Nephrology Division, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
Nephrology Division, Inova Children's Hospital, Falls Church, Virginia, USA.
Pediatr Transplant. 2024 Aug;28(5):e14774. doi: 10.1111/petr.14774.
Antibody-mediated rejection is one of the most significant risk factors for allograft dysfunction and failure in children and adolescents with kidney transplants, yet optimal treatment remains unidentified. To date, there are mixed findings regarding the use of Bortezomib, a plasma cell apoptosis inducer, as an adjunct therapy in the treatment of antibody-mediated rejection.
In a retrospective single center study, we reviewed the efficacy and tolerability of bortezomib as adjunct therapy for treatment-refractory antibody-mediated rejection.
Six patients with a median age of 14.6 years (range 6.9-20.1 years) received bortezomib at a mean of 71 months (range 15-83 months) post-kidney transplant. Four patients experienced decline in estimated glomerular filtration rate (eGFR) from 4% to 42%. One patient started bortezomib while on hemodialysis and did not recover graft function, and another patient progressed to hemodialysis 6 months after receiving bortezomib. Although DSA did not completely resolve, there was a statistically significant decline in DSA MFI pre and 12-months post-BZ (p = .012, paired t-test) for the subjects who were not on dialysis at the time of bortezomib. Chronic Allograft Damage Index (CADI) score of ≥3 was seen in all six subjects at their biopsy prior to therapy. No adverse effects were reported.
Bortezomib was well tolerated and resulted in improvements in MFI of DSA among four pediatric subjects without allograft failure, although no effects were observed on eGFR trajectory. Further studies are needed to clarify whether earlier intervention with bortezomib could prevent renal failure progression.
抗体介导的排斥反应是儿童和青少年肾移植后移植物功能障碍和衰竭的最重要危险因素之一，但最佳治疗方法仍未确定。迄今为止，关于硼替佐米（一种浆细胞凋亡诱导剂）作为抗体介导排斥反应治疗的辅助治疗的使用存在混合结果。
在一项回顾性单中心研究中，我们回顾了硼替佐米作为治疗难治性抗体介导排斥反应的辅助治疗的疗效和耐受性。
六名中位年龄为 14.6 岁（范围 6.9-20.1 岁）的患者在肾移植后平均 71 个月（范围 15-83 个月）接受硼替佐米治疗。四名患者的估计肾小球滤过率（eGFR）从 4%下降到 42%。一名患者开始接受硼替佐米治疗时正在接受血液透析，未恢复移植物功能，另一名患者在接受硼替佐米治疗 6 个月后进展为血液透析。尽管 DSA 并未完全消退，但在未接受透析的患者中，硼替佐米治疗前和 12 个月时 DSA MFI 有统计学显著下降（p=0.012，配对 t 检验）。在接受治疗前的活检中，所有六名患者的慢性移植物损伤指数（CADI）评分均≥3。未报告不良反应。
硼替佐米耐受性良好，在未发生移植物衰竭的四名儿科患者中导致 DSA 的 MFI 改善，尽管对 eGFR 轨迹没有影响。需要进一步研究以明确早期使用硼替佐米是否可以预防肾功能衰竭进展。
