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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.
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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.
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Abstract titles should be brief and reflect the content of the abstract.
Alport syndrome is a hereditary kidney disorder caused by mutations in type IV collagen genes. These mutations lead to structural abnormalities in the glomerular basement membrane, resulting in proteinuria, glomerulosclerosis, and progressive renal dysfunction, ultimately leading to chronic kidney disease (CKD). Although Col4a3 and Col4a5 knockout mice have been reported as models of Alport syndrome, they do not fully reflect the mutation-driven nature of the human disease, limiting clinical relevance. To address this, we generated a mouse model carrying the human Alport-associated Col4a5 R471* mutation. While angiotensin receptor blockers (ARBs) offer clinical benefit, they are not curative, highlighting the need for new therapeutic strategies. Roflumilast, a phosphodiesterase 4 (PDE4) inhibitor, has been reported to ameliorate diabetic nephropathy in a mouse model, sharing common pathological features with Alport syndrome (such as proteinuria, progressive inflammation and fibrosis of the kidney). In this study, we examined whether the Col4a5 mutant mouse replicates key pathological features of Alport syndrome and CKD, and whether the therapeutic effects of ARBs, such as irbesartan, observed in patients are similarly reproduced. We also investigated the potential of roflumilast as a treatment option in this model.
Col4a5 mutant mice at 11 weeks of age were treated with irbesartan or roflumilast for 8 weeks. Urinary albumin levels were monitored over time, and renal histology, gene expression, and cAMP levels were assessed at the study endpoint.
The Col4a5 R471* mutation recapitulated patient-like phenotypes, including an elevated urinary albumin-to-creatinine ratio (UACR) and increased expression of pro-fibrotic and pro-inflammatory genes. Treatment with irbesartan significantly attenuated these changes, indicating that the Col4a5 R471* mutant model responds to a clinically established ARB therapy. In the kidneys of Col4a5 R471* mutant mice, mRNA expression of PDE4 isoforms (PDE4A–D) was markedly upregulated. Roflumilast treatment significantly increased plasma and renal cAMP levels, confirming its pharmacodynamic activity, and moderately reduced the expression of fibrotic markers. However, roflumilast did not clearly ameliorate proteinuria or inflammatory responses.
The Col4a5 R471* mutant mouse not only recapitulates key pathological features of Alport syndrome but also demonstrates responsiveness to irbesartan, underscoring its translational relevance for drug evaluation in Alport syndrome and CKD. Irbesartan exerted broad renoprotective effects, whereas roflumilast showed only limited impact on overall disease progression. These findings suggest that PDE4 inhibition alone is insufficient to confer renoprotection in Alport syndrome; however, it may hold potential as an adjunctive strategy when combined with renin–angiotensin system blockade.
