Mühlbacher Thomas, Beck Robert, Nadalin Silvio, Heyne Nils, Guthoff Martina
Section of Nephrology and Hypertension, Dept. of Diabetology, Endocrinology, Nephrology, University of Tübingen, Tübingen, Germany.
Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich at the University of Tübingen, Tübingen, Germany.
Transpl Infect Dis. 2020 Apr;22(2):e13228. doi: 10.1111/tid.13228. Epub 2019 Dec 16.
Polyomavirus-associated nephropathy (PVAN) remains a relevant complication following kidney transplantation with allograft loss rates of up to 50%. Reduction in overall immunosuppression is a cornerstone of therapy, whereas no specific antiviral regimen has shown conclusive benefit to date. The present case series demonstrates the efficacy of a dual therapeutic approach with low-dose cidofovir and conversion to mTOR-based immunosuppression in PVAN.
Patients with biopsy-proven PVAN having received low-dose cidofovir (0.25 mg/kg) according to the Tübingen Cidofovir Protocol and been converted to mTOR-based immunosuppression were analyzed retrospectively.
Twenty-three patients with a median follow-up of 2.24 [IQR 1.55-5.01] years were included in the analysis. Median time to PVAN diagnosis was 268 [IQR 153-869] days after transplantation. Polyomavirus clearance from plasma was achieved in 78% of patients after a median of 118 [IQR 76-293] days. Of the 23 patients, nine patients (39%) lost their allograft function during follow-up, but only three of these (13%) due to PVAN. Fourteen patients (61%) stabilized or improved allograft function. The cidofovir protocol allowed for specific antiviral therapy without adverse nephrotoxicity, even in patients with low allograft function.
Low-dose cidofovir and conversion to mTOR-based immunosuppression allow for effective virus clearance and preservation of allograft function in a high proportion of patients with PVAN and progressive allograft dysfunction and may prolong allograft survival in these patients.
多瘤病毒相关性肾病（PVAN）仍是肾移植术后的一种相关并发症，移植肾丢失率高达50%。降低整体免疫抑制是治疗的基石，而迄今为止尚无特定的抗病毒方案显示出确凿的益处。本病例系列证明了低剂量西多福韦与转换为基于mTOR的免疫抑制的双重治疗方法在PVAN中的疗效。
对根据图宾根西多福韦方案接受低剂量西多福韦（0.25mg/kg）并转换为基于mTOR的免疫抑制的经活检证实为PVAN的患者进行回顾性分析。
分析纳入了23例患者，中位随访时间为2.24[四分位间距1.55 - 5.01]年。PVAN诊断的中位时间为移植后268[四分位间距153 - 869]天。78%的患者在中位118[四分位间距76 - 293]天后血浆中的多瘤病毒清除。在这23例患者中，9例（39%）在随访期间移植肾功能丧失，但其中仅3例（13%）是由于PVAN。14例（61%）患者移植肾功能稳定或改善。即使在移植肾功能低下的患者中，西多福韦方案也允许进行特异性抗病毒治疗而无不良肾毒性。
低剂量西多福韦和转换为基于mTOR的免疫抑制可使大部分PVAN和移植肾功能进行性减退的患者有效清除病毒并保留移植肾功能，并可能延长这些患者的移植肾存活时间。
