ABO血型不相容肾移植中的多瘤病毒肾病：细小病毒与免疫抑制负担对该问题的一种近似考量
Polyomavirus Nephropathy in ABO Blood Group-Incompatible Kidney Transplantation: Torque Teno Virus and Immunosuppressive Burden as an Approximation to the Problem.
作者信息
Eder Michael, Schrag Tarek A, Havel Ella F, Kainz Alexander, Omic Haris, Doberer Konstantin, Kozakowski Nicolas, Körmöczi Günther F, Schönbacher Marlies, Fischer Gottfried, Strassl Robert, Breuer Monika, Weseslindtner Lukas, Haupenthal Frederik, Böhmig Georg A, Puchhammer-Stöckl Elisabeth, Bond Gregor, Görzer Irene, Eskandary Farsad
机构信息
Division of Nephrology and Dialysis, Department of Medicine III, Medical University of Vienna, Vienna, Austria.
Department of Pathology, Medical University of Vienna, Vienna, Austria.
出版信息
Kidney Int Rep. 2024 Apr 3;9(6):1730-1741. doi: 10.1016/j.ekir.2024.04.003. eCollection 2024 Jun.
INTRODUCTION
Earlier reports suggest that patients after ABO-incompatible kidney transplantation (ABOi) are at enhanced risk of developing BK-virus (BKV, also known as BK polyomavirus [BKPyV]) nephropathy (BKPyVAN). It remains elusive whether this is a result of more intense immunosuppression or an ABOi-associated "intrinsic attribute." To address this question, we measured Torque Teno virus (TTV) loads as a quantitative proxy for immunosuppressive depth in ABOi recipients and compared them to human leukocyte antigen-incompatible (HLAi, i.e. pretransplant donor-specific antibody-positive) and standard-risk transplant recipients.
METHODS
Our retrospective study screened 2256 consecutive kidney transplantations performed between 2007 and 2020 at the Medical University of Vienna. Out of 629 in-principle eligible transplantations, we were able to include 465 patients: 42 ABOi, 106 HLAi, and 317 control recipients. Longitudinal TTV- polymerase chain reaction (PCR) and BKV-PCR was carried out at predefined timepoints and ranged from pretransplant until month 24 posttransplantation. TTV loads and immunosuppression were evaluated in the context of BKV-associated complications.
RESULTS
ABOi recipients had a higher TTV load compared to HLAi and controls both at month 3 (median 1.5 × 10 vs. 2.4 × 10 vs. 9.1 × 10; = 0.010) and at month 6 (3.1 × 10 vs. 1.4 × 10 vs. 6.4 × 10; = 0.014) posttransplantation. Tacrolimus exposure was significantly higher in ABOi patients compared to HLAi and control patients (ABOi vs. HLAi: = 0.007; ABOi vs. controls: < 0.0001). Biopsy-proven BKPyVAN was more frequent in ABOi recipients when compared to HLAi and control recipients (11.9% vs. 2.8% vs. 4.1%; = 0.046).
CONCLUSION
Our data support the assumption that ABOi patients are indeed at higher risk to develop BKPyVAN. A higher TTV load and immunosuppressive burden suggest that intense immunosuppression, rather than an "intrinsic attribute" conferred by ABOi, may contribute to this finding.
引言
早期报告表明，ABO血型不相容肾移植（ABOi）后的患者发生BK病毒（BKV，也称为BK多瘤病毒[BKPyV]）肾病（BKPyVAN）的风险增加。这是由于更强的免疫抑制作用还是ABOi相关的“内在属性”，目前尚不清楚。为了解决这个问题，我们测量了ABOi受者中Torque Teno病毒（TTV）载量，作为免疫抑制深度的定量指标，并将其与人类白细胞抗原不相容（HLAi，即移植前供体特异性抗体阳性）和标准风险移植受者进行比较。
方法
我们的回顾性研究筛查了2007年至2020年在维也纳医科大学进行的2256例连续肾移植。在629例原则上符合条件的移植中，我们纳入了465例患者：42例ABOi受者、106例HLAi受者和317例对照受者。在预定时间点进行纵向TTV聚合酶链反应（PCR）和BKV-PCR，范围从移植前到移植后24个月。在BK病毒相关并发症的背景下评估TTV载量和免疫抑制情况。
结果
与HLAi受者和对照受者相比，ABOi受者在移植后第3个月（中位数分别为1.5×10 vs. 2.4×10 vs. 9.1×10；P = 0.010）和第6个月（3.1×10 vs. 1.4×10 vs. 6.4×10；P = 0.014）时TTV载量更高。与HLAi受者和对照受者相比，ABOi患者的他克莫司暴露量显著更高（ABOi与HLAi相比：P = 0.007；ABOi与对照相比：P < 0.0001）。与HLAi受者和对照受者相比，经活检证实的BKPyVAN在ABOi受者中更常见（11.9% vs. 2.8% vs. 4.1%；P = 0.046）。
结论
我们的数据支持这样的假设，即ABOi患者确实发生BKPyVAN的风险更高。更高的TTV载量和免疫抑制负担表明，强烈的免疫抑制而非ABOi赋予的“内在属性”可能导致了这一结果。
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