title: Critical analysis of valganciclovir dosing and renal function on the development of cytomegalovirus infection in kidney transplantation.
abstract: BACKGROUND
  Cytomegalovirus (CMV) infection is one of the most common and important opportunistic infections following kidney transplantation. It causes significant morbidity and mortality. Valganciclovir (VGCV) is the drug of choice for prophylaxis to prevent CMV infection.
  
  
  METHODS
  We conducted a post-hoc analysis of a randomized controlled trial in 187 kidney transplant recipients to evaluate the impact of VGCV dosing and renal function on the development of CMV infection.
  
  
  CONCLUSIONS
  The results demonstrate that the following variables were independent risk factors for the development of CMV infection: high-risk CMV serostatus (donor positive/recipient negative; hazard ratio [HR] 1.4, 95% confidence interval [CI] 1.46-5.28, P = 0.002); anti-thymocyte globulin induction therapy (HR 2.1, 95% CI 1.08-4.07, P = 0.028); higher mean tacrolimus trough concentration (HR 1.4, 95% CI 1.09-1.74, P = 0.007); creatinine clearance <60 mL/min (HR 3.4, 95% CI 1.64-6.85, P = 0.001); and body weight >80 kg (HR 2.1, 95% CI 1.05-4.37, P = 0.037). VGCV dosing was appropriate for most patients, in those who did and did not develop CMV infection. These results strongly suggest that the currently recommended dose adjustments of VGCV dosing based on estimated renal function calculated using ideal body weight may underestimate the renal function of overweight patients and indirectly result in underexposure of overweight patients to VGCV. Based on these findings, further VGCV pharmacokinetic analyses are warranted in kidney transplant recipients with moderate-to-severe renal dysfunction.
authors.affiliation: Department of Medicine, Division of Nephrology and Hypertension, Medical University of South Carolina, Charleston, South Carolina, USA.
authors.forename: M A
authors.initials: MA
authors.lastname: Posadas Salas
authors.forename: D J
authors.initials: DJ
authors.lastname: Taber
authors.forename: E
authors.initials: E
authors.lastname: Chua
authors.forename: N
authors.initials: N
authors.lastname: Pilch
authors.forename: K
authors.initials: K
authors.lastname: Chavin
authors.forename: B
authors.initials: B
authors.lastname: Thomas
mesh_terms: D000328:Adult; D000368:Aged; D000914:Antibodies, Viral / Q000097:blood*; D000961:Antilymphocyte Serum / Q000627:therapeutic use; D000998:Antiviral Agents / Q000008:administration & dosage*; D001835:Body Weight; D003404:Creatinine / Q000097:blood / Q000652:urine; D003587:Cytomegalovirus / Q000276:immunology*; D003586:Cytomegalovirus Infections / Q000097:blood / Q000517:prevention & control*; D018572:Disease-Free Survival; D005260:Female; D015774:Ganciclovir / Q000008:administration & dosage / Q000031:analogs & derivatives*; D006801:Humans; D007166:Immunosuppressive Agents / Q000097:blood / Q000627:therapeutic use; D007668:Kidney / Q000502:physiology*; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D016559:Tacrolimus / Q000097:blood; D000077562:Valganciclovir
chemical_list: D000914:Antibodies, Viral; D000961:Antilymphocyte Serum; D000998:Antiviral Agents; D007166:Immunosuppressive Agents; D003404:Creatinine; D000077562:Valganciclovir; D015774:Ganciclovir; D016559:Tacrolimus
keywords: cytomegalovirus infection; renal function; valganciclovir