Kolonko Aureliusz, Słabiak-Błaż Natalia, Karkoszka Henryk, Więcek Andrzej, Piecha Grzegorz
Department of Nephrology, Transplantation and Internal Medicine, Medical University of Silesia, 40-027 Katowice, Poland.
J Clin Med. 2020 Feb 15;9(2):529. doi: 10.3390/jcm9020529.
Proteasome inhibitor bortezomib has been used in the treatment of refractory cases of acute and chronic antibody-mediated rejection (AMR) in kidney transplant recipients. However, its efficacy and safety as a primary treatment for early AMR has been scarcely investigated. We herein present our preliminary experience with bortezomib- and plasmapheresis-based primary treatment for early AMR. Thirteen patients transplanted between October 2015 and September 2019 were treated (starting at median 19th post-transplant day) with bortezomib/plasmapheresis protocol for early biopsy-proven AMR. Twelve out of thirteen patients received 4 doses and one patient recieved 3 doses of bortezomib (1.3 mg/m per dose). In 11/13 patients, 4-7 concomitant plasmapheresis sessions were performed, with or without intravenous immunoglobulin (IVIG). Of note, rituximab was not used in all study patients. The kidney graft and patient survival were 100%. The mean 3-month estimated glomerular filtration rate (eGFR) was 55.3 (95%CI: 44.9-65.8) mL/min/1.73m, 8/13 patients completed 12-month follow-up with mean eGFR 60.4 (45.4-75.4) mL/min/1.73m, and 6/13 patients completed a 24-month follow-up period with mean eGFR 73.9 (56.7-91.1) mL/min/1.73m. Neutropenia < 1 G/L was observed in one patient, third or fourth grade thrombocytopenia in two patients, and eleven patients needed a blood transfusion (median: 2 units/patient). The mid-term results of a primary bortezomib-based treatment for kidney AMR showed its non-inferiority as compared to preceding regimens and acceptable safety. However, our data should be validated in a multicenter randomized trial.
蛋白酶体抑制剂硼替佐米已被用于治疗肾移植受者急性和慢性抗体介导排斥反应（AMR）的难治性病例。然而，其作为早期AMR一线治疗的疗效和安全性鲜有研究。我们在此介绍基于硼替佐米和血浆置换的早期AMR一线治疗的初步经验。2015年10月至2019年9月间移植的13例患者（移植后中位第19天开始）接受硼替佐米/血浆置换方案治疗早期活检证实的AMR。13例患者中有12例接受4剂硼替佐米，1例接受3剂硼替佐米（每剂1.3mg/m）。13例患者中有11例进行了4 - 7次血浆置换，伴或不伴静脉注射免疫球蛋白（IVIG）。值得注意的是，并非所有研究患者都使用了利妥昔单抗。肾移植和患者生存率均为100%。3个月时平均估计肾小球滤过率（eGFR）为55.3（95%CI：44.9 - 65.8）mL/min/1.73m²，13例患者中有8例完成12个月随访，平均eGFR为60.4（45.4 - 75.4）mL/min/1.73m²，13例患者中有6例完成24个月随访，平均eGFR为73.9（56.7 - 91.1）mL/min/1.73m²。1例患者出现中性粒细胞减少<1G/L，2例患者出现三或四级血小板减少，11例患者需要输血（中位：2单位/患者）。基于硼替佐米的肾AMR一线治疗的中期结果显示，与之前的治疗方案相比，其具有非劣效性且安全性可接受。然而，我们的数据应在多中心随机试验中得到验证。
