Risk factors for progression from low level BK dnaemia to unfavorable outcomes after BK management via immunosuppressive reduction

Abish Kharel, Arjang Djamali, Margaret R. Jorgenson, Beyann Alzoubi, Kurtis J. Swanson, Neetika Garg, Fahad Aziz, Maha A. Mohamed, Didier A. Mandelbrot, Sandesh Parajuli

Research output: Contribution to journalArticlepeer-review

Abstract

Backgrounds: Effective management of BK viremia (BKPyV-DNAemia) in kidney transplant recipients (KTRs) involves regular monitoring and adjustment of immunosuppression. With this strategy, the majority of patients will clear BK or have ongoing, but non-significant, low-level BKPyV-DNAemia. However, despite adjustments, some will develop more severe sequelae of BK including BKPyV-DNAemia >5 log10 copies/mL and BK nephropathy, and others may develop de novo DSA (dnDSA) or acute rejection (AR). Methods: This was a single-center study of KTRs transplanted at the University of Wisconsin-Madison between 01/01/2015 and 12/31/2017. In this study, we sought to elucidate characteristics associated with the progression of BKPyV-DNAemia to unfavorable outcomes after decreasing immunosuppressive medications for the management of BK viremia as described in consensus guidelines. Results: A total of 224 KTRs fulfilled our selection criteria; 118 (53%) resolved or had persistent low DNAemia, 64 (28%) had severe BK/nephropathy, and 42 (19%) developed dnDSA or AR. In multivariable analysis, female gender (HR: 2.05; 95% CI: 1.08-3.90; P =.02); previous rejection (HR: 2.90; 95% CI: 1.04-8.12; P =.04), and early infection (HR: 0.81; 95% CI: 0.72-0.90; P <.001) were associated with the development of severe BK/nephropathy. Conversely, non-depleting induction at transplant (HR: 2.06; 95% CI: 1.03-4.11; P =.03), HLA mismatches >3 (HR: 2.27; HR: 1.01-5.06; P =.04), and delayed graft function (HR: 4.14; 95% CI: 1.12-15.28; P =.03) were associated with development of dnDSA and/or rejection. Conclusion: Our study suggests that almost half of KTRs with BKPyV-DNAemia managed by our immunosuppressant adjustment protocol progress unfavorably. Identification of these risk factors could assist the frontline clinician in creating an individualized immunosuppressive modification plan potentially mitigating negative outcomes.

Original languageEnglish (US)
Article numbere13561
JournalTransplant Infectious Disease
Volume23
Issue number3
DOIs
StatePublished - Jun 2021
Externally publishedYes

Bibliographical note

Funding Information:
Didier A. Mandelbrot is a recipient of unrestricted grant funds from Virginia Lee Cook Foundation which supports this study. The authors thank Ms Dana Clark, MA, for her editorial assistance.

Publisher Copyright:
© 2021 Wiley Periodicals LLC

Keywords

  • BK nephropathy
  • BK viremia
  • denovo DSA
  • rejection

PubMed: MeSH publication types

  • Journal Article

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