Tacrolimus and Plasmapheresis in Treatment-Resistant FSGS

描述（由申请人提供）：局灶节段性肾小球硬化（FSGS）在特发性肾病综合征的10-20%的儿童和5%的成人中观察到，在终末期肾病（ESRD）的儿童和5%的成人中观察到。相当数量的FSGS患者对皮质类固醇治疗没有反应，其他治疗方案的结果也令人失望。由于缺乏良好对照的前瞻性研究和大多数报告中纳入的患者数量较少，目前尚无针对类固醇耐药患者的循证治疗指南。2003年，NIDDK启动了一项多中心、前瞻性随机临床试验（FSGS- ct），比较环孢素a与霉酚酸酯和口服脉冲类固醇治疗方案在诱导类固醇耐药FSGS患者临床缓解方面的有效性。这项研究的招募将包括500名患者，从2004年开始，将持续到2008年1月底。对于两种FSGS-CT治疗方案均无效的患者，治疗选择非常有限。拟议的FSGS-CT辅助研究的目的是比较他克莫司与他克莫司加血浆置换在诱导对两种FSGS-CT治疗方案均无反应的患者的临床缓解方面的有效性。这项前瞻性先导研究将包括50名患者，他们将被随机分为两组，每组25名患者。两组患者（第一组和第二组）将接受他克莫司以及血管紧张素转换酶抑制剂或血管紧张素受体阻滞剂，为期6个月。第二组患者也将在最初的6周内接受15次血浆置换治疗。主要终点是26周研究结束时缓解的患者数量。本研究提案是代表中西部儿科肾脏病学会提交的，已获得FSGS-CT辅助研究委员会的批准，目前正在等待FSGS-CT指导委员会的最终批准。FSGS的诊断与一种无助感有关，因为它对目前使用的药物反应不佳，在相当数量的患者中进展为慢性肾功能衰竭，并且在移植肾脏中复发的风险很高。这项研究将为这些患者提供新的治疗选择，并使许多患者免于接受透析和肾移植的痛苦和困扰。

DESCRIPTION (provided by applicant): Focal segmental glomerulosclerosis (FSGS) is observed in 10-20% of children and 5% of adults with idiopathic nephrotic syndrome, and in 15% of children and 5% of adults with end-stage renal disease (ESRD). A significant number of patients with FSGS do not respond to corticosteroid therapy and the results of other therapeutic regimens have been disappointing. No evidence-based treatment guidelines exist for steroid- resistant patients because of the lack of well-controlled prospective studies and the small number of patients included in most reports. In 2003, NIDDK initiated a multicenter, prospective randomized, clinical trial (FSGS-CT) that will compare the effectiveness of cyclosporin A to a regimen of mycophenolate mofetil and oral pulse steroids in inducing clinical remission in patients with steroid-resistant FSGS. The recruitment for the study, which will include 500 patients, started in 2004 and will continue through the end of January 2008. Very limited therapeutic options exist in patients who fail to respond to either of the two treatment regimes of FSGS-CT. The aim of the proposed FSGS-CT ancillary study is to compare the effectiveness of tacrolimus with tacrolimus plus plasmapheresis in inducing clinical remission in patients who fail to respond to either of the two treatment regimens of FSGS-CT. This prospective pilot study will include 50 patients, who will be randomized into two groups of 25 patients each. Patients in both groups (Group 1 and II) will receive tacrolimus as well as angiotensin converting enzyme inhibitor or an angiotensin receptor blocker for a period of 6 months. Those in Group 2 will also receive 15 sessions of plasmapheresis over initial 6-week period. The primary endpoint is the number of patients in remission at the end of the study at 26 weeks. This study proposal, which is being submitted on behalf of the Midwest Pediatric Nephrology Consortium, has been approved by the Ancillary Studies Committee of the FSGS-CT, and is awaiting final approval by the FSGS-CT Steering Committee. The diagnosis of FSGS is associated with a sense of helplessness because of its poor response to the currently used medications, progression to chronic renal failure in a significant number of patients, and a high risk of recurrence in transplanted kidneys. The proposed study will offer new treatment options in such patients and save many from the pain and the distress of undergoing dialysis and renal transplantation.