Abstract: FR-PO0767
Nuclear Export Inhibitor Selinexor Improves Kidney Function in a Rat Model of FSGS
Session Information
- Glomerular Diseases: Cell Homeostasis and Novel Injury Mechanisms
November 07, 2025 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1401 Glomerular Diseases: Mechanisms, including Podocyte Biology
Authors
- Gao, Yingying, Division of Nephrology and Clinical Immunology, RWTH University Clinic, Aachen, Germany
- Hamed, Mohamed, Institute of Biochemistry and Molecular Cell Biology, Medical School, RWTH Aachen University, Aachen, Germany
- Martin, Ina V., Division of Nephrology and Clinical Immunology, RWTH University Clinic, Aachen, Germany
- Raffetseder, Ute, Division of Nephrology and Clinical Immunology, RWTH University Clinic, Aachen, Germany
- Liu, Xiyang, Division of Nephrology and Clinical Immunology, RWTH University Clinic, Aachen, Germany
- Leitz, Anna, Division of Nephrology and Clinical Immunology, RWTH University Clinic, Aachen, Germany
- Moeller, Marcus J., Division of Nephrology and Clinical Immunology, RWTH University Clinic, Aachen, Germany
- Stamellou, Eleni, Division of Nephrology and Clinical Immunology, RWTH University Clinic, Aachen, Germany
- Schulz, Angela, Department of Clinical Pharmacology and Toxicology, Charité-Universitätsmedizin, Berlin, Germany
- Kreutz, Reinhold, Department of Clinical Pharmacology and Toxicology, Charité-Universitätsmedizin, Berlin, Germany
- Floege, Jürgen, Division of Nephrology and Clinical Immunology, RWTH University Clinic, Aachen, Germany
- Kramann, Rafael, Division of Nephrology and Clinical Immunology, RWTH University Clinic, Aachen, Germany
- Antonin, Wolfram, Institute of Biochemistry and Molecular Cell Biology, Medical School, RWTH Aachen University, Aachen, Germany
- Ostendorf, Tammo, Division of Nephrology and Clinical Immunology, RWTH University Clinic, Aachen, Germany
Background
FSGS is primarily driven by podocyte damage. Nuclear pore complexes (NPCs) control the passage between cytoplasm and nucleoplasm. They mediate a highly selective bidirectional transport of proteins, RNAs and RNA-protein complexes, which results in a specific nuclear and cytoplasmic environment, essential for proper cell function. While NPCs normally disassemble and renew during mitosis, post-mitotic cells like podocytes lack this surveillance mechanism, which means there can be accumulation of defective NPCs. This study explores the therapeutic potential of selinexor (KPT-330), an XPO1 inhibitor targeting NPC function.
Methods
Compound screening was performed in vitro using HeLa cells with compartmentalization defects. The therapeutic effect of KPT-330 was subsequently tested in vivo in Munich Wistar Froemter (MWF) rats with spontaneous FSGS development. Ten-week-old male MWF rats received KPT-330 for 10 weeks and were monitored for anadditional 20 weeks.
Results
KPT-330, an XPO-1 inhibitor, restored NPC function in HeLa cells. Untreated MWF rats developed FSGS, with about 35% glomeruli showing glomerulosclerosis at week 40, along with reduced kidney function. KPT-330 improved kidney function, lowering serum creatinine and cystatin C in MWF rats. A reduction in glomerular area was also observed. However, other histopathological markers, such as glomerulosclerosis, podocyte density, and parietal epithelial cell activation, did not change significantly.
Conclusion
KPT-330 enhanced renal function in MWF rats with FSGS but was insufficient to halt the progression of histological damage.
Funding
- Government Support – Non-U.S.