title: Low 1-year cyclosporine microemulsion doses are associated with better 5-year renal graft function: an insight from MOST, a multinational observational study.
abstract: BACKGROUND
  In earlier registry analyses, cyclosporine at doses of < 3 mg/kg/d at 1 year post-renal transplantation has been associated with significant graft loss or reduction in renal function. Improvements in cyclosporine formulation with increased bioavailability, plus the use of more efficient comedications, may now confer better outcomes. To determine the effect of the 1-year cyclosporine microemulsion (CsA-ME) dose on renal allograft function at 5 years, we analyzed data collected from 2889 patients with documented graft survival to year 5 in a prospective, multinational, observational study-Neoral MOST.
  
  
  RESULTS
  Glomerular filtration rate (GFR) at year 1 was 63 +/- 20 mL/min and 59 +/- 22 mL/min at year 5. The multivariate analysis including year 1 CsA-ME dose as factor and GFR at 1 year as covariate revealed the most significant factors affecting GFR at year 5 were 1-year GFR, donor age > 60 years, and CsA-ME dose at 1 year. Risk factors associated with reduction in 5-year GFR (<65 mL/min) included donor or recipient age >60 years, delayed graft function, cadaveric donor, previous graft, and acute rejection. CsA-ME dose <3 mg/kg/d was found to protect GFR. Analysis of GFR at each year posttransplantation (Wilcoxon model) found 1-year CsA-ME (cutoff 3 mg/kg/d) had a significant effect at each time point.
  
  
  CONCLUSIONS
  Compared to higher doses, CsA-ME <3 mg/kg/d at year 1 posttransplantation is associated with increased preservation of renal allograft function at year 5.
authors.affiliation: Renal Unit, Careggi University Hospital, Florence, Tuscany, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Salvadori
authors.forename: A
authors.initials: A
authors.lastname: Rosati
authors.forename: E
authors.initials: E
authors.lastname: Bertoni
authors.forename: A
authors.initials: A
authors.lastname: Bock
authors.forename: J
authors.initials: J
authors.lastname: Chapman
authors.forename: B
authors.initials: B
authors.lastname: Dussol
authors.forename: L
authors.initials: L
authors.lastname: Fritsche
authors.forename: V
authors.initials: V
authors.lastname: Kliem
authors.forename: Y
authors.initials: Y
authors.lastname: Lebranchu
authors.forename: F
authors.initials: F
authors.lastname: Oppenheimer
authors.forename: E
authors.initials: E
authors.lastname: Pohanka
authors.forename: G
authors.initials: G
authors.lastname: Tufveson
authors.forename: M
authors.initials: M
authors.lastname: Soergel
mesh_terms: D000368:Aged; D016572:Cyclosporine / Q000008:administration & dosage / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004655:Emulsions; D005500:Follow-Up Studies; D005919:Glomerular Filtration Rate; D006085:Graft Survival / Q000187:drug effects*; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000627:therapeutic use; D016030:Kidney Transplantation / Q000502:physiology*; D016018:Least-Squares Analysis; D008875:Middle Aged; D013997:Time Factors; D014019:Tissue Donors / Q000706:statistics & numerical data
chemical_list: D004655:Emulsions; D007166:Immunosuppressive Agents; D016572:Cyclosporine