Caillard Sophie, Meyer Nicolas, Solis Morgane, Bertrand Dominique, Jaureguy Maite, Anglicheau Dany, Ecotiere Laure, Buchler Matthias, Bouvier Nicolas, Schvartz Betoul, Rerolle Jean Philippe, Heng Anne Elisabeth, Couzi Lionel, Duveau Agnes, Morelon Emmanuel, LeMeur Yann, Golbin Léonard, Thervet Eric, Benotmane Ilies, Fafi-Kremer Samira
Department of Nephrology, Dialysis and Transplantation, Institut National de la Santé et de la Recherche Médicale (INSERM), Immuno-Rhumatologie Moléculaire (IRM) Unité Mixte de Recherche (UMR)-S 1109, Strasbourg University Hospital, Strasbourg, France.
Department of Public Health, Strasbourg University Hospital, Strasbourg, France.
Kidney Int. 2025 Feb;107(2):338-347. doi: 10.1016/j.kint.2024.09.018. Epub 2024 Oct 28.
The MTOR inhibitors have demonstrated antiviral properties, and prior non-randomized studies have suggested they may have a suppressive effect on BKPyV replication. Here, in this randomized, multicenter, controlled trial (BKEVER study), we sought to evaluate the impact of everolimus (EVR) in facilitating the clearance of BKPyV compared to simply reducing immunosuppression among kidney transplant recipients (KTRs). All together, 130 KTRs presenting with BKPyV DNAemia were randomized 1:1 into two groups. The EVR group, in which mycophenolate mofetil (MMF) was replaced by EVR along with a decrease in calcineurin inhibitor trough levels and secondly the MMF group, in which the MMF dose was decreased by half along with a similar lowering of calcineurin inhibitor levels. The primary endpoint was the proportion of patients achieving viral clearance at six months. Secondary endpoints included the kinetics of BKPyV replication over time, the incidence of BKPyV-associated nephropathy, kidney graft function, the incidence of kidney graft rejection, and medication tolerability over two years. Significantly, BKPyV clearance was achieved in 55.7% of patients in the EVR group compared to 81.3% of patients in the MMF group at six months. The reduction in BKPyV DNA load was significantly more rapid in the MMF group. Calcineurin inhibitor trough levels were within expected target ranges and did not differ meaningfully between the two groups from randomization through month six. Two grafts were lost, and four patients died. Eleven patients in the EVR group and six patients in the MMF group developed biopsy-proven BKPyV nephropathy. Thus, in KTRs with BKPyV DNAemia, replacing MMF with EVR along with lowering calcineurin inhibitor levels did not lead to more frequent or faster clearance of BKPyV.
mTOR抑制剂已显示出抗病毒特性，先前的非随机研究表明它们可能对BK多瘤病毒（BKPyV）复制有抑制作用。在此，在这项随机、多中心、对照试验（BKEVER研究）中，我们试图评估与单纯减少肾移植受者（KTR）的免疫抑制相比，依维莫司（EVR）在促进BKPyV清除方面的影响。总共130例出现BKPyV病毒血症的KTR被1:1随机分为两组。EVR组，用EVR替代霉酚酸酯（MMF），同时降低钙调神经磷酸酶抑制剂的谷浓度；第二组为MMF组，将MMF剂量减半，同时类似地降低钙调神经磷酸酶抑制剂水平。主要终点是六个月时实现病毒清除的患者比例。次要终点包括BKPyV复制随时间的动力学、BKPyV相关性肾病的发生率、肾移植功能、肾移植排斥反应的发生率以及两年内的药物耐受性。值得注意的是，六个月时EVR组55.7%的患者实现了BKPyV清除，而MMF组为81.3%。MMF组中BKPyV DNA载量的降低明显更快。钙调神经磷酸酶抑制剂的谷浓度在预期目标范围内，从随机分组到第六个月，两组之间没有显著差异。有两个移植肾丢失，四名患者死亡。EVR组有11例患者和MMF组有6例患者发生了经活检证实的BKPyV肾病。因此，在患有BKPyV病毒血症的KTR中，用EVR替代MMF并降低钙调神经磷酸酶抑制剂水平并不能导致BKPyV更频繁或更快地清除。
