Pediatric Nephrology, Department of Women's and Children's Health, Padua University Hospital, Padua, Italy.
Laboratory of Immunopathology and Molecular Biology of the Kidney, Department of Women's and Children's Health, Padua University Hospital, Padua, Italy.
Hum Immunol. 2024 Sep;85(5):111088. doi: 10.1016/j.humimm.2024.111088. Epub 2024 Aug 14.
Chronic active antibody-mediated rejection is one of the leading causes of graft failure and traditional therapies have unclear efficacy. Recent studies suggested that Tocilizumab could stabilize renal function and improve microvascular inflammation. Here we report the outcomes of Tocilizumab therapy in 6 pediatric kidney transplant recipients with biopsy-proven chronic active antibody-mediated rejection resistant to standard treatments. All patients received monthly Tocilizumab infusions for 6 months and were monitored for renal function (creatinine, estimated glomerular filtration rate (eGFR), proteinuria) and Human Leukocyte Antigens (HLA) and non-HLA antibodies at baseline and 3 and 6 months after Tocilizumab initiation. For each patient, a follow-up biopsy was scheduled at the end of the treatment. Renal function did not show stabilization or improvement (mean eGFR 37 ml/min/1.73 m pre-Tocilizumab and 27 ml/min/1.73 m 3 months after-Tocilizumab) and proteinuria remained stable. Moreover, Tocilizumab had no impact on HLA and non-HLA antibodies. Graft loss was observed in 3 patients (50 %) and 4 patients who underwent post-treatment biopsy showed a worsening in overall chronicity scores. In our pediatric series, rescue therapy with Tocilizumab did not appear to be effective in modifying the natural history of chronic active antibody-mediated rejection.
慢性持续性抗体介导的排斥反应是移植物失功的主要原因之一，而传统疗法的疗效并不明确。最近的研究表明，托珠单抗可稳定肾功能并改善微血管炎症。在此，我们报告了 6 例经活检证实的慢性持续性抗体介导的排斥反应的儿科肾移植受者接受托珠单抗治疗的结果，这些受者对标准治疗具有耐药性。所有患者均接受每月托珠单抗输注 6 个月，并在基线、托珠单抗治疗开始后 3 个月和 6 个月监测肾功能（肌酐、估算肾小球滤过率（eGFR）、蛋白尿）和人类白细胞抗原（HLA）和非 HLA 抗体。每位患者在治疗结束时都安排了后续活检。肾功能未显示稳定或改善（托珠单抗治疗前平均 eGFR 为 37ml/min/1.73m，托珠单抗治疗 3 个月后为 27ml/min/1.73m），蛋白尿保持稳定。此外，托珠单抗对 HLA 和非 HLA 抗体没有影响。3 名患者（50%）发生移植物失功，4 名接受治疗后活检的患者整体慢性评分恶化。在我们的儿科系列研究中，托珠单抗的抢救治疗似乎并未有效改变慢性持续性抗体介导的排斥反应的自然病程。
