Department of Pharmacy Services, Michigan Medicine, Ann Arbor, MI, USA.
Nephrology Associates of Michigan, Ypsilanti, MI, USA.
Transpl Infect Dis. 2021 Apr;23(2):e13472. doi: 10.1111/tid.13472. Epub 2020 Oct 7.
Reducing immunosuppression can effectively treat BK viremia (BKV) and BK nephropathy, but has been associated with increased risks for acute rejection and development of donor-specific antibodies (DSA). To date there have been no systematic evaluations of re-escalating immunosuppression in transplant patients with resolving BKV. Importantly, the safety of this approach and impact on graft survival is unclear.
We performed a single-center retrospective review of kidney transplant recipients between July 2011 and June 2013 who had immunosuppression reduction after developing BKV (plasma PCR ≥ 1000 copies/ml). Changes in immunosuppression and patient outcomes were tracked until occurrence of a complication event: biopsy-proven acute rejection (BPAR), detection of de novo DSA, or recurrent BKV. Patients were grouped according to whether or not net immunosuppression was eventually increased.
Out of 88 patients with BKV, 44 (50%) had net immunosuppression increased while the other 44 did not. Duration of viremia, peak viremia, induction, and sensitization status were similar between the two groups. In a Kaplan-Meier analysis, increasing immunosuppression was associated with less BPAR (P = .001) and a trend toward less de novo DSA development (P = .06). Death-censored graft survival (P = .27) was not different between the two groups. In the net immunosuppression increase group, recurrent BKV occurred in 22.7% without any BKV-related graft losses.
These findings support potential benefits of increasing immunosuppression in patients with low-level or resolved BKV, but prospective trials are needed to better understand such an approach.
降低免疫抑制可以有效治疗 BK 病毒血症(BKV)和 BK 肾病,但与急性排斥反应和供体特异性抗体(DSA)的发展风险增加相关。迄今为止,对于 BKV 已解决的移植患者,尚无关于重新增加免疫抑制的系统评估。重要的是,这种方法的安全性及其对移植物存活率的影响尚不清楚。
我们对 2011 年 7 月至 2013 年 6 月期间因 BKV 而降低免疫抑制的肾移植受者进行了单中心回顾性研究(血浆 PCR≥1000 拷贝/ml)。在发生并发症事件(活检证实的急性排斥反应(BPAR)、新出现的 DSA 检测或复发性 BKV)之前,跟踪免疫抑制的变化和患者的结局。根据最终是否增加净免疫抑制将患者分为两组。
在 88 例 BKV 患者中,44 例(50%)最终增加了净免疫抑制,而另外 44 例没有。两组之间的病毒血症持续时间、病毒血症峰值、诱导和致敏状态相似。在 Kaplan-Meier 分析中,增加免疫抑制与较少的 BPAR(P=0.001)和较少的新出现 DSA 发展趋势(P=0.06)相关。两组之间的死亡相关移植物存活率(P=0.27)没有差异。在净免疫抑制增加组中,22.7%的患者出现复发性 BKV,而没有任何与 BKV 相关的移植物丢失。
这些发现支持在低水平或已解决的 BKV 患者中增加免疫抑制的潜在益处,但需要前瞻性试验来更好地了解这种方法。