title: Association of Baseline Viral Serology and Sirolimus Regimens With Kidney Transplant Outcomes: A 14-Year Registry-Based Cohort Study in the United States.
abstract: BACKGROUND
  The risks for transplant outcomes associated with baseline viral serostatus in kidney transplant recipients (KTR) on sirolimus have not been widely studied.
  
  
  METHODS
  We performed a cohort-study of 61 590 adult KTR in 2000 to 2013. We used Cox regression models to determine the adjusted hazard ratio (aHR) of patient death, death-censored graft loss and posttransplant malignancy associated with the baseline serostatus (+ or -: hepatitis B core [HBc], hepatitis C virus [HCV], Epstein-Barr virus [EBV], or cytomegalovirus [CMV]) in KTR on sirolimus (SRL) + mycophenolate (MPA) or SRL + tacrolimus (Tac), relative to the control-regimen: Tac + MPA.
  
  
  RESULTS
  Compared with Tac + MPA, SRL + MPA, and SRL + Tac were associated with higher risks of 5-year mortality (aHR, 1.41; 95% CI, 1.23-1.60 and aHR, 1.59; 95% CI, 1.38-1.83, respectively) and death-censored graft loss (aHR, 1.41; 95% CI, 1.24-1.60 and aHR, 1.38; 95% CI, 1.21-1.57, respectively). In KTR with negative pretransplant EBV, CMV, HBc, or HCV serostatus, SRL + MPA not SRL + Tac was associated with a lower risk of posttransplant malignancy compared with control (aHR, 0.27; 95% CI, 0.10-0.72; aHR, 0.61; 95% CI, 0.43-0.88; aHR, 0.79; 95% CI, 0.64-0.97; and aHR, 0.80; 95% CI, 0.65-0.98, respectively, for SRL + MPA and aHR, 0.98: 95% CI, 0.52-1.80; aHR, 0.69; 95% CI, 0.46-1.06; aHR, 0.83; 95% CI, 0.66-1.06 and aHR, 0.85; 95% CI, 0.67-1.07, respectively, for SRL + Tac). In KTR with positive serostatus to any of the above viruses, SRL + MPA or SRL + Tac was not associated with a different malignancy risk compared with control.
  
  
  CONCLUSIONS
  Compared with Tac + MPA, SRL regimens were associated with higher risks for patient death and graft loss, although SRL + MPA was associated with a lower risk for posttransplant malignancy in kidney allograft recipients with negative pretransplant HBc, HCV, EBV, or CMV serology.
authors.affiliation: 1 Division of Nephrology, Hypertension and Renal Transplantation, Department of Medicine, College of Medicine, University of Florida, Gainesville, FL.
authors.forename: Alfonso H
authors.initials: AH
authors.lastname: Santos
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Casey
authors.forename: Wen
authors.initials: W
authors.lastname: Xuerong
authors.forename: Karl L
authors.initials: KL
authors.lastname: Womer
mesh_terms: D000328:Adult; D064591:Allografts; D000914:Antibodies, Viral / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D016009:Chi-Square Distribution; D003586:Cytomegalovirus Infections / Q000097:blood / Q000175:diagnosis / Q000276:immunology* / Q000401:mortality; D004359:Drug Therapy, Combination; D020031:Epstein-Barr Virus Infections / Q000097:blood / Q000175:diagnosis / Q000276:immunology* / Q000401:mortality; D005260:Female; D006085:Graft Survival / Q000187:drug effects; D006509:Hepatitis B / Q000097:blood / Q000175:diagnosis / Q000276:immunology* / Q000401:mortality; D006526:Hepatitis C / Q000097:blood / Q000175:diagnosis / Q000276:immunology* / Q000401:mortality; D006801:Humans; D016867:Immunocompromised Host; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D016030:Kidney Transplantation / Q000009:adverse effects / Q000401:mortality; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009369:Neoplasms / Q000209:etiology; D016017:Odds Ratio; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D012042:Registries; D012189:Retrospective Studies; D012307:Risk Factors; D012698:Serologic Tests; D020123:Sirolimus / Q000009:adverse effects / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome; D014481:United States
chemical_list: D000914:Antibodies, Viral; D015415:Biomarkers; D007166:Immunosuppressive Agents; D020123:Sirolimus