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肾移植急性排斥反应与霉酚酸酯低剂量和质子泵抑制剂或组胺 2 受体拮抗剂。

Renal Transplant Acute Rejection with Lower Mycophenolate Mofetil Dosing and Proton Pump Inhibitors or Histamine-2 Receptor Antagonists.

机构信息

Department of Pharmacy, Cleveland Clinic, Cleveland, Ohio.

Department of Nephrology and Hypertension, Cleveland Clinic, Cleveland, Ohio.

出版信息

Pharmacotherapy. 2017 Dec;37(12):1507-1515. doi: 10.1002/phar.2037. Epub 2017 Nov 28.

Abstract

BACKGROUND

Pharmacokinetic data show reduced mycophenolic acid levels in renal transplant recipients taking mycophenolate mofetil (MMF) and proton pump inhibitors (PPIs) concomitantly. This reduced exposure could increase rejection risk. The typical initial MMF dose post renal transplantation is 2 g/day, which often requires dose reduction secondary to side effects. Existing studies have not shown significant acute rejection differences for patients taking MMF-PPI versus patients taking MMF-ranitidine.

OBJECTIVE

The purpose of this study was to evaluate clinical outcomes in renal transplant recipients receiving a lower MMF dose than previously studied (1.5 g/day) and either a PPI or histamine-2 receptor antagonist (H2RA).

METHODS

This retrospective cohort study included adult subjects receiving a renal transplant between January 1, 2009, and June 30, 2013. Comparison groups were defined based on acid-suppressing therapy class prescribed at discharge from transplantation. The primary outcome was acute rejection incidence within 1 year posttransplantation.

RESULTS

Of 728 renal transplant recipients screened, 522 were included: 183 taking a PPI and 339 taking an H2RA. There was no significant difference in acute rejection within 1 year (H2RA 19% versus PPI 14%, p=0.12) or 3 months (4% vs 5%, p=0.44, respectively) posttransplantation. Maintenance immunosuppression (MMF dose and tacrolimus troughs) was similar between groups at 3 months and 1 year. Graft and patient survivals were favorable (> 95%), and graft function at 1 year was stable and similar between groups.

CONCLUSION

Despite taking lower MMF doses than previously studied, subjects on a PPI compared to an H2RA were not at increased risk of acute rejection within 1 year posttransplantation.

摘要

背景

药代动力学数据显示,同时服用吗替麦考酚酯(MMF)和质子泵抑制剂(PPIs)的肾移植受者体内的麦考酚酸水平降低。这种暴露量的减少可能会增加排斥反应的风险。肾移植后 MMF 的典型初始剂量为 2g/天,由于副作用,通常需要降低剂量。现有研究表明,服用 MMF-PPI 的患者与服用 MMF-雷尼替丁的患者相比,急性排斥反应无显著差异。

目的

本研究旨在评估接受低于先前研究(1.5g/天)剂量 MMF 治疗的肾移植受者的临床结果,这些患者同时接受质子泵抑制剂或组胺 2 受体拮抗剂(H2RA)治疗。

方法

本回顾性队列研究纳入了 2009 年 1 月 1 日至 2013 年 6 月 30 日期间接受肾移植的成年患者。根据出院时开具的抑酸治疗药物类别将比较组定义。主要结局是移植后 1 年内的急性排斥反应发生率。

结果

在筛选的 728 名肾移植受者中,522 名符合入选标准:183 名患者服用 PPI,339 名患者服用 H2RA。移植后 1 年内(H2RA 为 19%,PPI 为 14%,p=0.12)或 3 个月(4%比 5%,p=0.44)内急性排斥反应发生率无显著差异。移植后 3 个月和 1 年时,两组的维持性免疫抑制(MMF 剂量和他克莫司谷浓度)相似。移植物和患者存活率均较好(>95%),1 年后移植物功能稳定且两组间无差异。

结论

尽管服用的 MMF 剂量低于先前的研究,但与 H2RA 相比,服用 PPI 的患者在移植后 1 年内发生急性排斥反应的风险并未增加。

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