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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.
Recent cases of acute kidney injury (AKI) in Japan have been associated with the intake of Beni-koji CholesteHelp supplements, in which puberulic acid has been identified as a potential nephrotoxic contaminant. To establish a reliable in vitro nephrotoxicity testing platform that reflects drug-induced renal injury, we developed a kidney organoid–based screening system derived from adult rat kidney stem (KS) cells. This study aimed to evaluate the nephrotoxicity of PA using this model and to validate the findings in a puberulic acid -induced mouse AKI model.
KS cells previously isolated from adult rat renal cortex were cultured in a 3D matrix to form kidney organoids that reproducibly developed proximal tubule-like structures expressing Aquaporin-1 and glomerulus-like domains. Organoids were exposed for 72 hrs to Beni-koji CholesteHelp (AKI-related lot), puberulic acid, or cisplatin as a positive control. H&E, immunohistochemical (cleaved caspase-3, COX-IV and oxidative stress markers (8-OHdG)), and transmission electron microscopy (TEM) analyses were performed, along with qPCR for KIM-1. C57BL/6N mice were intraperitoneally administered puberulic acid for two consecutive days, and renal function and histopathology were assessed on day 4.
KS cell-derived kidney organoids exhibited high reproducibility and tissue-like organization resembling native renal tubules. Cisplatin exposure caused epithelial cell shedding, and increased cleaved caspase-3-positive apoptotic cells. KIM-1 expression was significantly upregulated, confirming tubular injury. When treated with Beni-koji CholesteHelp or puberulic acid, organoids displayed acute tubular necrosis (ATN)-like changes, including cytoplasmic vacuolization and brush border disruption observed by TEM. PA exposure induced a marked increase in KIM-1 mRNA expression and apoptotic cells. TEM revealed mitochondrial swelling and cristae loss, and COX-IV expression was reduced, indicating mitochondrial dysfunction. Elevated 8-OHdG levels suggested oxidative DNA damage. In vivo, puberulic acid-treated mice showed renal impairment with elevated serum creatinine and urinary albumin/creatinine ratios. Histological analysis demonstrated tubular atrophy, epithelial desquamation, and cast formation without glomerular abnormalities, recapitulating the organoid findings. These results indicate that PA directly induces proximal tubular injury via mitochondrial dysfunction and oxidative stress, leading to apoptotic and necrotic cell death. These findings establish a direct experimental link between supplement-derived toxins and human-relevant renal injury, bridging clinical observation with mechanistic validation in vitro and in vivo.
We established a reproducible KS cell–derived kidney organoid system capable of detecting nephrotoxic responses and elucidating mechanisms such as oxidative stress and mitochondrial dysfunction. Using this platform, we identified puberulic acid as a direct nephrotoxin responsible for Beni-koji CholesteHelp-associated AKI. This study not only confirms the causal link between supplement-derived toxicants and AKI but also demonstrates the feasibility of organoid-based safety screening within regulatory New Approach Methodologies (NAMs) frameworks.
