Chancharoenthana Wiwat, Leelahavanichkul Asada, Ariyanon Wassawon, Vadcharavivad Somratai, Phumratanaprapin Weerapong
Tropical Nephrology Research Unit, Department of Clinical Tropical Medicine, Faculty of Tropical Medicine, Mahidol University, Bangkok 10400, Thailand.
Department of Microbiology, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand.
J Clin Med. 2021 Aug 31;10(17):3939. doi: 10.3390/jcm10173939.
Recurrent IgA nephropathy (IgAN) remains an important cause of allograft loss in renal transplantation. Due to the limited efficacy of corticosteroid in the treatment of recurrent glomerulonephritis, rituximab was used in kidney transplant (KT) recipients with severe recurrent IgAN. A retrospective cohort study was conducted between January 2015 and December 2020. Accordingly, there were 64 KT recipients with biopsy-proven recurrent IgAN with similar baseline characteristics that were treated with the conventional standard therapy alone (controls, = 43) or together with rituximab (cases, = 21). All of the recipients had glomerular endocapillary hypercellularity and proteinuria (>1 g/d) with creatinine clearance (CrCl) > 30 mL/min/1.73 m and well-controlled blood pressure using renin-angiotensin-aldosterone blockers. The treatment outcomes were renal allograft survival rate, proteinuria, and post-treatment allograft pathology. During 3.8 years of follow-up, the rituximab-based regimen rapidly decreased proteinuria within 12 months after rituximab administration and maintained renal allograft function-the primary endpoint-for approximately 3 years. There were eight recipients in the case group (38%), and none in the control group reached a complete remission (proteinuria < 250 mg/d) at 12 months after treatment. Notably, renal allograft histopathology from patients with rituximab-based regimen showed the less severe endocapillary hypercellularity despite the remaining strong IgA deposition. In conclusion, adjunctive treatment with rituximab potentially demonstrated favorable outcomes for treatment of recurrent severe IgAN post-KT as demonstrated by proteinuria reduction and renal allograft function in our cohort. Further in-depth mechanistic studies with the longer follow-up periods are recommended.
复发性IgA肾病(IgAN)仍然是肾移植中同种异体肾移植丢失的重要原因。由于皮质类固醇治疗复发性肾小球肾炎的疗效有限,利妥昔单抗被用于患有严重复发性IgAN的肾移植(KT)受者。在2015年1月至2020年12月期间进行了一项回顾性队列研究。相应地,有64例经活检证实为复发性IgA肾病的KT受者,其基线特征相似,分别接受单纯传统标准治疗(对照组,n = 43)或联合利妥昔单抗治疗(病例组,n = 21)。所有受者均有肾小球毛细血管内细胞增多和蛋白尿(>1 g/d),肌酐清除率(CrCl)> 30 mL/min/1.73 m²,且使用肾素-血管紧张素-醛固酮阻滞剂可良好控制血压。治疗结果为同种异体肾移植存活率、蛋白尿和治疗后同种异体肾移植病理。在3.8年的随访期间,基于利妥昔单抗的治疗方案在利妥昔单抗给药后12个月内迅速降低蛋白尿,并维持同种异体肾移植功能(主要终点)约3年。病例组有8名受者(38%)在治疗后12个月达到完全缓解(蛋白尿< 250 mg/d),而对照组无一人达到完全缓解。值得注意的是,尽管仍有强烈的IgA沉积,但基于利妥昔单抗治疗方案的患者的同种异体肾移植组织病理学显示毛细血管内细胞增多程度较轻。总之,正如我们队列中蛋白尿减少和同种异体肾移植功能所表明的那样,利妥昔单抗辅助治疗可能对治疗KT后复发性严重IgAN显示出良好的结果。建议进行更长随访期的进一步深入机制研究。