Medicine- Nephrology, University of Florida, Gainesville, FL, USA.
Medicine-Nephrology, Virginia Commonwealth University, Richmond, VA, USA.
Transpl Infect Dis. 2021 Apr;23(2):e13508. doi: 10.1111/tid.13508. Epub 2020 Nov 29.
Immunosuppression reduction for BK viremia is associated with de novo humoral responses, which are a risk factor for rejection and graft loss. In this pilot project, we tested a protocol of immunosuppression resumption to standard dose after viral clearance for optimal protection against humoral immunity in patients undergoing treatment for BK viremia.
Thirty-six consecutive kidney transplant recipients who developed BK viremia from 7/1/2014 to 11/18/2016 underwent immunosuppression reduction. After 4 weeks of absent viremia, mycophenolate mofetil (MMF) was increased by 500mg/day every 2 weeks up to standard dosage, followed by increase of tacrolimus trough levels to 5-7 ng/mL. If viremia recurred during the increase, immunosuppression was reduced in this same stepwise fashion, with stepwise increase again after 2 months of negative viremia.
Mean tacrolimus trough level (ng/mL) was 8.3 ± 2.7 at viremia onset, 5.3 ± 3.6 at resolution, and 5.6 ± 2.0 at study end date. Mean daily dose (mg) of MMF was 1574 ± 355 at onset, 910 ± 230 at resolution, and 1377 ± 451 at study end date. Only one patient developed low level viremia recurrence (peak 2875 copies/mL) during the period of immunosuppression resumption that ultimately resolved.
The results of our pilot project indicate that following BK viremia resolution, resumption of standard immunosuppression can be achieved safely without BK viremia recurrence. Larger trials with long-term follow up are required to determine whether such an approach improves long-term graft survival.
BK 病毒血症的免疫抑制减少与新的体液反应有关,这是排斥反应和移植物丢失的一个危险因素。在这个试点项目中,我们测试了一种在病毒清除后恢复到标准剂量的免疫抑制方案,以在接受 BK 病毒血症治疗的患者中针对体液免疫提供最佳保护。
2014 年 7 月 1 日至 2016 年 11 月 18 日,36 例连续接受肾移植的患者出现 BK 病毒血症,接受免疫抑制减少治疗。在 4 周无病毒血症后,每隔 2 周将霉酚酸酯(MMF)增加 500mg/天,增加到标准剂量,然后将他克莫司谷浓度增加到 5-7ng/mL。如果在增加过程中病毒血症再次出现,则以同样的逐步方式减少免疫抑制,在病毒血症持续阴性 2 个月后再次逐步增加。
病毒血症发病时的平均他克莫司谷浓度(ng/mL)为 8.3±2.7,病毒血症缓解时为 5.3±3.6,研究结束时为 5.6±2.0。MMF 的平均日剂量(mg)为 1574±355 时发病,910±230 时缓解,1377±451 时研究结束。只有 1 例患者在免疫抑制恢复期间出现低水平病毒血症复发(峰值 2875 拷贝/mL),最终得到缓解。
我们的试点项目结果表明,在 BK 病毒血症缓解后,恢复标准免疫抑制可以安全地进行,而不会导致 BK 病毒血症复发。需要进行更大规模的、具有长期随访的试验,以确定这种方法是否能提高长期移植物存活率。