A nationwide questionnaire study evaluated kidney injury associated with Beni-koji tablets in Japan.

Red yeast rice, traditionally used in Asian cuisine and increasingly marketed as a dietary supplement for cholesterol management, has recently been linked to kidney dysfunction in Japan. In late 2023 to early 2024, multiple cases involving specific Beni-koji (red yeast rice) tablets from three different Beni-koji preparations, prompted a safety reevaluation. Although citrinin, a known nephrotoxin of red yeast rice, was not produced by the implicated strains, new safety concerns emerged. Here, we aimed to investigate the clinical, laboratory, and pathological features of affected patients with a two-phase nationwide survey of Japanese nephrologists. The initial survey captured clinical presentations, while the follow-up survey tracked changes in kidney function and gathered pathological data. Statistical analyses included trend assessments across estimated glomerular filtration rate (eGFR) categories and mixed-effects models for eGFR trajectories. Of 192 patients, 94.1% presented with low eGFR (under 60 ml/min/1.73m). Laboratory findings revealed characteristics of Fanconi syndrome, including hypokalemia, hypophosphatemia, hypouricemia, glycosuria, and metabolic acidosis. Creatine kinase levels were not elevated suggesting no rhabdomyolysis related kidney injury. Kidney biopsies showed predominant tubulointerstitial changes, with 50% exhibiting tubulointerstitial nephritis and 32% showing tubular necrosis. Glomerular changes were less prominent. Following product discontinuation and treatment, Fanconi syndrome-related parameters improved significantly. However, 87% of patients still had eGFR under 60 ml/min/1.73m at the last observation. Our findings underscore the need for long-term follow-up of affected individuals and highlight the importance of rigorous safety evaluations for dietary supplements. Further research is necessary to establish definitive causal relationships and long-term outcomes.