Association of BKV viremia and nephropathy with adverse alloimmune outcomes in kidney transplant recipients

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Main Authors: Christie Rampersad, Chris Wiebe, Robert Balshaw, Jared Bullard, Ian W. Gibson, Aaron Trachtenberg, James Shaw, Armelle Perez Cortes Villalobos, Martin Karpinski, Aviva Goldberg, Patricia Birk, Maury Pinsk, David N. Rush, Peter W. Nickerson, Julie Ho
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Published: Wiley 2024
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author Christie Rampersad
Chris Wiebe
Robert Balshaw
Jared Bullard
Ian W. Gibson
Aaron Trachtenberg
James Shaw
Armelle Perez Cortes Villalobos
Martin Karpinski
Aviva Goldberg
Patricia Birk
Maury Pinsk
David N. Rush
Peter W. Nickerson
Julie Ho
author_facet Christie Rampersad
Chris Wiebe
Robert Balshaw
Jared Bullard
Ian W. Gibson
Aaron Trachtenberg
James Shaw
Armelle Perez Cortes Villalobos
Martin Karpinski
Aviva Goldberg
Patricia Birk
Maury Pinsk
David N. Rush
Peter W. Nickerson
Julie Ho
Christie Rampersad
Chris Wiebe
Robert Balshaw
Jared Bullard
Ian W. Gibson
Aaron Trachtenberg
James Shaw
Armelle Perez Cortes Villalobos
Martin Karpinski
Aviva Goldberg
Patricia Birk
Maury Pinsk
David N. Rush
Peter W. Nickerson
Julie Ho
collection Wiley Open Access
contents Association of BKV viremia and nephropathy with adverse alloimmune outcomes in kidney transplant recipients Christie Rampersad Chris Wiebe Robert Balshaw Jared Bullard Ian W. Gibson Aaron Trachtenberg James Shaw Armelle Perez Cortes Villalobos Martin Karpinski Aviva Goldberg Patricia Birk Maury Pinsk David N. Rush Peter W. Nickerson Julie Ho Clinical Transplantation AbstractBackgroundImmunosuppression reduction for BK polyoma virus (BKV) must be balanced against risk of adverse alloimmune outcomes. We sought to characterize risk of alloimmune events after BKV within context of HLA‐DR/DQ molecular mismatch (mMM) risk score.MethodsThis single‐center study evaluated 460 kidney transplant patients on tacrolimus‐mycophenolate‐prednisone from 2010‐2021. BKV status was classified at 6‐months post‐transplant as “BKV” or “no BKV” in landmark analysis. Primary outcome was T‐cell mediated rejection (TCMR). Secondary outcomes included all‐cause graft failure (ACGF), death‐censored graft failure (DCGF), de novo donor specific antibody (dnDSA), and antibody‐mediated rejection (ABMR). Predictors of outcomes were assessed in Cox proportional hazards models including BKV status and alloimmune risk defined by recipient age and molecular mismatch (RAMM) groups.ResultsAt 6‐months post‐transplant, 72 patients had BKV and 388 had no BKV. TCMR occurred in 86 recipients, including 27.8% with BKV and 17% with no BKV (p = .05). TCMR risk was increased in recipients with BKV (HR 1.90, (95% CI 1.14, 3.17); p = .01) and high vs. low‐risk RAMM group risk (HR 2.26 (95% CI 1.02, 4.98); p = .02) in multivariable analyses; but not HLA serological MM in sensitivity analysis. Recipients with BKV experienced increased dnDSA in univariable analysis, and there was no association with ABMR, DCGF, or ACGF.ConclusionsRecipients with BKV had increased risk of TCMR independent of induction immunosuppression and conventional alloimmune risk measures. Recipients with high‐risk RAMM experienced increased TCMR risk. Future studies on optimizing immunosuppression for BKV should explore nuanced risk stratification and may consider novel measures of alloimmune risk. 10.1111/ctr.15329 http://creativecommons.org/licenses/by-nc-nd/4.0/
doi_str_mv 10.1111/ctr.15329
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publisher Wiley
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spellingShingle Association of BKV viremia and nephropathy with adverse alloimmune outcomes in kidney transplant recipients
Christie Rampersad
Chris Wiebe
Robert Balshaw
Jared Bullard
Ian W. Gibson
Aaron Trachtenberg
James Shaw
Armelle Perez Cortes Villalobos
Martin Karpinski
Aviva Goldberg
Patricia Birk
Maury Pinsk
David N. Rush
Peter W. Nickerson
Julie Ho
Clinical Transplantation
Association of BKV viremia and nephropathy with adverse alloimmune outcomes in kidney transplant recipients Christie Rampersad Chris Wiebe Robert Balshaw Jared Bullard Ian W. Gibson Aaron Trachtenberg James Shaw Armelle Perez Cortes Villalobos Martin Karpinski Aviva Goldberg Patricia Birk Maury Pinsk David N. Rush Peter W. Nickerson Julie Ho Clinical Transplantation AbstractBackgroundImmunosuppression reduction for BK polyoma virus (BKV) must be balanced against risk of adverse alloimmune outcomes. We sought to characterize risk of alloimmune events after BKV within context of HLA‐DR/DQ molecular mismatch (mMM) risk score.MethodsThis single‐center study evaluated 460 kidney transplant patients on tacrolimus‐mycophenolate‐prednisone from 2010‐2021. BKV status was classified at 6‐months post‐transplant as “BKV” or “no BKV” in landmark analysis. Primary outcome was T‐cell mediated rejection (TCMR). Secondary outcomes included all‐cause graft failure (ACGF), death‐censored graft failure (DCGF), de novo donor specific antibody (dnDSA), and antibody‐mediated rejection (ABMR). Predictors of outcomes were assessed in Cox proportional hazards models including BKV status and alloimmune risk defined by recipient age and molecular mismatch (RAMM) groups.ResultsAt 6‐months post‐transplant, 72 patients had BKV and 388 had no BKV. TCMR occurred in 86 recipients, including 27.8% with BKV and 17% with no BKV (p = .05). TCMR risk was increased in recipients with BKV (HR 1.90, (95% CI 1.14, 3.17); p = .01) and high vs. low‐risk RAMM group risk (HR 2.26 (95% CI 1.02, 4.98); p = .02) in multivariable analyses; but not HLA serological MM in sensitivity analysis. Recipients with BKV experienced increased dnDSA in univariable analysis, and there was no association with ABMR, DCGF, or ACGF.ConclusionsRecipients with BKV had increased risk of TCMR independent of induction immunosuppression and conventional alloimmune risk measures. Recipients with high‐risk RAMM experienced increased TCMR risk. Future studies on optimizing immunosuppression for BKV should explore nuanced risk stratification and may consider novel measures of alloimmune risk. 10.1111/ctr.15329 http://creativecommons.org/licenses/by-nc-nd/4.0/
title Association of BKV viremia and nephropathy with adverse alloimmune outcomes in kidney transplant recipients
topic Clinical Transplantation
url https://onlinelibrary.wiley.com/doi/10.1111/ctr.15329