Okada Shinri, Nishikubo Masashi, Shimomura Yoshimitsu, Hiramoto Nobuhiro, Osaki Keisuke, Hara Shigeo, Kondo Tadakazu, Ishikawa Takayuki
Department of Hematology, Kobe City Medical Center General Hospital, 2-1-1, Minatojima-Minamimachi, Chuo-ku, Kobe, 650-0047, Japan.
Department of Nephrology, Kobe City Medical Center General Hospital, 2-1-1, Minatojima-Minamimachi, Chuo-ku, Kobe, 650-0047, Japan.
Int J Hematol. 2025 Apr;121(4):553-559. doi: 10.1007/s12185-025-03930-4. Epub 2025 Jan 30.
Transplantation-associated thrombotic microangiopathy (TMA) is a severe complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT) with high mortality. As calcineurin inhibitors (CNIs) reportedly contribute to TMA via drug-induced endothelial injury, treatment of TMA often involves CNI discontinuation or dose reduction. However, renal-limited TMA, defined as biopsy-proven renal TMA without the classical triad (hemolytic anemia, thrombocytopenia, and organ damage), has rarely been reported after allo-HSCT, and its optimal management remains unknown. Herein, we report three cases of renal-limited TMA after allo-HSCT that presented with nephrotic syndrome, in which renal biopsy showed TMA and concurrent membranous nephropathy. All patients were refractory to glucocorticoid monotherapy and the addition of CNIs led to complete remission of nephrotic syndrome. Renal-limited TMA after allo-HSCT may present as nephrotic syndrome with distinct pathophysiological features from renal-limited TMA in non-allo-HSCT recipients. Previous reports have suggested that renal-limited TMA after allo-HSCT is associated with renal graft-versus-host disease, and thus optimizing immunosuppressive therapy, including CNI treatment, may be useful. CNI treatment may be an option even in the presence of renal-limited TMA after allo-HSCT accompanied by concurrent membranous nephropathy.
移植相关血栓性微血管病（TMA）是异基因造血干细胞移植（allo-HSCT）的一种严重并发症，死亡率很高。据报道，钙调神经磷酸酶抑制剂（CNI）通过药物诱导的内皮损伤导致TMA，因此TMA的治疗通常包括停用CNI或减少剂量。然而，肾局限性TMA，定义为经活检证实的肾TMA，无典型三联征（溶血性贫血、血小板减少和器官损伤），在allo-HSCT后很少见报道，其最佳治疗方法仍不清楚。在此，我们报告3例allo-HSCT后出现肾病综合征的肾局限性TMA病例，肾活检显示TMA并伴有膜性肾病。所有患者对糖皮质激素单药治疗均无效，加用CNI后肾病综合征完全缓解。allo-HSCT后的肾局限性TMA可能表现为肾病综合征，其病理生理特征与非allo-HSCT受者的肾局限性TMA不同。既往报道提示allo-HSCT后的肾局限性TMA与肾移植物抗宿主病有关，因此优化免疫抑制治疗，包括CNI治疗，可能是有用的。即使在allo-HSCT后出现肾局限性TMA并伴有膜性肾病的情况下，CNI治疗也可能是一种选择。
