Davis S, Gralla J, Chan L, Wiseman A, Edelstein C L
Division of Renal Diseases and Hypertension, University of Colorado, Aurora, Colorado.
Department of Pediatrics, University of Colorado, Aurora, Colorado.
Transplant Proc. 2018 Jun;50(5):1243-1248. doi: 10.1016/j.transproceed.2018.02.060.
The mammalian target of rapamycin (mTOR) pathway has been shown to be central to cyst formation and growth in patients with autosomal dominant polycystic kidney disease (ADPKD). Drugs that suppress mTOR signaling are frequently used as antiproliferative agents for maintenance immunosuppression in patients who have undergone kidney transplantation. The aim of this study was to determine the effect of sirolimus, an mTOR inhibitor, on cyst volume regression in patients with ADPKD who have undergone renal transplantation.
In this single-center, prospective, open-label, parallel-group, randomized trial, 23 adult patients with ADPKD who successfully underwent renal transplantation from 2008 to 2012 were subsequently randomized (on a 1:1 basis) to a maintenance immunosuppression regimen with either sirolimus (sirolimus, tacrolimus, prednisone) or mycophenolate (mycophenolate, tacrolimus, prednisone). Total kidney volumes were measured by means of high-resolution magnetic resonance imaging within 2 weeks after transplantation and at 1 year. The primary end point was change in total kidney volume at 1 year.
Sixteen patients completed the 1-year study (8 patients in each group). There was a decrease in kidney volume in both the sirolimus group (percentage change from baseline, 20.5%; P < .001) and mycophenolate group (percentage change from baseline, 17%; P = .048), but there was no significant difference in percentage change of total kidney volume between the groups (P = .665).
In ADPKD patients at 1 year after kidney transplantation, there was a similar decrease in polycystic kidney volume in patients receiving an immunosuppression regimen containing sirolimus compared with patients receiving mycophenolate.
哺乳动物雷帕霉素靶蛋白(mTOR)信号通路已被证明在常染色体显性遗传性多囊肾病(ADPKD)患者的囊肿形成和生长中起核心作用。抑制mTOR信号传导的药物经常被用作肾移植患者维持免疫抑制的抗增殖药物。本研究的目的是确定mTOR抑制剂西罗莫司对已接受肾移植的ADPKD患者囊肿体积消退的影响。
在这项单中心、前瞻性、开放标签、平行组、随机试验中,23例在2008年至2012年成功接受肾移植的成年ADPKD患者随后被(按1:1比例)随机分配至接受含西罗莫司(西罗莫司、他克莫司、泼尼松)或霉酚酸酯(霉酚酸酯、他克莫司、泼尼松)的维持免疫抑制方案。在移植后2周内及1年时通过高分辨率磁共振成像测量双肾总体积。主要终点是1年时双肾总体积的变化。
16例患者完成了1年的研究(每组8例)。西罗莫司组(相对于基线的百分比变化为20.5%;P <.001)和霉酚酸酯组(相对于基线的百分比变化为17%;P = 0.048)的肾体积均有减小,但两组间双肾总体积的百分比变化无显著差异(P = 0.665)。
在肾移植后1年的ADPKD患者中,与接受霉酚酸酯的患者相比,接受含西罗莫司免疫抑制方案的患者多囊肾体积有相似程度的减小。