TY - JOUR
T1 - Association between cytomegalovirus viremia and long-term outcomes in lung transplant recipients
AU - Kawashima, Mitsuaki
AU - Ma, Jin
AU - Huszti, Ella
AU - Levy, Liran
AU - Berra, Gregory
AU - Renaud-Picard, Benjamin
AU - Takahagi, Akihiro
AU - Ghany, Rasheed
AU - Sato, Masaaki
AU - Keshavjee, Shaf
AU - Singer, Lianne
AU - Husain, Shahid
AU - Kumar, Deepali
AU - Tikkanen, Jussi
AU - Martinu, Tereza
N1 - Publisher Copyright:
© 2024 The Authors
PY - 2024/6
Y1 - 2024/6
N2 - 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.
AB - 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.
KW - bronchiolitis obliterans
KW - cytomegalovirus
KW - graft rejection
KW - lung transplantation
KW - transplantation immunology
UR - http://www.scopus.com/inward/record.url?scp=85186089399&partnerID=8YFLogxK
U2 - 10.1016/j.ajt.2024.01.027
DO - 10.1016/j.ajt.2024.01.027
M3 - ???researchoutput.researchoutputtypes.contributiontojournal.article???
C2 - 38307417
AN - SCOPUS:85186089399
SN - 1600-6135
VL - 24
SP - 1057
EP - 1069
JO - American Journal of Transplantation
JF - American Journal of Transplantation
IS - 6
ER -