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During the congress, E-Posters will be accessible to all participants on the congress website 24/7, as well as in the E-poster stations in the congress center.
Preparing your E-Poster
Please review the E-Poster format requirements carefully when preparing your E-Poster. Should your E-Poster not meet the mentioned requirements, it may not be displayed as described above.
E-Poster Submission Deadline
Please prepare and upload your E-Poster no later than March 14, 2026 11.59PM CET. After this date, you will no longer be able to prepare and upload your E-poster and it will not be displayed and accessible on the congress website.
Please follow the instructions below to input your abstract title.
Abstract titles should be brief and reflect the content of the abstract.
Sunitinib, a small-molecular tyrosine kinase inhibitor (TKI), is widely used as a first-line treatment for multiple malignancies but is limited by nephrotoxicity, most notably proteinuria. Preventing and managing sunitinib-associated nephrotoxicity remains challenging due to incomplete understanding of its mechanisms.
We retrospectively analyzed clinical data from 141 patients with metastatic renal cell carcinoma (mRCC) treated with sunitinib. Serum ET-1 in both patients and murine models were measured by ELISA and correlated with proteinuria severity. In murine models of sunitinib-induced nephrotoxicity, single-cell RNA sequencing (scRNA-seq) was performed on kidney tissue. ET-1 and ETAR expression in kidney was examined by immunofluorescence, while flow cytometry assessed podocyte apoptosis, mitochondrial membrane potential, and oxidative stress. Podocyte metabolic activity was evaluated using a Seahorse X96 analyzer. Therapeutic experiments evaluated Atrasentan (ETAR antagonist) and Shikonin (PKM2 inhibitor) for 4 weeks, with renal pathology assessed by PAS staining and electron microscopy.
Serum analysis of 31 mRCC patients showed significant circulating ET-1 elevation following sunitinib therapy, with higher levels observed in those with severe proteinuria. Moreover, serum ET-1 levels were negatively correlated with eGFR. scRNA-seq identified crosstalk between glomerular endothelial cells (GEC) and podocytes via activation of the endothelin-1/endothelin A receptor (ET-1/ETAR) axis as a critical driver of sunitinib-induced nephrotoxicity. Mechanistically, GEC-derived ET-1 activated ETAR/β-arrestin-1 signaling in adjacent podocytes, promoting PKM2 dimerization and nuclear translocation, which in turn activated NF-κB signaling and oxidative stress. Pharmacological blockade of ETAR or inhibition of PKM2 attenuated podocyte injury and reduced proteinuria.
GEC-derived ET-1 promotes podocyte injury via ETAR/PKM2 signaling in sunitinib-induced nephrotoxicity.Targeting ET-1/ETAR signaling and PKM2-mediated glycolytic reprogramming may represent novel therapeutic strategies to mitigate sunitinib-associated nephrotoxicity, with potential implications for improving long-term renal outcomes in oncology care.
