title: Sirolimus-based therapy following early cyclosporine withdrawal provides significantly improved renal histology and function at 3 years.
abstract: Graft function and histology are predictive of renal transplant survival. The Rapamune Maintenance Regimen study demonstrated that early cyclosporine (CsA) withdrawal from a sirolimus (SRL)-CsA-steroid (ST) regimen improved renal function and blood pressure. We report the protocol-mandated biopsy findings from that study. Renal transplant patients (n = 430) receiving SRL-CsA-ST were randomized at 3 months after transplantation to remain on SRL-CsA-ST, or to have CsA withdrawn (SRL-ST group). Protocol-mandated biopsies were performed at engraftment and at 12 and 36 months. Two pathologists blindly evaluated 484 biopsies to obtain the Chronic Allograft Damage Index (CADI) scores. At 36 months among patients with serial biopsies (n = 63), the mean CADI score was significantly lower with SRL-ST(4.70 vs. 3.20, p = 0.003), as was the mean tubular atrophy score (0.77 vs. 0.32, p < 0.001). All six components of the CADI score were numerically lower in SRL-ST group; moreover, inflammation and the tubular atrophy scores decreased significantly in the SRL-ST group between 12 and 36 months. The calculated glomerular filtration rate at 36 months was significantly better in the CsA-withdrawal group (54.8 vs. 68.2 mL/min, p = 0.009). In conclusion, withdrawing CsA from the SRL-CsA-ST regimen resulted in improved renal histology and function.
authors.affiliation: Hospitais da Universidade de Coimbra, Coimbra, Portugal. afmota@iol.pt
authors.forename: Alfredo
authors.initials: A
authors.lastname: Mota
authors.forename: Manuel
authors.initials: M
authors.lastname: Arias
authors.forename: Eero I
authors.initials: EI
authors.lastname: Taskinen
authors.forename: Timo
authors.initials: T
authors.lastname: Paavonen
authors.forename: Yves
authors.initials: Y
authors.lastname: Brault
authors.forename: Christophe
authors.initials: C
authors.lastname: Legendre
authors.forename: Kerstin
authors.initials: K
authors.lastname: Claesson
authors.forename: Marco
authors.initials: M
authors.lastname: Castagneto
authors.forename: Josep M
authors.initials: JM
authors.lastname: Campistol
authors.forename: Brian
authors.initials: B
authors.lastname: Hutchison
authors.forename: James T
authors.initials: JT
authors.lastname: Burke
authors.forename: Sedar
authors.initials: S
authors.lastname: Yilmaz
authors.forename: Pekka
authors.initials: P
authors.lastname: Häyry
authors.forename: John F
authors.initials: JF
authors.lastname: Neylan
mesh_terms: D000328:Adult; D001706:Biopsy; D001794:Blood Pressure; D016572:Cyclosporine / Q000627:therapeutic use*; D005260:Female; D005919:Glomerular Filtration Rate; D006084:Graft Rejection / Q000517:prevention & control; D006085:Graft Survival / Q000187:drug effects*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007668:Kidney / Q000187:drug effects / Q000502:physiology; D016030:Kidney Transplantation / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D020123:Sirolimus / Q000627:therapeutic use*; D013256:Steroids / Q000627:therapeutic use; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D007166:Immunosuppressive Agents; D013256:Steroids; D016572:Cyclosporine; D020123:Sirolimus