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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.
Enarodustat, a novel hypoxia-inducible factor–prolyl hydroxylase inhibitor (HIF-PHI), has shown efficacy in correcting anemia and improving iron parameters in clinical studies. However, its specific regulatory mechanisms on iron metabolism, particularly under iron-overload conditions, remain incompletely understood. This study aimed to investigate the effects and molecular mechanisms of enarodustat on iron metabolism in a rat model of chronic kidney disease (CKD)–related anemia with iron overload.
A rat model of CKD anemia with iron overload was established via 5/6 nephrectomy combined with intraperitoneal iron dextran administration. Rats were stratified into mild, moderate, and severe iron-overload groups based on iron dosage, and each was subdivided into four subgroups: model control (no treatment), enarodustat, roxadustat, and recombinant human erythropoietin (rHuEPO). The treatment group had the same erythropoietic effect. A sham-operated group (renal capsule dissection only) served as control, with 4 rats per group. After 6 weeks of intervention, blood was collected biweekly for hematologic and iron metabolism parameters. Tissues (liver, spleen, kidney, heart, femur, jejunum, brain, aorta) were harvested post-sacrifice for iron content measurement (atomic absorption spectrophotometry), Prussian blue staining, and quantitative analysis.
Iron deposition increased with overload severity, predominantly in hepatocytes and splenic sinus macrophages, with the following organ distribution: liver/spleen > small intestine > kidney > femur > heart. No iron staining was detected in brain or aortic tissues. The rHuEPO group exhibited significantly higher iron deposition across organs than the enarodustat and roxadustat groups (P < 0.01), particularly in moderate-to-severe overload (Figure 1). Hematologically, rHuEPO transiently increased hemoglobin under moderate iron overload, but levels declined under severe overload versus controls (P < 0.0001), indicating aggravated anemia. This was accompanied by elevated ferritin (P < 0.0001), transferrin saturation (TSAT) >50%, and increased serum hepcidin (P < 0.0001) (Figure 2). Enarodustat uniquely modulated iron metabolism: ferritin remained lower than in other groups (P < 0.01), serum iron showed a V-shaped trend (decreased in mild, increased in moderate-to-severe overload), total iron-binding capacity increased (P < 0.01), and TSAT and hepcidin decreased (P < 0.001) (Figure 3). Hepatic iron content rose with overload but was lower in enarodustat and roxadustat groups than with rHuEPO. However, hepatic hepcidin expression declined during moderate-to-severe overload. HE staining of liver tissue revealed substantial hemosiderin deposition, accompanied by marked inflammatory cell infiltration and hepatocyte necrosis; these pathological changes were consistently more severe in the rHuEPO group than in the enarodustat and roxadustat groups (Figure 4).
In conclusion, enarodustat ameliorates iron metabolism via multi-targeted mechanisms, including hepcidin reduction and enhanced iron transport, thereby mitigating tissue iron deposition. Conversely, rHuEPO may exacerbate anemia under iron overload. A non-classical hepcidin regulation pattern was also identified, warranting further investigation.
