肿瘤细胞治疗研究
英文原题：Collapsing Glomerulopathy and Thrombotic Microangiopathy after Chimeric Antigen Receptor T Cell Therapy.
Collapsing Glomerulopathy and Thrombotic Microangiopathy after Chimeric Antigen Receptor T Cell Therapy.
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CAR-T 细胞治疗在血液系统恶性肿瘤中的应用日益广泛，但可能并发免疫介导的毒性，包括急性肾损伤，后者通常归因于血流动力学因素或急性肾小管损伤。在此背景下，肾小球疾病极为罕见，文献中仅有零星病例报告。我们报告一例 65 岁非裔美国男性复发性多发性骨髓瘤患者，在接受靶向 BCMA 的 CAR-T 治疗后，于细胞因子释放综合征和免疫效应细胞相关噬血细胞性淋巴组织细胞增生症综合征的背景下，发生 AKI 并伴有肾病范围蛋白尿。肾活检显示，塌陷性肾小球病与活检证实的血栓性微血管病共存，提示足细胞和内皮细胞联合损伤。该患者接受了支持治疗以及针对全身炎症的免疫调节治疗，结果肾功能改善，蛋白尿显著减少，同时肿瘤学缓解持续。CAR-T 治疗后若发现肾病范围蛋白尿或持续性肾功能障碍，应促使考虑免疫效应细胞相关肾小球病，并在适当情况下进行肾活检评估。
Chimeric antigen receptor T-cell (CAR-T) therapy is increasingly used in hematologic malignancies but can be complicated by immune-mediated toxicities, including acute kidney injury, which is typically attributed to hemodynamic factors or acute tubular injury. Glomerular diseases in this setting are exceedingly rare, with only isolated case reports in the literature.
We report a 65-year-old African American man with relapsed multiple myeloma who developed AKI with nephrotic-range proteinuria following BCMA-directed CAR-T therapy, in the context of cytokine release syndrome and immune effector cell-associated hemophagocytic lymphohistiocytosis syndrome. Kidney biopsy demonstrated, the coexistence of collapsing glomerulopathy and biopsy-proven thrombotic microangiopathy, suggesting combined podocyte and endothelial injury.
The patient was managed with supportive measures and immunomodulatory therapy targeting systemic inflammation, resulting in improvement in kidney function and significant reduction in proteinuria alongside a sustained oncologic response. Recognition of nephrotic-range proteinuria or persistent kidney dysfunction after CAR-T therapy should prompt consideration of immune effector cell-associated glomerulopathy and evaluation with kidney biopsy when appropriate.
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