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评估在从钙调神经磷酸酶抑制剂转换为贝拉西普的肾移植受者中,细小病毒B19 DNA载量作为预测生物标志物的作用。

Evaluation of Torque Teno Virus DNA Load as a Predictive Biomarker in Kidney Transplant Recipients Converted from Calcineurin Inhibitors to Belatacept.

作者信息

Cabezas Lara, Truffot Aurelie, Germi Raphaele, Bugnazet Mathilde, Malvezzi Paolo, Gnesotto Manon, Rostaing Lionel, Jouve Thomas, Noble Johan

机构信息

Nephrology, Hemodialysis, Apheresis and Kidney Transplantation Department, Université Grenoble Alpes, University Hospital Grenoble, Grenoble, France.

Inserm U 1209, CNRS UMR 5309, Team Epigenetics, Immunity, Metabolism, Cell Signaling and Cancer, Institute for Advanced Biosciences, Université Grenoble Alpes, Grenoble, France.

出版信息

Kidney Int Rep. 2024 Mar 11;9(6):1718-1729. doi: 10.1016/j.ekir.2024.03.006. eCollection 2024 Jun.

Abstract

INTRODUCTION

Belatacept is a relevant alternative to calcineurin inhibitors (CNIs) after kidney transplantation (KT). Circulating Torque Teno virus (TTV) DNA load is correlated to infections and rejection risks post-KT in patients treated with CNIs. The aim of this study was to assess the TTV DNA load profile in kidney transplant recipients converted from CNIs to belatacept and explore its use as a predictive biomarker.

METHODS

Sixty-eight single-center kidney transplanted recipients who were converted from CNIs to belatacept between June, 2015 and December, 2020 were included in this study. Whole blood TTV DNA load was measured before, at 3, 6, and 12 months post-belatacept conversion. Our primary end point was to assess the TTV DNA load profile and correlate the results with rejection and opportunistic infection (OPI).

RESULTS

TTV DNA load remained stable after belatacept conversion, that is, 3.8 (3.1-4.9), 4.4 (3.2-5.4), 4.0 (3.0-5.7) and 4.2 (3.0-5.2) log copies/ml at baseline, 3, 6, and 12 months, respectively. No correlation was found between TTV DNA load and post-KT complications. Chronic allograft dysfunction at 1 year postconversion was associated with a lower TTV DNA load after 6 and 12-months ( = 0.014 and  = 0.021, respectively). A higher TTV DNA load was found in older patients and in those with higher body mass index (BMI) ( = 0.023 and  = 0.005, respectively).

CONCLUSION

Conversion from CNIs to belatacept did not affect TTV DNA load. OPIs or acute rejection occurrences were not associated with TTV DNA load. However, low TTV (lTTV) DNA load after 6 months postconversion may be a promising tool to predict graft dysfunction risk at 1-year postconversion.

摘要

引言

贝拉西普是肾移植(KT)后钙调神经磷酸酶抑制剂(CNI)的一种相关替代药物。在接受CNI治疗的患者中,循环中的细小病毒Torque Teno病毒(TTV)DNA载量与KT后的感染和排斥风险相关。本研究的目的是评估从CNI转换为贝拉西普的肾移植受者的TTV DNA载量谱,并探索其作为预测生物标志物的用途。

方法

本研究纳入了68例在2015年6月至2020年12月期间从CNI转换为贝拉西普的单中心肾移植受者。在转换为贝拉西普前、转换后3个月、6个月和12个月测量全血TTV DNA载量。我们的主要终点是评估TTV DNA载量谱,并将结果与排斥反应和机会性感染(OPI)相关联。

结果

转换为贝拉西普后TTV DNA载量保持稳定,即基线时、3个月、6个月和12个月时分别为3.8(3.1 - 4.9)、4.4(3.2 - 5.4)、4.0(3.0 - 5.7)和4.2(3.0 - 5.2)log拷贝/毫升。未发现TTV DNA载量与KT后并发症之间存在相关性。转换后1年的慢性移植物功能障碍与6个月和12个月后较低的TTV DNA载量相关(分别为P = 0.014和P = 0.021)。在老年患者和体重指数(BMI)较高的患者中发现较高的TTV DNA载量(分别为P = 0.023和P = 0.005)。

结论

从CNI转换为贝拉西普不影响TTV DNA载量。OPI或急性排斥反应的发生与TTV DNA载量无关。然而,转换后6个月时低TTV(lTTV)DNA载量可能是预测转换后1年移植物功能障碍风险的一个有前景的工具。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/34bc/11184384/8aa489d677ba/ga1.jpg

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