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DC Field | Value | Language |
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dc.contributor.author | Martinez Valenzuela, Laura | - |
dc.contributor.author | Gómez-preciado, Francisco | - |
dc.contributor.author | Guiteras, Jordi | - |
dc.contributor.author | Antón Pampols, Paula | - |
dc.contributor.author | Gomà, Montserrat | - |
dc.contributor.author | Fulladosa, Xavier | - |
dc.contributor.author | Cruzado, Josep Maria | - |
dc.contributor.author | Torras, Joan | - |
dc.contributor.author | Draibe, Juliana | - |
dc.date.accessioned | 2024-07-02T15:23:44Z | - |
dc.date.available | 2024-07-02T15:23:44Z | - |
dc.date.issued | 2024-05-03 | - |
dc.identifier.uri | http://hdl.handle.net/2445/214206 | - |
dc.description.abstract | Introduction Immune checkpoint inhibitors (ICIs) induce acute interstitial nephritis (AIN) in 2-5% of patients, with a clearly higher incidence when they are combined with platinum derivatives. Unfortunately, suitable disease models and non-invasive biomarkers are lacking. To fill this gap in our understanding, we investigated the renal effects of cisplatin and anti-PD-L1 antibodies in mice, assessing PD-1 renal expression and cytokine levels in mice with AIN, and then we compared these findings with those in AIN-diagnosed cancer patients.Methods Twenty C57BL6J mice received 200 mu g of anti-PD-L1 antibody and 5 mg/kg cisplatin intraperitoneally and were compared with those receiving cisplatin (n = 6), anti-PD-L1 (n = 7), or saline (n = 6). After 7 days, the mice were euthanized. Serum and urinary concentrations of TNF alpha, CXCL10, IL-6, and MCP-1 were measured by Luminex. The kidney sections were stained to determine PD-1 tissue expression. Thirty-nine cancer patients with AKI were enrolled (AIN n = 33, acute tubular necrosis (ATN) n = 6), urine MCP-1 (uMCP-1) was measured, and kidney sections were stained to assess PD-1 expression.Results Cisplatin and anti PD-L1 treatment led to 40% AIN development (p = 0.03) in mice, accompanied by elevated serum creatinine and uMCP1. AIN-diagnosed cancer patients also had higher uMCP1 levels than ATN-diagnosed patients, confirming our previous findings. Mice with AIN exhibited interstitial PD-1 staining and stronger glomerular PD-1 expression, especially with combination treatment. Conversely, human AIN patients only showed interstitial PD-1 positivity.Conclusions Only mice receiving cisplatin and anti-PDL1 concomitantly developed AIN, accompanied with a more severe kidney injury. AIN induced by this drug combination was linked to elevated uMCP1, consistently with human AIN, suggesting that uMCP1 can be potentially used as an AIN biomarker. | - |
dc.format.mimetype | application/pdf | - |
dc.language.iso | eng | - |
dc.publisher | Springer Science and Business Media LLC | - |
dc.relation.isformatof | Reproducció del document publicat a: https://doi.org/10.1186/s12967-024-05177-9 | - |
dc.relation.ispartof | Journal of Translational Medicine, 2024, vol. 22, issue. 1 | - |
dc.relation.uri | https://doi.org/10.1186/s12967-024-05177-9 | - |
dc.source | Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL)) | - |
dc.title | Immune checkpoint inhibitors induce acute interstitial nephritis in mice with increased urinary MCP1 and PD-1 glomerular expression | - |
dc.type | info:eu-repo/semantics/article | - |
dc.date.updated | 2024-06-20T10:15:08Z | - |
dc.rights.accessRights | info:eu-repo/semantics/embargoedAccess | - |
Appears in Collections: | Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL)) |
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File | Description | Size | Format | |
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s12967-024-05177-9.pdf | 3.17 MB | Adobe PDF | View/Open |
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