title: Risk factors and impact of cytomegalovirus disease in simultaneous pancreas-kidney transplantation.
abstract: BACKGROUND
  The relevance of cytomegalovirus (CMV) in simultaneous pancreas kidney (SPK) transplant recipients in the modern era of immunosuppression and antiviral therapeutics is largely unquantified. We sought to determine the risk factors of CMV disease and its impact on SPK transplant outcomes in recipients all receiving a consistent regime of maintenance immunosuppression and CMV prophylaxis.
  
  
  METHODS
  This is a retrospective, single center study of 100 consecutive SPK transplant recipients. All received maintenance immunosuppression with mycophenolate mofetil, tacrolimus, and prednisone. CMV prophylaxis consisted of a short course of parenteral gancyclovir followed by oral gancyclovir. Recipients at high-risk (D+/R-) for CMV also received CMV hyperimmune globulin. Multivariate analysis of risk factors for CMV disease and risk factors for adverse outcomes in SPK transplantation were determined. The effect of duration of prophylaxis on timing and severity of CMV disease in high-risk (D+/R-) SPK transplant recipients was also evaluated.
  
  
  RESULTS
  The actual 1-year rate of CMV disease was 17.0% (12.0% noninvasive, 5.0% tissue invasive); and according to donor and recipient CMV serological status was: D-/R+: 0%; D-/R-: 2.8%; D+/R+: 25.6%; and D+/R-: 40.6%. Multivariate analysis showed transplantation of organs from a donor with positive CMV serology to be predictive of CMV disease with a relative risk of 63.37 (P=0.0052). In the high-risk (D+/R-) subgroup, the duration of prophylactic therapy delayed onset of CMV disease, but had minimal effect on severity. Invasive CMV disease was an independent predictor of mortality but did not decrease kidney or pancreas allograft survival.
  
  
  CONCLUSIONS
  Outcomes of SPK transplantation have improved in the current era of modern immunosuppression, yet CMV remains an important pathogen. The serological status of the organ donor and the duration of CMV prophylaxis are predictive of who and when CMV disease may occur. Nevertheless, new strategies that reduce risk and severity of CMV disease are still needed.
authors.affiliation: Department of Surgery, Division of Transplantation, Northwestern University Medical School, Chicago, IL 60611, USA.
authors.forename: D B
authors.initials: DB
authors.lastname: Kaufman
authors.forename: J R
authors.initials: JR
authors.lastname: Leventhal
authors.forename: L G
authors.initials: LG
authors.lastname: Gallon
authors.forename: M A
authors.initials: MA
authors.lastname: Parker
authors.forename: A J
authors.initials: AJ
authors.lastname: Koffron
authors.forename: J P
authors.initials: JP
authors.lastname: Fryer
authors.forename: M M
authors.initials: MM
authors.lastname: Abecassis
authors.forename: F P
authors.initials: FP
authors.lastname: Stuart
mesh_terms: D000293:Adolescent; D000328:Adult; D000998:Antiviral Agents / Q000008:administration & dosage / Q000627:therapeutic use; D003586:Cytomegalovirus Infections / Q000453:epidemiology / Q000209:etiology* / Q000517:prevention & control; D004334:Drug Administration Schedule; D005260:Female; D005544:Forecasting; D015774:Ganciclovir / Q000008:administration & dosage / Q000627:therapeutic use; D006801:Humans; D015994:Incidence; D016030:Kidney Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D016035:Pancreas Transplantation / Q000009:adverse effects*; D012307:Risk Factors; D014019:Tissue Donors
chemical_list: D000998:Antiviral Agents; D015774:Ganciclovir