研究方案：一项初步研究，旨在确定诱导治疗、新型 MPA 和延迟 mTOR 抑制在肾功能受损的肝移植受者中的安全性和疗效。PATRON 研究。

Study protocol: a pilot study to determine the safety and efficacy of induction-therapy, de novo MPA and delayed mTOR-inhibition in liver transplant recipients with impaired renal function. PATRON-study.

机构信息

Department of Surgery, Regensburg University Hospital, Regensburg, Germany.

出版信息

BMC Nephrol. 2010 Sep 14;11:24. doi: 10.1186/1471-2369-11-24.

DOI:10.1186/1471-2369-11-24

PMID:20840760

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2945344/

Abstract

BACKGROUND

Patients undergoing liver transplantation with preexisting renal dysfunction are prone to further renal impairment with the early postoperative use of Calcineurin-inhibitors. However, there is only little scientific evidence for the safety and efficacy of de novo CNI free "bottom-up" regimens in patients with impaired renal function undergoing liver transplantation. This is a single-center study pilot-study (PATRON07) investigating safety and efficacy of CNI-free, "bottom-up" immunosuppressive (IS) strategy in patients undergoing liver transplantation (LT) with renal impairment prior to LT.

METHODS/DESIGN: Patients older than 18 years with renal impairment at the time of liver transplantation eGFR < 50 ml/min and/or serum creatinine levels > 1.5 mg/dL will be included. Patients in will receive a CNI-free combination therapy (basiliximab, MMF, steroids and delayed Sirolimus). Primary endpoint is the incidence of steroid resistant acute rejection within the first 30 days after LT. The study is designed as prospective two-step trial requiring a maximum of 29 patients. In the first step, 9 patients will be included. If 8 or more patients show no signs of biopsy proven steroid resistant rejection, additional 20 patients will be included. If in the second step a total of 27 or more patients reach the primary endpoint the regimen is regarded to be safe and efficient.

DISCUSSION

If a CNI-free-"bottom-up" IS strategy is safe and effective, this may be an innovative concept in contrast to classic top-down strategies that could improve the patient short and long-time renal function as well as overall complications and survival after LT. The results of PATRON07 may be the basis for a large multicenter RCT investigating the new "bottom-up" immunosuppressive strategy in patients with poor renal function prior to LT.http://www.clinicaltrials.gov-identifier: NCT00604357.

摘要

背景

患有预先存在肾功能障碍的患者在接受肝移植后早期使用钙调神经磷酸酶抑制剂（Calcineurin-inhibitors）会进一步导致肾功能损害。然而，对于肾功能受损的患者在接受肝移植（LT）之前，使用新型无钙调神经磷酸酶抑制剂（CNI）“自上而下”方案的安全性和有效性，仅有少量科学证据。这是一项单中心研究（PATRON07），旨在调查预先存在肾功能障碍的患者在接受肝移植时使用无 CNI、“自下而上”的免疫抑制（IS）策略的安全性和有效性。

方法/设计：将纳入年龄大于 18 岁、肝移植时肾功能受损（eGFR<50ml/min 和/或血清肌酐水平>1.5mg/dL）的患者。患者将接受无 CNI 联合治疗（巴利昔单抗、MMF、类固醇和延迟西罗莫司）。主要终点是肝移植后 30 天内类固醇抵抗性急性排斥反应的发生率。该研究设计为需要最多 29 例患者的前瞻性两步试验。在第一步中，将纳入 9 例患者。如果 8 例或更多患者没有活检证实的类固醇抵抗性排斥反应的迹象，则纳入额外的 20 例患者。如果在第二步中共有 27 例或更多患者达到主要终点，则该方案被认为是安全有效的。

讨论

如果无 CNI-“自下而上”IS 策略是安全有效的，这可能是一种创新的概念，可以改善患者的短期和长期肾功能以及整体并发症和 LT 后的生存。PATRON07 的结果可能是一项新的大型多中心 RCT 的基础，该 RCT 旨在研究 LT 前肾功能不佳的患者的新型“自下而上”免疫抑制策略。http://www.clinicaltrials.gov 标识符：NCT00604357。