title: The impact of viral load and time to onset of cytomegalovirus replication on long-term graft survival after kidney transplantation.
abstract: BACKGROUND
  Asymptomatic cytomegalovirus (CMV) infection is associated with graft dysfunction and failure. However, no study assessed CMV viral load in terms of the risk for graft failure.
  
  
  METHODS
  In a prospective cohort of kidney transplant recipients, we assessed the impact of CMV DNAemia on the overall graft survival and the incidence of moderate-to-severe interstitial fibrosis and tubular atrophy (IF/TA) in protocol biopsy at 36 months. CMV DNAemia was stratified by viral load in whole blood.
  
  
  RESULTS
  A total of 180 patients transplanted from October 2003 through January 2011 were included and followed for 4 years; 87 (48%) patients received 3-month prophylaxis with valacyclovir and 45 (25%) with valganciclovir; 48 (27%) were managed by pre-emptive therapy. Within 12 months of transplantation, CMV DNAemia developed in 102 (57%) patients with 36 (20%) having a viral load of ≥2,000 copies/ml. Multivariate Cox analysis identified CMV DNAemia as an independent risk factor for graft loss (hazard ratio 3.42; P=0.020); however, after stratification by viral load, only CMV DNAemia ≥2,000 copies/ml (hazard ratio 7.62; P<0.001) remained significant. Both early-onset (<3 months; P=0.048) and late-onset (>3 months; P<0.001) CMV DNAemia ≥2,000 copies/ml were risk factors for graft loss. The incidence of moderate-to-severe IF/TA was not significantly influenced by CMV DNAemia.
  
  
  CONCLUSIONS
  Kidney transplant recipients having CMV DNAemia with a higher viral load irrespective of the time to onset are at increased risk for graft loss.
authors.affiliation: Department of Internal Medicine I, Charles University Medical School and Teaching Hospital, Pilsen, Czech Republic.|Biomedical Centre, Faculty of Medicine in Pilsen, Charles University, Pilsen, Czech Republic.
authors.forename: Tomas
authors.initials: T
authors.lastname: Reischig
authors.affiliation: Department of Internal Medicine I, Charles University Medical School and Teaching Hospital, Pilsen, Czech Republic.|Biomedical Centre, Faculty of Medicine in Pilsen, Charles University, Pilsen, Czech Republic.
authors.forename: Martin
authors.initials: M
authors.lastname: Kacer
authors.affiliation: Biomedical Centre, Faculty of Medicine in Pilsen, Charles University, Pilsen, Czech Republic.|Transplant Laboratory, Institute for Clinical and Experimental Medicine, Prague, Czech Republic.
authors.forename: Petra
authors.initials: P
authors.lastname: Hruba
authors.affiliation: Biomedical Centre, Faculty of Medicine in Pilsen, Charles University, Pilsen, Czech Republic.|Department of Hemato-oncology, Charles University Medical School and Teaching Hospital, Pilsen, Czech Republic.
authors.forename: Pavel
authors.initials: P
authors.lastname: Jindra
authors.affiliation: Biomedical Centre, Faculty of Medicine in Pilsen, Charles University, Pilsen, Czech Republic.|Department of Pathology, Charles University Medical School and Teaching Hospital, Pilsen, Czech Republic.
authors.forename: Ondrej
authors.initials: O
authors.lastname: Hes
authors.affiliation: Biomedical Centre, Faculty of Medicine in Pilsen, Charles University, Pilsen, Czech Republic.|Transplant Laboratory, Institute for Clinical and Experimental Medicine, Prague, Czech Republic.
authors.forename: Daniel
authors.initials: D
authors.lastname: Lysak
authors.affiliation: Department of Internal Medicine I, Charles University Medical School and Teaching Hospital, Pilsen, Czech Republic.|Biomedical Centre, Faculty of Medicine in Pilsen, Charles University, Pilsen, Czech Republic.
authors.forename: Mirko
authors.initials: M
authors.lastname: Bouda
authors.affiliation: Biomedical Centre, Faculty of Medicine in Pilsen, Charles University, Pilsen, Czech Republic.|Transplant Laboratory, Institute for Clinical and Experimental Medicine, Prague, Czech Republic.|Department of Nephrology, Institute for Clinical and Experimental Medicine, Prague, Czech Republic.
authors.forename: Ondrej
authors.initials: O
authors.lastname: Viklicky
mesh_terms: D001706:Biopsy; D003587:Cytomegalovirus / Q000502:physiology*; D003586:Cytomegalovirus Infections / Q000175:diagnosis* / Q000209:etiology* / Q000517:prevention & control; D004279:DNA, Viral; D005260:Female; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000276:immunology; D006085:Graft Survival; D006801:Humans; D007677:Kidney Function Tests; D016030:Kidney Transplantation / Q000009:adverse effects*; D008297:Male; D011446:Prospective Studies; D012306:Risk; D013997:Time Factors; D019562:Viral Load; D014766:Viremia; D014779:Virus Replication
chemical_list: D004279:DNA, Viral