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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.
In March 2024, health problems caused by supplements derived from red yeast rice manufactured by Kobayashi Pharmaceutical Co., Ltd was reported. As of November 24, 2024, a total of 2,628 individuals had visited medical facilities, and 397 deaths had been recorded. In Japan, this incident has developed into a social issue regarding the safety of dietary supplements. Even among patients who recovered, many were reported to have persistent partial renal impairment. Many aspects remain unclear; therefore, we consider that further investigation, including basic experimental studies, is needed.
We established the model of Choleste-Help / puberulic acid nephropathy with mice, primary human renal proximal tubular epithelial cells (hRPTECs) and hRPTEC-derived tubular organoids, then analyzed them using various approaches, including RNA-seq, extracellular flux analysis, and flow cytometry.
We established a mouse model of Choleste-Help/puberulic acid-induced nephropathy. Wild-type B6 mice were orally administered 1,000 mg/kgBW of the toxic lot of Choleste-Help once daily for six days and sacrificed on day 7. Compared with controls, mice treated with the toxic lot showed renal dysfunction on blood tests, as well as albuminuria and glycosuria on urinalysis. Histopathological sections revealed tubular injury similar to that observed in humans, with fibrosis confirmed by Masson’s trichrome and Picro-Sirius Red staining. In contrast, interstitial inflammatory cell infiltration and glomerular damage were not prominent. Intraperitoneal administration of 1 mg/kgBW of puberulic acid induced nephropathy as well. Transcriptome analysis revealed that kidneys from mice treated with either the toxic lot of Choleste-Help or puberulic acid displayed highly similar RNA expression profiles, consistent with puberulic acid being the causative substance. Pathway analysis further suggested that these RNA patterns indicated markedly impaired mitochondrial function in the kidney.
We next examined whether this phenomenon was reproducible in hRPTECs. Puberulic acid induced cell death in hRPTECs (EC50 = 66.04 μM, approximately twice as potent as cisplatin), predominantly through necrosis. In hRPTEC-derived tubular organoids, we found that repeated exposure at 5 μM, a concentration that is commonly attainable in humans, induced cellular injury.
To demonstrate that mitochondrial dysfunction precedes cell death, experiments with shorter exposure durations were performed. In cells treated for shorter durations, we observed mitochondrial membrane depolarization, decreased ATP levels, increased mitochondrial ROS, and reduced maximal respiration and spare respiratory capacity, indicating mitochondrial dysfunction caused by respiratory metabolism impairment.
We demonstrated that puberulic acid-induced mitochondrial dysfunction contributes to proximal tubular epithelial injury in Choleste-Help/puberulic acid nephropathy. On the other hand, damage to other organs rich in mitochondria has not been reported in humans, highlighting the need for further investigation into uptake pathways and organ specificity. (The content of this abstract was also presented at the 2025 ASN Kidney Week.)
