Gregorini Marilena, Del Fante Claudia, Islami Tefik, Grignano Maria Antonietta, Serpieri Nicoletta, Perotti Cesare, Viarengo Gianluca, Locurcio Alessia, Lanotte Giuseppe, Tragni Alessandro, Stea Emma Diletta, Martinelli Chiara, Marchi Alessandro, Portalupi Valentina, De Mauri Andreana, Margiotta Elisabetta, Pattonieri Eleonora Francesca, Soccio Grazia, Rampino Teresa
Unit of Nephrology, Dialysis and Transplantation, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Policlinico San Matteo, Pavia, Italy.
Department of Internal Medicine and Therapeutics, University of Pavia, Pavia, Italy.
Front Nephrol. 2025 Jul 21;5:1625060. doi: 10.3389/fneph.2025.1625060. eCollection 2025.
BK virus-associated nephropathy (BKVAN) is a major complication in kidney transplantation caused by the reactivation of latent BK virus (BKV) under immunosuppression. BKVAN has been strongly associated with increased graft loss. Currently, there is no effective antiviral treatment for BKVAN. Additionally, the development of donor-specific antibodies (DSAs) and the risk of acute and chronic rejection complicate the reduction of immunosuppressive therapy (IS). This case report illustrates the management of BKVAN in a highly sensitized transplant recipient and explores the potential use of extracorporeal photopheresis (ECP) as an immunomodulatory tool.
44-year-old Caucasian woman with a history of failed prior transplant and multiple transfusions underwent a second kidney transplant. Due to a high panel-reactive antibody level, she received induction therapy with plasma exchange, thymoglobulin and steroids, followed by maintenance with tacrolimus, mycophenolate mofetil (MMF), and steroids. Initial graft function was good, and protocol biopsies showed no rejection. In year four, the patient developed an increasing BKV viremia (peak of 40,050 copies/mL) and MMF was reduced, which cleared BKV in six months. Two years later, DSAs reappeared, which led to an increase in MMF. In August 2020 the patient showed a decline of GFR, elevated BKV viremia (peak 162,000 copies/mL), and a graft biopsy was performed revealing BKVAN. IS was reduced (MMF was discontinued, and tacrolimus was tapered). After eight months, the viremia cleared up, but anti-DR53 DSAs (MFI 16000) levels increased significantly. As the patient was highly sensitized and had a thrombosis of arteriovenous fistula, mTOR inhibitors were not recommended. In order to modulate alloimmunity without further suppressing antiviral immunity, ECP was introduced. Over the next two years, the patient showed stable renal function (eGFR 30-40 mL/min), no recurrence of BKV viremia, and a gradual reduction in DSAs titers. No acute rejection episodes occurred.
In a highly sensitized patient with BKVAN and contraindications to standard therapies, ECP combined with a tailored immunosuppressive regimen proved effective in controlling viral replication, preserving graft function, and mitigating alloimmune risks. Considering the potential of ECP as an adjunctive therapy in complex BKVAN scenarios, further investigation is warranted.
BK病毒相关性肾病(BKVAN)是肾移植中的一种主要并发症,由潜伏的BK病毒(BKV)在免疫抑制状态下重新激活所致。BKVAN与移植肾丢失增加密切相关。目前,尚无针对BKVAN的有效抗病毒治疗方法。此外,供者特异性抗体(DSA)的产生以及急性和慢性排斥反应的风险使免疫抑制治疗(IS)的减少变得复杂。本病例报告阐述了对一名高敏移植受者BKVAN的管理,并探讨了体外光化学疗法(ECP)作为一种免疫调节工具的潜在用途。
一名44岁的白种女性,既往有移植失败史且多次输血,接受了第二次肾移植。由于群体反应性抗体水平较高,她接受了血浆置换、抗胸腺细胞球蛋白和类固醇的诱导治疗,随后用他克莫司、霉酚酸酯(MMF)和类固醇维持治疗。移植肾初始功能良好,方案活检未显示排斥反应。在第4年,患者出现BKV病毒血症增加(峰值为40,050拷贝/mL),MMF剂量减少,6个月后BKV清除。两年后,DSA再次出现,导致MMF增加。2020年8月,患者肾小球滤过率(GFR)下降,BKV病毒血症升高(峰值162,000拷贝/mL),进行了移植肾活检,结果显示为BKVAN。IS减少(停用MMF,逐渐减少他克莫司剂量)。8个月后,病毒血症清除,但抗DR53 DSA(平均荧光强度16000)水平显著升高。由于患者高度敏感且存在动静脉内瘘血栓形成,不推荐使用mTOR抑制剂。为了在不进一步抑制抗病毒免疫的情况下调节同种免疫,引入了ECP。在接下来的两年里,患者肾功能稳定(估算肾小球滤过率30 - 40 mL/min),BKV病毒血症未复发,DSA滴度逐渐降低。未发生急性排斥反应。
在一名对标准治疗有禁忌证的高敏BKVAN患者中,ECP联合定制的免疫抑制方案被证明在控制病毒复制、维持移植肾功能和降低同种免疫风险方面有效。鉴于ECP在复杂BKVAN病例中作为辅助治疗的潜力,有必要进行进一步研究。