#4359 LOSS OF GASDERMIN D LEADS TO AN EXACERBATION OF KIDNEY DAMAGE IN NEPHROCALCINOSIS-RELATED CHRONIC KIDNEY DISEASE

Abstract Background and Aims Gasdermin D (GSDMD) is a membrane-targeting pore-forming protein that primarily expressed in immune cells. In the proinflammatory cell death process known as pyroptosis, cleaved GSDMD plays crucial role through membrane pore formation, leading to release of cytokines rapture. Despite this, majority GSDMD's other physiological functions remain be elucidated. Previous reports have implicated pathogenesis kidney disease, utilizing some acute injury (AKI) animal models few chronic disease (CKD) models. However, it remains uncertain if contributes nephrocalcinosis-related CKD. Therefore, this study aimed investigate context. Method our study, 8-week-old GSDMD-knockout (KO) mice wildtype (WT) received an oxalate-rich diet (50 μmol/g sodium oxalate) for three weeks. All were sacrificed on day 21 kidneys harvested after sacrifice. Plasma urine samples collected at different time points before The glomerular filtration rate (GFR) was measured 0 20 assess excretion function. Histological analysis performed using Periodic Acid-Schiff (PAS) staining renal injury, Sirius Red check fibrosis, Pizzolato evaluate calcium crystal deposition, F4/80 infiltration macrophages, TUNEL death, RIPK3 phosphorylated MLKL (pMLKL) detecting necroptosis. And also examine expression kidney. Results showed no differences deposition between WT KO mice. GFR decreased both (day WT: 199.5±40.1 μl/min vs 175.0±44.8 μl/min, 156.5±37.9 KO: 73.0±48.1 μl/min), ΔGFR much greater (WT: −22.4±26.5% −59.4±19.3%). level blood urea nitrogen significantly higher 41.9±3.90 mg/dl 58.7±22.5 mg/dl) accordance with result GFR. PAS revealed more severe mice, indicated degree fibrosis Furthermore, macrophages Although significant positive cells KO, areas implicating necroptosis pMLKL staining. injured tubular during phase express (Fig. 1). vitro experiments, we evaluated functionality such phagocytic ability migratory bone marrow-derived (BMDMs), but didn't find any disparities BMDMs from those Conclusion Genetic deletion resulted macrophage Our results suggest potential especially GSDMD, contributing necroptosis, downstream calcium-oxalate formation progression CKD, similar previous mouse AKI.