Cytomegalovirus serology and replication remain associated with solid organ graft rejection and graft loss in the era of prophylactic treatment.
BACKGROUND
Cytomegalovirus (CMV) replication has been associated with more risk for solid organ graft rejection. We wondered whether this association still holds when patients at risk receive prophylactic treatment for CMV.


METHODS
We correlated CMV infection, biopsy-proven graft rejection, and graft loss in 1,414 patients receiving heart (n=97), kidney (n=917), liver (n=237), or lung (n=163) allografts reported to the Swiss Transplant Cohort Study.


RESULTS
Recipients of all organs were at an increased risk for biopsy-proven graft rejection within 4 weeks after detection of CMV replication (hazard ratio [HR] after heart transplantation, 2.60; 95% confidence interval [CI], 1.34-4.94, P<0.001; HR after kidney transplantation, 1.58; 95% CI, 1.16-2.16, P=0.02; HR after liver transplantation, 2.21; 95% CI, 1.53-3.17, P<0.001; HR after lung transplantation, 5.83; 95% CI, 3.12-10.9, P<0.001. Relative hazards were comparable in patients with asymptomatic or symptomatic CMV infection. The CMV donor or recipient serological constellation also predicted the incidence of graft rejection after liver and lung transplantation, with significantly higher rates of rejection in transplants in which donor or recipient were CMV seropositive (non-D-/R-), compared with D- transplant or R- transplant (HR, 3.05; P=0.002 for liver and HR, 2.42; P=0.01 for lung transplants). Finally, graft loss occurred more frequently in non-D- or non-R- compared with D- transplant or R- transplant in all organs analyzed. Valganciclovir prophylactic treatment seemed to delay, but not prevent, graft loss in non-D- or non-R- transplants.


CONCLUSIONS
Cytomegalovirus replication and donor or recipient seroconstellation remains associated with graft rejection and graft loss in the era of prophylactic CMV treatment.
1 Immunotherapy Laboratory, Department of Biomedicine, University Hospital Basel, Switzerland. 2 Infectious Diseases and Hospital Epidemiology, University Hospital, Basel, Switzerland. 3 Transplantation and Clinical Virology, Department of Biomedicine, University of Basel, Basel, Switzerland. 4 Department of Infectious Diseases, University Hospital Bern, Bern, Switzerland. 5 Service of Infectious Diseases, University Hospital, Geneva, Switzerland. 6 Infectious Diseases Service and Transplantation Center, University Hospital (CHUV) and University of Lausanne, Lausanne, Switzerland. 7 Institute of Microbiology and Infectious Diseases Service, University Hospital (CHUV) and University of Lausanne, Lausanne, Switzerland. 8 Division of Infectious Diseases and Hospital Hygiene, Kantonsspital, St. Gallen, Switzerland. 9 Division of Infectious Diseases and Hospital Epidemiology, University Hospital, Switzerland. 10 Clinic for Transplantation Immunology and Nephrology, University Hospital Basel, Switzerland. 11 Address correspondence to: Martin Stern, M.D., Immunotherapy Laboratory, Department of Biomedicine, University Hospital Basel, Hebelstrasse 20 4031, Basel, Switzerland.
Martin
M
Stern
Hans
H
Hirsch
Alexia
A
Cusini
Christian
C
van Delden
Oriol
O
Manuel
Pascal
P
Meylan
Katia
K
Boggian
Nicolas J
NJ
Mueller
Michael
M
Dickenmann
D000293:Adolescent; D000328:Adult; D000368:Aged; D001706:Biopsy; D002648:Child; D002675:Child, Preschool; D003587:Cytomegalovirus / Q000502:physiology; D003586:Cytomegalovirus Infections / Q000097:blood* / Q000503:physiopathology; D005260:Female; D006084:Graft Rejection; D006085:Graft Survival; D016027:Heart Transplantation; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007223:Infant; D007231:Infant, Newborn; D016030:Kidney Transplantation; D016031:Liver Transplantation; D016040:Lung Transplantation; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D011446:Prospective Studies; D013557:Switzerland; D016896:Treatment Outcome; D014779:Virus Replication; D055815:Young Adult
D007166:Immunosuppressive Agents