title: Doubling of serum creatinine in clinical trials, cost-effectiveness studies, and individual patients: adequate use in renal transplantation.
abstract: BACKGROUND
  The predictive value of doubling of serum creatinine (DSC) has never been assessed in renal transplantation. We evaluated it in terms of its use for clinical trials, cost-effectiveness studies, and individual patients.
  
  
  METHODS
  Retrospective longitudinal study in 896 renal transplant recipients.
  
  
  RESULTS
  Death-censored graft loss occurred in 133 patients, during follow-up (up to 21 years). DSC was a risk factor for graft loss; however, the relative risk was different in patients with glomerular filtration rate less than 40 vs. more than or equal to 40 mL/min (hazard ratio: 14.5 [95% confidence interval: 7.4-28.4] vs. 47.8 [28.4-80.6], P=0.0051). Parameters influencing creatinine value (weight, age, sex) did not modify DSC's predictive value. The use of the composite endpoint DSC or death-censored graft loss instead of death-censored graft loss alone in clinical trials would reduce sample size by 7.1% to 9.0%. The annual probability of DSC to graft loss transition decreased from 76% (follow-up <1 year) to 5% (follow-up ≥10 years). Median graft half-life after DSC was 10 months [95% confidence interval: 6-18] but varied with increasing time to DSC (<1 year: 1 month [0.5-6]; 3-4.9 years: 15 months 5/67) and reference creatinine (<130 μmol/L: 3 months 2/6); ≥130 μmol/L: 25 months 15/37).
  
  
  CONCLUSIONS
  DSC may be adequately used to refine the risk of death-censored graft loss for individual patients. However, the use of DSC as an endpoint in clinical trials marginally affects sample size, and the probability of DSC to graft loss transition is not constant, which limits the use of DSC in cost-effectiveness analyses of renal transplantation.
authors.affiliation: Service de Néphrologie-Immunologie Clinique, Hôpital Bretonneau, CHRU Tours, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Gatault
authors.forename: Azmi
authors.initials: A
authors.lastname: Al-Najjar
authors.forename: Christelle
authors.initials: C
authors.lastname: Barbet
authors.forename: Mélanie
authors.initials: M
authors.lastname: Roland
authors.forename: Inass
authors.initials: I
authors.lastname: Laouad
authors.forename: Matthias
authors.initials: M
authors.lastname: Buchler
authors.forename: Jean-Frédéric
authors.initials: JF
authors.lastname: Marlière
authors.forename: Pierre Emmanuel
authors.initials: PE
authors.lastname: Métais
authors.forename: Alice
authors.initials: A
authors.lastname: Clément
authors.forename: Hubert
authors.initials: H
authors.lastname: Nivet
authors.forename: Yvon
authors.initials: Y
authors.lastname: Lebranchu
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Halimi
mesh_terms: D000328:Adult; D002986:Clinical Trials as Topic / Q000191:economics* / Q000379:methods*; D003362:Cost-Benefit Analysis; D003404:Creatinine / Q000097:blood*; D005260:Female; D005500:Follow-Up Studies; D005919:Glomerular Filtration Rate / Q000502:physiology; D006084:Graft Rejection / Q000097:blood / Q000453:epidemiology / Q000503:physiopathology*; D006801:Humans; D016030:Kidney Transplantation / Q000502:physiology*; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D012189:Retrospective Studies; D012307:Risk Factors; D012680:Sensitivity and Specificity
chemical_list: D003404:Creatinine