Emory University School of Medicine, Atlanta, Georgia, USA.
Children's Healthcare of Atlanta, Atlanta, Georgia, USA.
Pediatr Transplant. 2024 Aug;28(5):e14791. doi: 10.1111/petr.14791.
BK polyomavirus (BKV) DNAemia is a challenging infectious complication after kidney transplant (KT). Reduction of immunosuppression is the mainstay of management, and tacrolimus is often the first immunosuppressive medication adjusted upon the diagnosis of BKV DNAemia. This study aimed to evaluate the impact of a new institutional protocol with lower target tacrolimus levels on BKV DNAemia, allograft rejection, and de novo donor-specific antibodies (dnDSA) among pediatric KT recipients.
We conducted a retrospective chart review of all KT episodes between January 2013 and December 2018. The new protocol with lower target tacrolimus levels was implemented in March 2015. One hundred twenty-seven patients were included in primary analysis. All patients received induction with basiliximab and methylprednisolone and were maintained on a steroid-based immunosuppressive regimen.
In the post-intervention cohort, cumulative incidence of BKV DNAemia at 100 days (13.4% vs. 17.8%, p = .605) and 18 months post-KT (34.1% vs. 26.7%, p = .504) was not significantly different from the pre-intervention cohort. Biopsy-proven rejection rate did not change. However, we observed a trend toward earlier development of dnDSA in the post-intervention cohort using the Kaplan-Meier survival analysis (log-rank p = .06). Younger recipient age at the time of transplant was found to slightly increase the risk of BKV DNAemia (OR: 1.09, 95% CI [1.01, 1.16], p = .024). There was an association between BKV DNAemia and biopsy-proven rejection of any type (OR: 2.77, 95% CI [1.26, 6.23], p = .012), especially acute T-cell-mediated rejection grade 1A and above (OR: 2.95, 95% CI [1.06, 8.30], p = .037), after adjusted for recipient age at the time of transplant.
Targeting lower tacrolimus levels did not decrease the incidence of BKV DNAemia within 100 days or 18 months post-KT, nor did it increase the risk of biopsy-proven rejection among pediatric KT recipients in our center. However, there was a trend toward earlier development of dnDSA, which may portend worse long-term graft outcome post-KT. Our findings highlight the need for individualized immunosuppressive regimens based on immunologic and infectious risk factors and the importance of implementing innovative biomarkers to guide therapy and improve outcomes.
BK 多瘤病毒（BKV）血症是肾移植（KT）后具有挑战性的传染性并发症。减少免疫抑制是治疗的主要方法，而他克莫司通常是在诊断 BKV 血症后调整的第一种免疫抑制剂。本研究旨在评估新的机构方案，即较低的目标他克莫司水平对儿科 KT 受者的 BKV 血症、同种异体移植排斥和新供体特异性抗体（dnDSA）的影响。
我们对 2013 年 1 月至 2018 年 12 月期间所有 KT 发作进行了回顾性图表审查。新的方案，即较低的目标他克莫司水平，于 2015 年 3 月实施。127 例患者被纳入主要分析。所有患者均接受巴利昔单抗和甲基强的松龙诱导，并维持类固醇为基础的免疫抑制方案。
在干预后队列中，100 天（13.4%比 17.8%，p=0.605）和 18 个月（34.1%比 26.7%，p=0.504）的 BKV 血症累积发生率与干预前队列无显著差异。活检证实的排斥率没有改变。然而，我们通过 Kaplan-Meier 生存分析观察到干预后队列中 dnDSA 的发展趋势较早（对数秩 p=0.06）。移植时受者年龄较小，BKV 血症的风险略有增加（OR：1.09，95%CI[1.01，1.16]，p=0.024）。BKV 血症与任何类型的活检证实排斥之间存在关联（OR：2.77，95%CI[1.26，6.23]，p=0.012），尤其是急性 T 细胞介导的排斥 1A 级及以上（OR：2.95，95%CI[1.06，8.30]，p=0.037），在调整移植时受者年龄后。
在我们中心，目标是降低他克莫司水平，并未降低 KT 后 100 天或 18 个月内 BKV 血症的发生率，也未增加儿科 KT 受者活检证实排斥的风险。然而，dnDSA 的发展趋势较早，这可能预示着 KT 后移植的长期结果较差。我们的研究结果强调了根据免疫和感染危险因素制定个体化免疫抑制方案的必要性，以及实施创新生物标志物来指导治疗和改善结果的重要性。
