title: Concentration-controlled use of sirolimus associated with reduced exposure of cyclosporine in black recipients of primarily living renal allograft donors: 12-month results.
abstract: OBJECTIVE
  This study was designed to identify optimal therapeutic sirolimus (SRL) concentrations in black kidney transplant recipients on reduced cyclosporine (CsA) exposure and prednisone.
  
  
  METHODS
  Seventy patients (64 living/six deceased) received CsA (8-10 mg/kg/d), prednisone, and 15 mg loading dose followed by 5-mg fixed doses of SRL till day 7 when they were randomized to maintain SRL trough concentrations (high-performance liquid chromatography) of 8-12 (GI = 34) or 15-20 (GII = 36) ng/mL.
  
  
  RESULTS
  Mean CsA concentrations were 109 +/- 53 vs. 89 +/- 41 ng/mL and 75 +/- 54 vs. 60 +/- 35 ng/mL (ns) at 2 and 6 months. Accordingly, mean SRL trough concentrations were 12.4 +/- 6.1 vs. 20.0 +/- 9.5 ng/mL (p < 0.001) and 10.8 +/- 5.8 vs. 18.0 +/- 6.1 ng/mL (p < 0.001). The incidence of biopsy-proven acute rejection [13% (GI: 18% vs. GII: 8%, ns)], graft loss or death was 16% (GI: 21% vs. GII: 11%, ns]. There were no deaths and three graft losses (GI = 1; GII = 2). Creatinine clearance was higher in GI (64.5 +/- 17 vs. 54.4 +/- 14.7 mL/min, p = 0.011). The incidence of post-transplant diabetes mellitus was 13% and no CMV disease was observed.
  
  
  CONCLUSIONS
  In black recipients of primarily living renal allograft donors reduced CsA exposure and SRL concentration-controlled regimens produced low incidences of acute rejection, post-transplant diabetes mellitus and CMV disease, with no significant impairment in graft function.
authors.affiliation: Nephrology Division, Hospital do Rim e Hipertensão, Sao Paulo, SP, Brazil.
authors.forename: Alexandra N
authors.initials: AN
authors.lastname: Ferreira
authors.forename: Paula G
authors.initials: PG
authors.lastname: Machado
authors.forename: Cláudia R
authors.initials: CR
authors.lastname: Felipe
authors.forename: Sofia A
authors.initials: SA
authors.lastname: Motegi
authors.forename: Beatriz H
authors.initials: BH
authors.lastname: Hosaka
authors.forename: Márcia K
authors.initials: MK
authors.lastname: Tanaka
authors.forename: Luciana A
authors.initials: LA
authors.lastname: Kamura
authors.forename: Sung I
authors.initials: SI
authors.lastname: Park
authors.forename: Riberto
authors.initials: R
authors.lastname: Garcia
authors.forename: Marcello
authors.initials: M
authors.lastname: Franco
authors.forename: Fernando
authors.initials: F
authors.lastname: Alfieri
authors.forename: Dulci E
authors.initials: DE
authors.lastname: Casarini
authors.forename: Hélio
authors.initials: H
authors.lastname: Tedesco-Silva
authors.forename: José O
authors.initials: JO
authors.lastname: Medina-Pestana
mesh_terms: D000328:Adult; D001741:Black or African American; D001706:Biopsy; D002851:Chromatography, High Pressure Liquid; D016572:Cyclosporine / Q000008:administration & dosage* / Q000493:pharmacokinetics; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D005938:Glucocorticoids / Q000008:administration & dosage / Q000493:pharmacokinetics; D006084:Graft Rejection / Q000097:blood / Q000473:pathology / Q000517:prevention & control*; D006085:Graft Survival; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D007676:Kidney Failure, Chronic / Q000208:ethnology / Q000601:surgery; D016030:Kidney Transplantation; D008297:Male; D011241:Prednisone / Q000008:administration & dosage / Q000493:pharmacokinetics; D011446:Prospective Studies; D020123:Sirolimus / Q000008:administration & dosage* / Q000493:pharmacokinetics; D013997:Time Factors; D014184:Transplantation, Homologous; D016896:Treatment Outcome
chemical_list: D005938:Glucocorticoids; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D011241:Prednisone; D020123:Sirolimus