title: Preservation of graft function in low-risk living kidney transplant recipients treated with a combination of sirolimus and cyclosporine.
abstract: The use of sirolimus (SRL) in combination with full doses of cyclosporin A (CsA) results in reduced one-year kidney allograft function, which is associated with shorter long-term allograft survival. We determined the effect of reduced CsA exposure on graft function in patients receiving SRL and prednisone. Ninety recipients of living kidney transplants receiving SRL (2 mg/day, po) were compared to 35 recipients receiving azathioprine (AZA, 2 mg kg-1 day-1, po). All patients also received CsA (8-10 mg kg-1 day-1, po) and prednisone (0.5 mg kg-1 day-1). Efficacy end-point was a composite of biopsy-confirmed acute rejection, graft loss, or death at one year. Graft function was measured by creatinine, creatinine clearance, and graft function deterioration between 3 and 12 months (delta1/Cr). CsA concentrations in patients receiving SRL were 26% lower. No differences in one-year composite efficacy end-point were observed comparing SRL and AZA groups (18 vs 20%) or in the incidence of biopsy-proven acute rejection (14.4 and 14.3%). There were no differences in mean +/- SD creatinine (1.65 +/- 0.46 vs 1.60 +/- 0.43 mg/dl, P = 0.48) or calculated creatinine clearances (61 +/- 15 vs 62 +/- 13 ml/min, P = 0.58) at one year. Mean +/- SD delta1/Cr (-11 +/- 17 vs -14 +/- 15%, P = 0.7) or the percentage of patients with >20% (26 vs 31%, P = 0.6) or >30% delta1/Cr (19 vs 17%, P = 1) did not differ between the two groups. The use of 2-mg fixed oral doses of SRL and reduced CsA exposure was effective in preventing acute rejection and preserving allograft function.
authors.affiliation: Divisão de Nefrologia, Hospital do Rim e Hipertensão, Universidade Federal de São Paulo, Brasil.
authors.forename: P G P
authors.initials: PG
authors.lastname: Machado
authors.forename: C R
authors.initials: CR
authors.lastname: Felipe
authors.forename: S I
authors.initials: SI
authors.lastname: Park
authors.forename: R
authors.initials: R
authors.lastname: Garcia
authors.forename: S
authors.initials: S
authors.lastname: Moreira
authors.forename: D
authors.initials: D
authors.lastname: Casarini
authors.forename: M
authors.initials: M
authors.lastname: Franco
authors.forename: F
authors.initials: F
authors.lastname: Alfieri
authors.forename: H
authors.initials: H
authors.lastname: Tedesco-Silva
authors.forename: J O
authors.initials: JO
authors.lastname: Medina-Pestana
mesh_terms: D000293:Adolescent; D000328:Adult; D001379:Azathioprine / Q000008:administration & dosage; D016572:Cyclosporine / Q000008:administration & dosage* / Q000097:blood; D004359:Drug Therapy, Combination; D005260:Female; D006084:Graft Rejection / Q000517:prevention & control*; D006085:Graft Survival / Q000187:drug effects; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000097:blood; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D011241:Prednisone / Q000008:administration & dosage; D020123:Sirolimus / Q000008:administration & dosage* / Q000097:blood; D016896:Treatment Outcome
chemical_list: D007166:Immunosuppressive Agents; D016572:Cyclosporine; D001379:Azathioprine; D011241:Prednisone; D020123:Sirolimus