Polyomavirus Nephropathy in ABO Blood Group-Incompatible Kidney Transplantation: Torque Teno Virus and Immunosuppressive Burden as an Approximation to the Problem

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Introduction Earlier reports suggest that patients after ABO-incompatible kidney transplantation (ABOi) are at enhanced risk to develop BK-virus (BKV) 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 HLA-incompatible (HLAi, i.e. pre-transplant donor-specific antibody-positive) and standard-risk transplant recipients. Methods Our retrospective study screened 2256 consecutive kidney transplantations performed between 2007-2020 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- and BKV-PCR was carried out at pre-defined timepoints and ranged from pre-transplant until month 24 post-transplantation. 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 three (median 1.5x10 9 vs. 2.4x10 8 vs. 9.1x10 7 , p=0.010) and month six (3.1x10 9 vs. 1.4x10 7 vs. 6.4x10 7 , p=0.014) post-transplantation. Tacrolimus exposure was significantly higher in ABOi patients compared to HLAi and control patients (ABOi vs. HLAi: p=0.007, ABOi vs. controls: p<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%, p=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.

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