Nephrology, Dialysis and Transplantation Unit, IRCCS Istituto Giannina Gaslini, Genoa, Italy.
Translational Transplant Research Center and Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Am J Transplant. 2024 Apr;24(4):688-692. doi: 10.1016/j.ajt.2023.12.010. Epub 2023 Dec 14.
Focal segmental glomerulosclerosis (FSGS) is one of the leading causes of kidney failure and it is characterized by a high rate of recurrence after kidney transplant. Moreover, FSGS recurrence is worsened by an increased risk of graft failure. Common therapies for FSGS recurrence mostly consist of plasma exchange treatments, also for prolonged time, and rituximab, with variable efficacy. We report 5 cases of early FSGS recurrence after kidney transplant, resistant to plasma exchange and rituximab treatment that subsequently resolved after combined therapy with rituximab and daratumumab. All cases were negative for genetic FSGS. The combined treatment induced a complete response in all the cases and was well tolerated. We also performed a comprehensive flow cytometry analysis in 2 subjects that may suggest a mechanistic link between plasma cells and disease activity. In conclusion, given the lack of viable treatments for recurrent FSGS, our reports support the rationale for a pilot trial testing the safety/efficacy profile of combined rituximab and daratumumab in posttransplant FSGS recurrence.
局灶节段性肾小球硬化症 (FSGS) 是导致肾衰竭的主要原因之一,其特征是肾移植后复发率很高。此外,FSGS 复发会增加移植物失功的风险。FSGS 复发的常见治疗方法主要包括血浆置换治疗,也需要长时间进行,以及利妥昔单抗,但疗效不一。我们报告了 5 例肾移植后早期 FSGS 复发的病例,这些病例对血浆置换和利妥昔单抗治疗有抗药性,随后联合使用利妥昔单抗和达雷妥尤单抗治疗后得到缓解。所有病例均未检出 FSGS 的遗传因素。联合治疗使所有病例均获得完全缓解,且耐受性良好。我们还对 2 名患者进行了全面的流式细胞术分析,这可能提示浆细胞与疾病活动之间存在机制联系。总之,鉴于复发性 FSGS 缺乏可行的治疗方法,我们的报告支持在移植后 FSGS 复发中测试联合使用利妥昔单抗和达雷妥尤单抗的安全性/疗效特征的试验。