title: Sirolimus therapy predisposes to new-onset diabetes mellitus after renal transplantation: a long-term analysis of various treatment regimens.
abstract: OBJECTIVE
  This retrospective analysis evaluated the impacts of sirolimus (SRL), cyclosporine (CsA), and steroids (S) on the occurrence, treatment, and complications of new-onset diabetes after transplantation (NODAT).
  
  
  METHODS
  We compared 4 groups: group 1, SRL plus full-exposure CsA/S (n = 118); group 2, full-exposure CsA/S/no SRL ± antiproliferative drug (n = 141); group 3, SRL plus reduced CsA exposure/S (n = 212); and group 4, no SRL/full-exposure CsA/S ± antiproliferative drug (n = 43).
  
  
  RESULTS
  NODAT rates reflected the level of CsA exposure; at 10 years 54% versus 30% for groups 1 versus 2 (P = .0001); at 5 years 30% versus 21% for Groups 3 versus 4 (P = .3); 81% of cases were detected within 1 year. The lower NODAT rate in group 3 reflected a benefit of reduced CsA exposure (P = .02; hazard ratio (HR), 1.006). Group 1 showed higher CsA (P = .0001) and lower SRL concentrations (P = .016) versus group 3. CsA exposure closely correlating with NODAT among group 1 (P = .0001) was the major difference between groups 1 and 3 (P = .04; HR, 0.97). Differences in steroid treatment did not play a significant role in NODAT. Comparing groups 1 and 2, SRL was an independent risk factor for NODAT (P = .004; HR, 3.5).
  
  
  CONCLUSIONS
  Our 10-year experience revealed SRL to be an etiologic agent for NODAT, displaying interactive, possibly pharmacokinetic, and pharmacodynamic effects with concomitant CsA in combination treatment.
authors.affiliation: Division of Immunology and Organ Transplantation, University of Texas Medical School, Houston, Texas 77030, USA.
authors.forename: E
authors.initials: E
authors.lastname: Gyurus
authors.forename: Z
authors.initials: Z
authors.lastname: Kaposztas
authors.forename: B D
authors.initials: BD
authors.lastname: Kahan
mesh_terms: D003920:Diabetes Mellitus / Q000139:chemically induced*; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D016030:Kidney Transplantation; D020123:Sirolimus / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D007166:Immunosuppressive Agents; D020123:Sirolimus