Takeuchi Kazuhiro, Kawamura Sayumi, Wada Yukihiro, Sakamoto Emi, Kuno Hideaki, Sakurabayashi Shun, Motohashi Tomomi, Okawa Hiroyuki, Kawamura Naohiro, Naito Shokichi, Aoyama Togo, Shimizu Akira, Takeuchi Yasuo
Department of Nephrology, Kitasato University School of Medicine, Kanagawa, Japan.
Analytical Human Pathology, Nippon Medical School, Tokyo, Japan.
Case Rep Nephrol Dial. 2024 Jul 25;14(1):128-137. doi: 10.1159/000540258. eCollection 2024 Jan-Dec.
Drug-induced tubulointerstitial injury is a common cause of renal impairment. Since the mechanisms of drug-induced tubular injury are diverse, various treatment approaches are needed according to the pathogenesis. Renal biopsy is indispensable to determine not only the pathological diagnosis, but also the underlying mechanism, and to guide appropriate treatment. Most recently, one of the red yeast supplements has been widely highlighted as a novel cause of tubular damage, mainly in Japan and Asia. However, neither detailed pathological findings nor the mechanism of renal impairment has been sufficiently reported.
Two cases of renal impairment after taking red yeast supplement internally are presented. Both cases showed renal dysfunction with low uric acid, potassium, and phosphorus levels, characteristic features of Fanconi syndrome. The renal biopsy findings of both cases showed severe injury to the proximal tubules with mild inflammatory cell infiltration. The proximal tubules exhibited diffuse loss of the brush border, flattening, and tubular lumen dilation. Immunofluorescence showed no deposition of immunoglobulin and complement in the glomeruli and tubules. Electron microscopic findings indicated proximal tubular damage without crystal deposition. Moreover, immunohistochemistry using the proximal tubular marker CD10 and a marker for distal tubules including the loop of Henle, E-cadherin, collectively demonstrated that the focus of renal injury in both cases was mainly the proximal tubules.
The red yeast rice supplement itself, its metabolized product, or other unknown contaminant components might directly induce proximal tubulopathy rather than an allergic reaction-related tubulointerstitial nephritis.
药物性肾小管间质损伤是肾功能损害的常见原因。由于药物性肾小管损伤的机制多种多样,需要根据发病机制采取不同的治疗方法。肾活检不仅对于确定病理诊断、明确潜在机制不可或缺,还能指导恰当的治疗。最近,一种红曲补充剂作为肾小管损伤的新病因受到广泛关注,主要集中在日本和亚洲地区。然而,关于其详细的病理表现及肾功能损害机制的报道并不充分。
本文报告了两例内服红曲补充剂后出现肾功能损害的病例。两例均表现为肾功能不全,伴有尿酸、钾和磷水平降低,这是范科尼综合征的特征性表现。两例的肾活检结果均显示近端肾小管严重损伤,伴有轻度炎性细胞浸润。近端肾小管呈现刷状缘弥漫性缺失、变平以及管腔扩张。免疫荧光显示肾小球和肾小管内无免疫球蛋白和补体沉积。电镜检查结果表明近端肾小管损伤但无晶体沉积。此外,使用近端肾小管标志物CD10以及包括髓袢在内的远端肾小管标志物E-钙黏蛋白进行免疫组化检测,共同表明两例肾损伤的主要部位均为近端肾小管。
红曲补充剂本身、其代谢产物或其他未知的污染成分可能直接导致近端肾小管病变,而非过敏反应相关的肾小管间质性肾炎。