Supplementary Material for: Retrospective analysis of graft loss risk in patients with BK Polyomavirus associated nephropathy in relation to rejection status in a multicenter cohort with regular surveillance of BK Polyomavirus and donor specific antibody

Introduction: BK polyomavirus (BKPyV) in kidney transplant associated with adverse graft outcome. The aim of this study was to examine graft loss risk of BK polyomavirus associated nephropathy (BKPyVAN) and BKPyV-DNAemia in relation with de novo donor specific antibody and rejection status.
Methods: Two hundred and forty patients from a multicenter cohort who had regular BKPyV and donor specific antibody (DSA) surveillance were retrospectively reviewed and stratified according to the presence of BKPyV-DNAemia and rejection.
Results: BKPyV-DNAemia did not associate with de novo DSA development (Hazard Ratio [HR] 1.15, 95% confidence interval [CI] 0.50-2.67, p=0.74) but de novo DSA was more commonly observed in patients who developed rejection (BKV+/Rejection- 4.3% (n=2) vs BKV+/Rejection+ 57.1% (n=4), p<0.001). BKPyV-DNAemia (adjusted HR 4.02, 95%CI 1.30-12.43, p=0.016) and de novo DSA (adjusted HR 6.76, 95%CI 2.51-18.24, p<0.001) were independent factors associated with antibody mediated rejection. Patients with BKPyV-DNAemia who were further complicated with rejection had approximately 6-fold risk of graft loss (adjusted HR 6.24, 95% CI 2.04-19.09, p=0.001), whereas patient with BKPyV-DNAemia alone did not experience significant increase graft loss risk (adjusted HR 1.76, 95% CI 0.64-4.81, p=0.27).
Conclusions: Our study suggested that DSA monitoring would be warranted during immunosuppressant reduction for BKPyV-DNAemia and less aggressive reduction of when DSA emerges might be a reasonable strategy to avoid overzealous reduction of immunosuppressant that could precipitate allograft rejection.

引言：肾移植患者合并BK多瘤病毒（BK polyomavirus, BKPyV）感染与移植肾不良预后显著相关。本研究旨在探讨BK多瘤病毒相关性肾病（BK polyomavirus associated nephropathy, BKPyVAN）与BK多瘤病毒血症（BKPyV-DNAemia）的移植肾失功风险，及其与新生供者特异性抗体（de novo donor specific antibody, DSA）和排斥反应状态的关联。
方法：本研究回顾性分析了来自多中心队列的240例患者，所有患者均接受规律的BKPyV与供者特异性抗体（DSA）监测，并根据BKPyV-DNAemia的存在与否及排斥反应情况进行分层分组。
结果：BK多瘤病毒血症与新生DSA的发生无显著关联（风险比[HR] 1.15，95%置信区间[CI] 0.50～2.67，P＝0.74）；但发生排斥反应的患者中新生DSA的检出率显著更高：BKPyV阳性、排斥反应阴性组为4.3%（n=2），而BKPyV阳性、排斥反应阳性组达57.1%（n=4），P＜0.001。BK多瘤病毒血症（校正后HR 4.02，95%CI 1.30～12.43，P＝0.016）与新生DSA（校正后HR 6.76，95%CI 2.51～18.24，P＜0.001）均为抗体介导的排斥反应的独立危险因素。合并排斥反应的BK多瘤病毒血症患者，其移植肾失功风险约为对照组的6倍（校正后HR 6.24，95%CI 2.04～19.09，P＝0.001）；而仅存在BK多瘤病毒血症的患者，移植肾失功风险未出现显著升高（校正后HR 1.76，95%CI 0.64～4.81，P＝0.27）。
结论：本研究表明，在针对BK多瘤病毒血症实施免疫抑制剂减量治疗期间，应常规开展DSA监测；当检出新生DSA时，采用更为温和的免疫抑制剂减量策略，可避免过度减量诱发移植肾排斥反应，该策略具备临床合理性。