Association between cytomegalovirus viremia and long-term outcomes in lung transplant recipients

Mitsuaki Kawashima, Jin Ma, Ella Huszti, Liran Levy, Gregory Berra, Benjamin Renaud-Picard, Akihiro Takahagi, Rasheed Ghany, Masaaki Sato, Shaf Keshavjee, Lianne Singer, Shahid Husain, Deepali Kumar, Jussi Tikkanen, Tereza Martinu*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Although cytomegalovirus (CMV) viremia/DNAemia has been associated with reduced survival after lung transplantation, its association with chronic lung allograft dysfunction (CLAD) and its phenotypes is unclear. We hypothesized that, in a modern era of CMV prophylaxis, CMV DNAemia would still remain associated with death, but also represent a risk factor for CLAD and specifically restrictive allograft syndrome (RAS)/mixed phenotype. This was a single-center retrospective cohort study of all consecutive adult, first, bilateral-/single-lung transplants done between 2010-2016, consisting of 668 patients. Risks for death/retransplantation, CLAD, or RAS/mixed, were assessed by adjusted cause-specific Cox proportional-hazards models. CMV viral load (VL) was primarily modeled as a categorical variable: undetectable, detectable to 999, 1000 to 9999, and ≥10 000 IU/mL. In multivariable models, CMV VL was significantly associated with death/retransplantation (≥10 000 IU/mL: HR = 2.65 [1.78-3.94]; P < .01), but was not associated with CLAD, whereas CMV serostatus mismatch was (D+R–: HR = 2.04 [1.30-3.21]; P < .01). CMV VL was not associated with RAS/mixed in univariable analysis. Secondary analyses with a 7-level categorical or 4-level ordinal CMV VL confirmed similar results. In conclusion, CMV DNAemia is a significant risk factor for death/retransplantation, but not for CLAD or RAS/mixed. CMV serostatus mismatch may have an impact on CLAD through a pathway independent of DNAemia.

Original languageEnglish
Pages (from-to)1057-1069
Number of pages13
JournalAmerican Journal of Transplantation
Volume24
Issue number6
DOIs
StatePublished - Jun 2024
Externally publishedYes

Funding

FundersFunder number
APCBio Innovations, Inc
Sanofi , Inc
Sanofi, Inc
Merck
Roche Italia

    Keywords

    • bronchiolitis obliterans
    • cytomegalovirus
    • graft rejection
    • lung transplantation
    • transplantation immunology

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