Al-Talib Mohammed, Welberry-Smith Matthew, Macdonald Andrew, Griffin Siân
Systems Immunity Research Institute, Division of Infection and Immunity, School of Medicine, Cardiff University, Cardiff, UK.
Bristol Medical School, University of Bristol, 5 Tyndall Avenue, Bristol, UK.
Nephrol Dial Transplant. 2025 Apr 1;40(4):651-661. doi: 10.1093/ndt/gfaf002.
BK polyomavirus (BKPyV) is recognized as a significant viral complication of kidney transplantation. Prompt immunosuppression reduction reduces early graft failure rates due to BK polyomavirus-associated nephropathy (BKPyVAN), however, modulation of immunosuppression can lead to acute rejection. Medium-to-long-term graft outcomes are negatively affected by BKPyVAN, probably due to a combination of virus-induced graft damage and host immune responses against graft alloantigens potentiated by immunosuppression reduction. Kidney biopsy remains the gold-standard diagnostic test, however, false-negative findings are common due to the focal nature of BKPyVAN. BKPyV DNAemia, as measured by quantitative polymerase chain reaction, is established as a screening test but there is at present no (inter)national standardization of these assays to allow collation and comparison of data between centres. Randomized controlled trials are lacking both in terms of optimal immunosuppression reduction strategies, and for the medications variably used to attempt treatment in clinical practice. Much of the fundamental biology of BKPyV is not yet understood, and further elucidation is required to promote rational direct-acting antiviral drug design. Insights into the role of adaptive immunity in control of BKPyV have informed the design of novel treatments such as adoptive immunotherapies and neutralizing antibodies that require evaluation in clinical studies. Here, we review the current standards of diagnosis and treatment of BKPyVAN and discuss novel developments in the pathophysiology, diagnosis, outcome prediction, and management.
BK多瘤病毒(BKPyV)被认为是肾移植的一种重要病毒并发症。及时降低免疫抑制可降低因BK多瘤病毒相关性肾病(BKPyVAN)导致的早期移植肾失功率,然而,调整免疫抑制可能会导致急性排斥反应。BKPyVAN对移植肾的中长期预后有负面影响,这可能是由于病毒诱导的移植肾损伤以及免疫抑制降低所增强的宿主针对移植肾同种异体抗原的免疫反应共同作用的结果。肾活检仍然是金标准诊断测试,然而,由于BKPyVAN的局灶性,假阴性结果很常见。通过定量聚合酶链反应测量的BKPyV病毒血症已被确立为一种筛查测试,但目前这些检测方法尚无(国际)标准化,无法进行各中心之间的数据整理和比较。在最佳免疫抑制降低策略以及临床实践中用于尝试治疗的各种药物方面,均缺乏随机对照试验。BKPyV的许多基础生物学特性尚未被了解,需要进一步阐明以促进合理的直接作用抗病毒药物设计。对适应性免疫在控制BKPyV中的作用的深入了解为新型治疗方法的设计提供了思路,如过继性免疫疗法和中和抗体,这些都需要在临床研究中进行评估。在此,我们综述了BKPyVAN的当前诊断和治疗标准,并讨论了病理生理学、诊断、预后预测和管理方面的新进展。