Renal Transplant Research Laboratory, Renal Transplant Unit, Division of Nephrology, Department of Internal Medicine, School of Medical Sciences, University of Campinas (UNICAMP), Campinas, São Paulo, Brazil; Laboratory of Translational Immunology, Department of Internal Medicine, School of Medical Sciences, University of Campinas, (UNICAMP), Campinas, São Paulo, Brazil.
Renal Transplant Research Laboratory, Renal Transplant Unit, Division of Nephrology, Department of Internal Medicine, School of Medical Sciences, University of Campinas (UNICAMP), Campinas, São Paulo, Brazil; Laboratory of Translational Immunology, Department of Internal Medicine, School of Medical Sciences, University of Campinas, (UNICAMP), Campinas, São Paulo, Brazil.
Transplant Proc. 2022 Jun;54(5):1270-1277. doi: 10.1016/j.transproceed.2021.11.041. Epub 2022 Mar 11.
Membranous nephropathy (MN) is a rare autoimmune disease that can develop a persistent nephrotic syndrome and end-stage kidney disease, with a recurrence rate of 30% to 40% after kidney transplant.
Retrospective case series of membranous nephropathy observed in a cohort of kidney transplant recipients with donor-specific anti-human leukocyte antigen antibodies and biopsy-proven antibody-mediated rejection (AMR).
We report 4 cases of membranous nephropathy associated with AMR. MN was diagnosed 10 to 92 months posttransplant, associated with de novo donor-specific antibodies, specific to class I in 2 cases, and class II in another 2. All cases presented typical morphology of membranous nephropathy, with subepithelial deposits with spikes at electron microscopy. Immunostaining for immunoglobulin G4 was negative in all cases, and podocyte-expressed M-type phospholipase A2 receptor was detected in glomerular basement membrane of 3 cases. Biopsy specimens from patients with longer follow-up showed more intense microvascular inflammation and chronic injury markers, possibly because of subclinical immunologic injury. AMR therapy included immunoglobulin 2g/kg in 3 patients, isolated or associated with plasmapheresis. One patient was not treated because of an active disseminated infection. Two patients remain with functioning grafts and under antiproteinuric therapy. Two grafts were lost, 1 because of chronic failure and the other because of death secondary to infection. Despite treatment, donor-specific antibodies remain detectable in a 6-month follow-up.
De novo MN is a rare manifestation associated with AMR in kidney transplant recipients. The occurrence of podocyte-expressed M-type phospholipase A2 receptor in de novo MN suggests antibody-mediated activation, despite the use of maintenance immunosuppression.
膜性肾病（MN）是一种罕见的自身免疫性疾病，可发展为持续性肾病综合征和终末期肾病，肾移植后复发率为 30%至 40%。
回顾性病例系列研究，观察了一组伴有供体特异性抗人类白细胞抗原抗体和活检证实的抗体介导的排斥反应（AMR）的肾移植受者中的膜性肾病。
我们报告了 4 例与 AMR 相关的膜性肾病。MN 在移植后 10 至 92 个月诊断，与新出现的供体特异性抗体相关，其中 2 例为 I 类特异性，另 2 例为 II 类特异性。所有病例均表现为典型的膜性肾病形态，电子显微镜下可见上皮下沉积物呈刺状。所有病例的免疫球蛋白 G4 免疫染色均为阴性，3 例肾小球基底膜检测到足细胞表达的 M 型磷脂酶 A2 受体。随访时间较长的活检标本显示更强烈的微血管炎症和慢性损伤标志物，可能是由于亚临床免疫损伤。AMR 治疗包括 3 例患者的免疫球蛋白 2g/kg，单独或联合血浆置换。1 例患者因活动性播散性感染未接受治疗。2 例患者仍保留功能移植物并接受降蛋白尿治疗。2 例移植物丢失，1 例因慢性衰竭，另 1 例因感染继发死亡。尽管进行了治疗，但在 6 个月的随访中仍可检测到供体特异性抗体。
新出现的 MN 是肾移植受者中与 AMR 相关的罕见表现。尽管使用了维持性免疫抑制，新出现的 MN 中足细胞表达的 M 型磷脂酶 A2 受体的出现提示抗体介导的激活。
