Probabilistic modeling of cytomegalovirus infection under consensus clinical management guidelines.
BACKGROUND
Cytomegalovirus (CMV) is the most common viral pathogen after renal transplantation and remains a major therapeutic challenge with important clinical and economic implications from both direct and indirect consequences of infection.


METHODS
This 5-year study modeled the relationship between CMV infection and biopsy-proven graft rejection, graft loss, or death after renal transplantation in an inception cohort using Canadian consensus guidelines for CMV management as a component of a detailed cost-analysis of viral infection.


RESULTS
Probabilities of CMV viremia and syndrome/disease among 270 sequential graft recipients were 0.27 and 0.09, respectively; 91% of cases occurred in the first 6 months. Probability of CMV infection as the first event was 0.29, with a probability of subsequent biopsy-proven acute rejection (BPAR) of 0.05 (mean: 62+/-26 days, range: 32-85 days), whereas the probability of BPAR as the first event was 0.18, with a probability of subsequent CMV infection of 0.38 (mean: 63+/-31, range: 27-119 days). Probability of freedom from both CMV infection and BPAR throughout the period of observation was 0.53. Time-dependent Cox analysis showed that neither donor/recipient CMV risk stratum nor CMV infection influenced the risks of BPAR (P=0.24; P=0.74) or of graft loss or death (P=0.26; P=0.34). In contrast, BPAR significantly increased the risk of both subsequent CMV infection (hazard ratio=1.77, P=0.03) and of graft loss or death (hazard ratio=8.31, P<0.0001).


CONCLUSIONS
Although current antiviral therapy seems to mitigate the reported deleterious effects of CMV infection on BPAR or graft survival, BPAR remains a significantly risk factor for both CMV infection and functional graft survival.
Dmitrienko
Svetlana
S
Immunology Laboratory, Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada.
Balshaw
Robert
R
Machnicki
Gerardo
G
Shapiro
R Jean
RJ
Keown
Paul A
PA
D000328:Adult; D000961:Antilymphocyte Serum / Q000627:therapeutic use; D000998:Antiviral Agents / Q000627:therapeutic use; D001706:Biopsy; D003586:Cytomegalovirus Infections / Q000188:drug therapy / Q000453:epidemiology* / Q000473:pathology; D015774:Ganciclovir / Q000627:therapeutic use; D006084:Graft Rejection / Q000473:pathology / Q000821:virology; D006650:Histocompatibility Testing; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D016030:Kidney Transplantation / Q000009:adverse effects* / Q000276:immunology; D011183:Postoperative Complications / Q000453:epidemiology; D017410:Practice Guidelines as Topic; D011336:Probability; D012189:Retrospective Studies; D018570:Risk Assessment; D013601:T-Lymphocytes / Q000276:immunology
D000961:Antilymphocyte Serum; D000998:Antiviral Agents; D007166:Immunosuppressive Agents; D015774:Ganciclovir