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

Clin Transplant. 2024 May;38(5):e15329. doi: 10.1111/ctr.15329.

Abstract

Background: Immunosuppression 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.

Methods: This 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.

Results: At 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.

Conclusions: Recipients 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.

Keywords: HLA eplet mismatch; T‐cell mediated rejection; alloimmune risk; antibody‐mediated rejection; biopsy‐proven acute rejection; death‐censored graft survival; donor specific antibody; graft survival; kidney transplant; polyoma virus.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • BK Virus* / immunology
  • BK Virus* / isolation & purification
  • Female
  • Follow-Up Studies
  • Glomerular Filtration Rate
  • Graft Rejection* / etiology
  • Graft Rejection* / immunology
  • Graft Survival*
  • Humans
  • Immunosuppressive Agents / adverse effects
  • Immunosuppressive Agents / therapeutic use
  • Kidney Diseases / immunology
  • Kidney Diseases / surgery
  • Kidney Diseases / virology
  • Kidney Failure, Chronic / immunology
  • Kidney Failure, Chronic / surgery
  • Kidney Function Tests*
  • Kidney Transplantation* / adverse effects
  • Male
  • Middle Aged
  • Polyomavirus Infections* / complications
  • Polyomavirus Infections* / immunology
  • Polyomavirus Infections* / virology
  • Postoperative Complications
  • Prognosis
  • Retrospective Studies
  • Risk Factors
  • Transplant Recipients
  • Tumor Virus Infections* / immunology
  • Tumor Virus Infections* / virology
  • Viremia* / immunology
  • Viremia* / virology

Substances

  • Immunosuppressive Agents

Grants and funding