Ginevri F, Azzi A, Hirsch H H, Basso S, Fontana I, Cioni M, Bodaghi S, Salotti V, Rinieri A, Botti G, Perfumo F, Locatelli F, Comoli P
Pediatric Nephrology Unit, G. Gaslini Institute, Genova, Italy.
Am J Transplant. 2007 Dec;7(12):2727-35. doi: 10.1111/j.1600-6143.2007.01984.x. Epub 2007 Oct 1.
Polyoma BK virus (BKV)-associated nephropathy (PVAN) is a relevant cause of poor renal allograft survival. In a prospective analysis, we monitored BKV DNA in blood and urine samples from 62 consecutive pediatric kidney recipients. In patients with BKV replication, we analyzed the impact of reduction of maintenance immunosuppression on viral load kinetics and PVAN in patients with BKV replication. BKV-specific immunity was concomitantly evaluated on blood samples of viremic patients, by measuring the frequency of BKV-specific interferon-gamma-producing and cytotoxic T cells, and BKV IgG antibody levels. At a median follow-up of 24 months, BK viruria was observed in 39 of 62 patients, while BK viremia developed in 13 patients (21%). In all viremic patients, immunosuppression reduction resulted in the clearance of viremia, and prevented development of PVAN, without increasing the rate of acute rejection or causing graft dysfunction. As a consequence of immunosuppression adjustment, an expansion of BKV-specific cellular immunity was observed that coincided with viral clearance. We conclude that treating pediatric kidney transplant patients pre-emptively with immunosuppression reduction guided by BKV DNA in blood is safe and effective to prevent onset of PVAN. BKV-specific cellular immunity may be useful to guide this intervention.
多瘤BK病毒(BKV)相关性肾病(PVAN)是导致肾移植存活率低下的一个相关原因。在一项前瞻性分析中,我们监测了62例连续儿科肾移植受者血液和尿液样本中的BKV DNA。对于BKV复制的患者,我们分析了维持性免疫抑制降低对BKV复制患者病毒载量动力学和PVAN的影响。通过测量BKV特异性干扰素-γ产生细胞和细胞毒性T细胞的频率以及BKV IgG抗体水平,同时对病毒血症患者的血液样本进行BKV特异性免疫评估。在中位随访24个月时,62例患者中有39例出现BK病毒尿,13例患者(21%)发生BK病毒血症。在所有病毒血症患者中,免疫抑制降低导致病毒血症清除,并预防了PVAN的发生,而没有增加急性排斥反应的发生率或导致移植物功能障碍。作为免疫抑制调整的结果,观察到BKV特异性细胞免疫的扩展,这与病毒清除同时发生。我们得出结论,以血液中的BKV DNA为指导,对儿科肾移植患者进行免疫抑制降低的预防性治疗,对于预防PVAN的发生是安全有效的。BKV特异性细胞免疫可能有助于指导这种干预。