simultaneously altered in systemic lupus erythematosus (SLE). Thus, we aimed to evaluate uEVs as biomarkers in LN, in association with urinary immune mediators. In this cross-sectional study, uEVs were isolated from SLE patients and healthy donors by differential centrifugation and characterized and/or quantified by electron microscopy, nanoscale flow cytometry, and nanoparticle tracking analysis (NTA). Urinary immune mediators were assessed by a multiplex assay. We included 82 patients (42.6 ± 11.3 years-old, 91.4% female), of whom 56.1% (n = 46) had LN, and 18 healthy donors (37.5 ± 8.2 years-old, 83.3% female). No differences were found for particle size/concentration by NTA, but higher counts of total (P = 0.03) and podocyte-derived (P = 0.01) uEVs were observed in SLE patients, especially in active LN (P = 0.02; P = 0.03). We also identified higher urinary levels of cytokines such as IL-6, IL-8, and CCL-2 according to SLE activity and LN (P < 0.05). Significant correlations were observed between uEVs, immune mediators, R-SLEDAI-2K, proteinuria, and albuminuria in active LN. Lastly, the combinatory analysis of podocyte uEVs, IL-6, IFN-γ, IL-8, uCCL-2 and CCL-3 showed a good predictive power to detect active LN (AUC = 0.88, P = 0.0009). Our results suggest that urinary podocyte-derived uEVs and cytokines are associated with LN activity, which may reflect podocyte injury mediated by inflammation. Thus, the combined application of these biomarkers could help to identify patients with podocyte damage and renal inflammation. |
| format | Article |
| id | doaj-art-94bdcd8b861548d2a032bf4dacd23cbd |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Nature Portfolio |
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| spelling | doaj-art-94bdcd8b861548d2a032bf4dacd23cbd2025-08-20T03:42:28ZengNature PortfolioScientific Reports2045-23222025-08-0115111110.1038/s41598-025-08236-3Podocyte extracellular vesicles and immune mediators as urinary biomarkers in active lupus nephritisLilian Alves0Ana Patrícia Lemos1Jessyca Martins2Suellen da Costa Fonseca3Rodrigo Cutrim Gaudio4Higor Lima5Camila Carvalho6Alice Ramos7Gilmar de Souza Lacerda8Pedro Barbosa da Fonseca9Fernanda G. De Felice10Mauro Jorge Cabral-Castro11Jorge Paulo Strogoff de Matos12Jorge Reis Almeida13Dylan Burger14Thalia Medeiros15Andrea Alice Silva16Multiuser Laboratory for Research Support in Nephrology and Medical Sciences, Faculty of Medicine, Universidade Federal FluminenseMultiuser Laboratory for Research Support in Nephrology and Medical Sciences, Faculty of Medicine, Universidade Federal FluminenseMultiuser Laboratory for Research Support in Nephrology and Medical Sciences, Faculty of Medicine, Universidade Federal FluminenseMultiuser Laboratory for Research Support in Nephrology and Medical Sciences, Faculty of Medicine, Universidade Federal FluminenseRheumatology Unit, Hospital Universitário Antonio Pedro (HUAP/UFF)Multiuser Laboratory for Research Support in Nephrology and Medical Sciences, Faculty of Medicine, Universidade Federal FluminenseMultiuser Laboratory for Research Support in Nephrology and Medical Sciences, Faculty of Medicine, Universidade Federal FluminenseMultiuser Laboratory for Research Support in Nephrology and Medical Sciences, Faculty of Medicine, Universidade Federal FluminenseMultiuser Laboratory for Research Support in Nephrology and Medical Sciences, Faculty of Medicine, Universidade Federal FluminenseD’Or Institute for Research and EducationD’Or Institute for Research and EducationMultiuser Laboratory for Research Support in Nephrology and Medical Sciences, Faculty of Medicine, Universidade Federal FluminenseDepartment of Clinical Medicine, Faculty of Medicine, Universidade Federal FluminenseMultiuser Laboratory for Research Support in Nephrology and Medical Sciences, Faculty of Medicine, Universidade Federal FluminenseKidney Research Centre, Inflammation and Chronic Disease Program, The Ottawa Hospital Research InstituteMultiuser Laboratory for Research Support in Nephrology and Medical Sciences, Faculty of Medicine, Universidade Federal FluminenseMultiuser Laboratory for Research Support in Nephrology and Medical Sciences, Faculty of Medicine, Universidade Federal FluminenseAbstract Urinary extracellular vesicles (uEVs) and immune mediators have emerged as potential minimally invasive renal biomarkers. Even though active lupus nephritis (LN) is associated with immune complex deposition, tissue inflammation, and podocyte damage, it remains unclear how these parameters are simultaneously altered in systemic lupus erythematosus (SLE). Thus, we aimed to evaluate uEVs as biomarkers in LN, in association with urinary immune mediators. In this cross-sectional study, uEVs were isolated from SLE patients and healthy donors by differential centrifugation and characterized and/or quantified by electron microscopy, nanoscale flow cytometry, and nanoparticle tracking analysis (NTA). Urinary immune mediators were assessed by a multiplex assay. We included 82 patients (42.6 ± 11.3 years-old, 91.4% female), of whom 56.1% (n = 46) had LN, and 18 healthy donors (37.5 ± 8.2 years-old, 83.3% female). No differences were found for particle size/concentration by NTA, but higher counts of total (P = 0.03) and podocyte-derived (P = 0.01) uEVs were observed in SLE patients, especially in active LN (P = 0.02; P = 0.03). We also identified higher urinary levels of cytokines such as IL-6, IL-8, and CCL-2 according to SLE activity and LN (P < 0.05). Significant correlations were observed between uEVs, immune mediators, R-SLEDAI-2K, proteinuria, and albuminuria in active LN. Lastly, the combinatory analysis of podocyte uEVs, IL-6, IFN-γ, IL-8, uCCL-2 and CCL-3 showed a good predictive power to detect active LN (AUC = 0.88, P = 0.0009). Our results suggest that urinary podocyte-derived uEVs and cytokines are associated with LN activity, which may reflect podocyte injury mediated by inflammation. Thus, the combined application of these biomarkers could help to identify patients with podocyte damage and renal inflammation.https://doi.org/10.1038/s41598-025-08236-3Lupus nephritisPodocyteExtracellular vesiclesUrineImmune mediators |
| spellingShingle | Lilian Alves Ana Patrícia Lemos Jessyca Martins Suellen da Costa Fonseca Rodrigo Cutrim Gaudio Higor Lima Camila Carvalho Alice Ramos Gilmar de Souza Lacerda Pedro Barbosa da Fonseca Fernanda G. De Felice Mauro Jorge Cabral-Castro Jorge Paulo Strogoff de Matos Jorge Reis Almeida Dylan Burger Thalia Medeiros Andrea Alice Silva Podocyte extracellular vesicles and immune mediators as urinary biomarkers in active lupus nephritis Scientific Reports Lupus nephritis Podocyte Extracellular vesicles Urine Immune mediators |
| title | Podocyte extracellular vesicles and immune mediators as urinary biomarkers in active lupus nephritis |
| title_full | Podocyte extracellular vesicles and immune mediators as urinary biomarkers in active lupus nephritis |
| title_fullStr | Podocyte extracellular vesicles and immune mediators as urinary biomarkers in active lupus nephritis |
| title_full_unstemmed | Podocyte extracellular vesicles and immune mediators as urinary biomarkers in active lupus nephritis |
| title_short | Podocyte extracellular vesicles and immune mediators as urinary biomarkers in active lupus nephritis |
| title_sort | podocyte extracellular vesicles and immune mediators as urinary biomarkers in active lupus nephritis |
| topic | Lupus nephritis Podocyte Extracellular vesicles Urine Immune mediators |
| url | https://doi.org/10.1038/s41598-025-08236-3 |
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