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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.
Patients with polycystic kidney disease (PKD) have build-up of large fluid-filled cysts on their kidneys. The growth of the cysts eventually causes a reduction in kidney function and the need for kidney replacement therapy. Patients also have hypertension and are therefore at risk of dying form a cardiovascular event. The exact cause of cyst progression is not known, however the immune system, especially macrophages, are known to play a role. The NLRP3 inflammasome is found within macrophages, and in other models of kidney disease, inhibition of NLRP3 can decrease cardiovascular and inflammatory burden. Therefore the aim of this study was to determine if the NLRP3 inflammasome contributes to PKD progression, and if treatment with an NLRP3 inhibitor (MCC950) can reduce cardiovascular burden, cyst growth and fibrosis.
Lewis Polycystic Kidney (LPK) rats and wild-type (WT) littermates, received an intervention of either MCC950 (20 mg/kg, daily SC injections) or placebo from 6 to 16 weeks of age (n=15-16 per group, both sexes). Blood pressure (BP) was measured by tail cuff, and kidney function assessed by serum biochemistry. Kidney histopathology was evaluated for cystic burden and collagen localisation. Inflammasome components and collagen amount were quantified via qPCR and activated NLRP3 was determined by immunohistochemistry.
From 6 weeks of age, LPKs were hypertensive, which persisted throughout the experiment (6 weeks: 180.2 mmHg LPK vs 148.5 mmHg WT, P<0.001; 16 weeks: 200.6 mmHg LPK vs 138.2 mmHg WT, P<0.001). At 16 weeks of age, LPKs had impaired kidney function (P<0.001), increased kidney, heart and spleen weight (P<0.001) with numerous cysts and collagen deposition in kidneys (P<0.001). Gene expression of NLRP3 inflammasome components (NLRP3, ASC, pro-caspase-1), downstream pro-inflammatory cytokines, interleukin (IL)-1β and IL-18, and fibrosis genes (collagen I, III and VI) were all increased in LPKs (P<0.05). In LPKs, immunofluorescent microscopy demonstration the formation of ASC specs, specifically in the cystic epithelium. Intervention with the inflammasome inhibitor, MCC950, reduced collagen I, III and IV gene expression in LPKs (P<0.05), which was supported by histological semi-quantification of fibrosis using picrosirius red staining (P<0.05). MCC950 also decreased gene expression of pro-caspase-1, pro-IL- 1β and pro-IL-18 in LPKs (P<0.05). However, MCC950 did not protect LPKs from increases in BP, cyst number or size, nor did treatment preserve kidney function at endpoint. Inflammasome components NLRP3 and ASC were not reduced with MCC950.
The NLRP3 inflammasome is present in cystic kidneys of LPKs and not in WT, indicating that it may play a role is disease progression. Intervention with MCC950 reduced collagen content in LPKs suggesting, NLRP3 may play a role in promoting collagen production. However, MCC950 did not improve hypertension, kidney function, or cystic burden. This suggests that there may be a complex interplay between NLRP3 and other inflammasomes that contribute to the pathology of PKD.
