A case report of adrenocorticotropic hormone to treat recurrent focal segmental glomerular sclerosis post-transplantation and biomarker monitoring.
A case report of adrenocorticotropic hormone to treat recurrent focal segmental glomerular sclerosis post-transplantation and biomarker monitoring.
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DOI：
10.3389/fmed.2015.00013
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发表时间：
2015
影响因子：
3.9
通讯作者：
Brennan DC
中科院分区：
文献类型：
--
作者：
Anwar S;Larson DS;Naimi N;Ashraf M;Culiberk N;Liapis H;Wei C;Reiser J;Brennan DC
背景资料：肾移植受者的复发性局灶节段性肾小球硬化（rFSGS）是一种难以预测和治疗的疾病，早期的rFSGS可能是由循环因子和抗体引起的。研究方法：我们报告一例23岁的白色男性患者，在1个单倍型匹配的活体相关移植后9个月出现rFSGS和急性肾功能衰竭，需要透析。我们回顾性分析了来自不同临床阶段的血清样本的rFSGS生物标志物：血清肾小球白蛋白通透性（Palb）、可溶性尿激酶型纤溶酶原激活物受体（suPAR）血清水平以及人足细胞上的suPAR-β3整合素信号传导和血管紧张素II I型受体抗体（AT 1 R-Ab）滴度。结果：在开始透析前移植前1年和移植时，所有生物标志物均异常。在开始血液透析后，响应于患者血清的人足细胞上的β3整联蛋白活性以及AT 1 R-Ab进一步升高。在活检证实复发时，所有生物标志物均异常高。在中止血浆置换（继发于不耐受）和高剂量类固醇治疗后1周，Palb和suPAR-β3整合素活性仍显著阳性。经过12周的高剂量类固醇，利妥昔单抗和半乳糖治疗，患者仍然依赖血液透析。在他初次就诊后三个月，我们开始使用促肾上腺皮质激素（ACTH，Acthar®凝胶），每周两次皮下注射80单位。四周后，他能够停止透析。在8个月的ACTH维持治疗后，他的血清肌酐稳定在1.79 mg/dL，蛋白尿<1 g。结论：ACTH治疗与4周内肾功能改善相关。使用rFSGS生物标志物可能有助于预测rFSGS的发展。
Background: Recurrent focal segmental glomerular sclerosis (rFSGS) in renal transplant recipients (RTR) is difficult to predict and treat. Early rFSGS is likely from circulating factors and preformed antibodies. Methods: We present the case of a 23-year-old white man who presented with rFSGS and acute renal failure, requiring dialysis 9-months after a 1-haplotype matched living-related transplant. We retrospectively analyzed serum samples from various clinical stages for rFSGS biomarkers: serum glomerular albumin permeability (Palb), soluble urokinase-type plasminogen activator receptor (suPAR) serum level with suPAR-β3 integrin signaling on human podocytes, and angiotensin II type I receptor-antibody (AT1R-Ab) titer. Results: All biomarkers were abnormal at 1-year pre-transplant prior to initiation of dialysis and at the time of transplant. After initiation of hemodialysis, β3 integrin activity on human podocytes, in response to patient serum, as well as AT1R-Ab were further elevated. At the time of biopsy-proven recurrence, all biomarkers were abnormally high. One week after therapy with aborted plasmapheresis (secondary to intolerance), and high dose steroids, the Palb and suPAR-β3 integrin activity remained significantly positive. After 12-weeks of treatment with high-dose steroids, rituximab, and galactose, the patient remained hemodialysis-dependent. Three-months after his initial presentation, we commenced adrenocorticotropic hormone (ACTH, Acthar® Gel), 80 units subcutaneously twice weekly. Four-weeks later, he was able to discontinue dialysis. After 8-months of maintenance ACTH therapy, his serum creatinine stabilized at 1.79 mg/dL with <1 g of proteinuria. Conclusion: ACTH therapy was associated with improvement in renal function within 4 weeks. The use of rFSGS biomarkers may aid in predicting development of rFSGS.