Funk G A, Gosert R, Comoli P, Ginevri F, Hirsch H H
Transplantation Virology, Institute for Medical Microbiology, Department of Biomedicine, University of Basel, Basel, Switzerland.
Am J Transplant. 2008 Nov;8(11):2368-77. doi: 10.1111/j.1600-6143.2008.02402.x.
Fast BK virus (BKV) replication in renal tubular epithelial cells drives polyomavirus-BK-associated nephropathy (PVAN) to premature kidney transplant (KT) failure. BKV also replicates in urothelial cells, but remains asymptomatic in two-thirds of affected KT patients. Comparing 518 day-matched plasma-urine samples from 223 KT patients, BKV loads were approximately 3000-fold higher in urine than in plasma (p < 0.000001). Molecular and quantitative parameters indicated that >95% of urine BKV loads resulted from urothelial replication and <5% from tubular epithelial replication. Fast BKV replication dynamics in plasma and urine with half-lives of <12 h accounted for daily urothelial and tubular epithelial cell loss of 4 x 10(7) and 6 x 10(7), respectively. BKV dynamics in both sites were only partly linked, with full and partial discordance in 36% and 32%, respectively. Viral expansion was best explained by models where BKV replication started in the kidney followed by urothelial amplification and tubular epithelial cell cross-feeding reaching a dynamic equilibrium after approximately 10 weeks. Curtailing intrarenal replication by 50% was ineffective and >80% was required for clearing viremia within 7 weeks, but viruria persisted for >14 weeks. Reductions >90% cleared viremia and viruria by 3 and 10 weeks, respectively. The model was clinically validated in prospectively monitored KT patients supporting >80% curtailing for optimal interventions.
肾小管上皮细胞中BK病毒（BKV）的快速复制会导致多瘤病毒BK相关性肾病（PVAN），使肾移植（KT）过早失败。BKV也会在上皮细胞中复制，但在三分之二受影响的KT患者中仍无症状。比较223名KT患者的518份日匹配血浆-尿液样本，尿液中的BKV载量比血浆中高约3000倍（p < 0.000001）。分子和定量参数表明，>95%的尿液BKV载量来自上皮细胞复制，<5%来自肾小管上皮细胞复制。血浆和尿液中BKV的快速复制动态，半衰期<12小时，分别导致每日上皮细胞和肾小管上皮细胞损失4×10⁷和6×10⁷。两个部位的BKV动态仅部分相关，完全不一致和部分不一致的情况分别为36%和32%。病毒扩增最好用以下模型解释：BKV复制始于肾脏，随后是上皮细胞扩增和肾小管上皮细胞交叉喂养，约10周后达到动态平衡。将肾内复制减少50%无效，需要减少>80%才能在7周内清除病毒血症，但病毒尿持续>14周。减少>90%分别在3周和10周时清除病毒血症和病毒尿。该模型在前瞻性监测的KT患者中得到临床验证，支持减少>80%以进行最佳干预。
