Benoit Stefanie W, Khandelwal Pooja, Grimley Michael S
Division of Nephrology and Hypertension, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.
Division of Bone Marrow Transplantation and Immunodeficiency, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.
Pediatr Transplant. 2022 Jun;26(4):e14263. doi: 10.1111/petr.14263. Epub 2022 Mar 6.
Membranous nephropathy (MN) is the most common cause of glomerulopathy after hematopoietic cell transplantation (HCT), most often occurring in the setting of graft versus host disease (GVHD). Twenty percent of patients will fail to respond to standard therapy and may progress to end stage renal disease. Here we present the case of a pediatric patient who developed chronic oral GVHD more than one-year post-HCT, who subsequently developed nephrotic syndrome (anasarca, nephrotic range proteinuria, hypoalbuminemia) and had a renal biopsy consistent with MN. Treated with ibrutinib for her GVHD, and steroids, tacrolimus, and rituximab for her MN, she failed to achieve even partial remission of her kidney disease after 8 months. Due to steroid toxicity and 0% CD19 cells on lymphocyte subpopulation flow cytometry, the decision was made to trial plasma cell depletion therapy with daratumumab.
She received three doses of daratumumab at weeks 1, 4, and 17.
Her nephrotic syndrome resolved and her serum albumin was greater than 3.0 gm/dl by week 10. She was weaned off of both steroids and tacrolimus by week 16, at which time she had near-complete remission of her renal disease.
Daratumumab may be an important, novel therapeutic option for post-HCT MN patients who are not responsive to standard therapies.
膜性肾病（MN）是造血细胞移植（HCT）后最常见的肾小球病病因，最常发生于移植物抗宿主病（GVHD）的情况下。20%的患者对标准治疗无反应，可能进展为终末期肾病。在此，我们报告一例儿科患者，其在HCT后一年多出现慢性口腔GVHD，随后发展为肾病综合征（全身性水肿、肾病范围蛋白尿、低蛋白血症），肾活检结果符合MN。她接受依鲁替尼治疗GVHD，接受类固醇、他克莫司和利妥昔单抗治疗MN，但8个月后肾病甚至未达到部分缓解。由于类固醇毒性以及淋巴细胞亚群流式细胞术显示CD19细胞为0%，决定试用达雷妥尤单抗进行浆细胞清除治疗。
她在第1、4和17周接受了三剂达雷妥尤单抗。
到第10周时，她的肾病综合征得到缓解，血清白蛋白大于3.0 g/dl。到第16周时，她停用了类固醇和他克莫司，此时她的肾病接近完全缓解。
对于对标准治疗无反应的HCT后MN患者，达雷妥尤单抗可能是一种重要的新型治疗选择。
