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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.
Ischemia-reperfusion injury (IRI) is a key pathophysiological process in acute kidney injury (AKI) and renal transplantation. While hypoxia-inducible factor (HIF) stabilizers have demonstrated reno-protective potential, their immunomodulatory effects remain unclear. This study investigated the interplay between HIF-1α stabilization and the expression of Natural Killer Group 2, D member (NKG2D) ligands in the context of renal IRI. These ligands include MHC Class I Polypeptide-Related Sequence A (MICA) in humans, and Retinoic Acid Early Transcript 1 (RAE-1) and Histocompatibility 60 (H60) in mice, which are stress-inducible molecules that activate cytotoxic immune responses.
MICA expression was evaluated in renal biopsies from patients with acute kidney injury (AKI), post-renal transplantation patients, and controls (n=6 per group). A murine renal ischemia-reperfusion injury (IRI) model was established, and mice were randomly divided into four groups (n=6 per group): (1) Sham-operated, (2) Sham + FG-4592, (3) Ischemia/Reperfusion (I/R), and (4) I/R + FG-4592. Mice received pretreatment with the HIF stabilizer FG-4592 (Roxadustat, 10 mg/kg) or vehicle (saline). Renal function and tubular injury were assessed, and protein and mRNA levels of NKG2D ligands (RAE-1 and H60 in mice) and HIF-1α were analyzed. In vitro, the expression of MICA and RAE-1 was assessed in HK-2 and mTEC cells following hypoxia/reoxygenation (H/R) injury, with or without FG-4592 (10 μM) pretreatment.
Immunohistochemistry (IHC) revealed a significant upregulation of MICA expression in the renal tubules of patients with AKI or following transplantation compared to controls. In a murine IRI model, H&E staining demonstrated that FG-4592 treatment attenuated the severe tubular damage observed at 24 hours post-I/R in saline-treated mice. While I/R itself promoted HIF expression, FG-4592 further upregulated HIF-1α protein levels, as confirmed by Western blot and IHC. Notably, FG-4592 treatment also enhanced both the protein and mRNA levels of the murine NKG2D ligands RAE-1 and H60 in I/R-injured kidneys compared to saline controls. Immunohistochemical analysis further showed that I/R significantly increased the positive staining area for these ligands, an effect that was further amplified by FG-4592. Consistent with these in vivo findings, hypoxia/reoxygenation (H/R) upregulated NKG2D ligands (MICA in HK-2 cells and RAE-1 in mTECs), with FG-4592–mediated HIF-1α stabilization producing a more pronounced upregulation.
HIF-1α stabilization by FG-4592 exerts dual effects in renal IRI. It provides renoprotection, yet concurrently upregulates NKG2D ligand expression across human and murine models, suggesting a novel immunomodulatory mechanism whereby HIF-targeting therapies may influence post-injury immune surveillance. These findings indicate that the potential long-term consequences of NKG2D ligand induction require further investigation in the clinical application of HIF stabilizers, particularly for AKI and transplant recipients.
