title: Early cyclosporine withdrawal from a sirolimus-based regimen results in better renal allograft survival and renal function at 48 months after transplantation.
abstract: We report the 48-month results of a trial testing whether withdrawal of cyclosporine (CsA) from a sirolimus (SRL)-CsA-steroid (ST) regimen would impact renal allograft survival. Eligible patients receiving SRL-CsA-ST from transplantation were randomly assigned at 3 months to remain on triple therapy (SRL-CsA-ST, n = 215) or to have CsA withdrawn and SRL trough concentrations increased (SRL-ST, n = 215). SRL-ST therapy resulted in significantly better graft survival, either when including death with a functioning graft as an event (84.2% vs. 91.5%, P = 0.024) or when censoring it (90.6% vs. 96.1%, P = 0.026). Calculated glomerular filtration rate (43.8 vs. 58.3 ml/min, P < 0.001) and mean arterial blood pressure (101.3 vs. 97.1 mmHg, P = 0.047) were also improved with SRL-ST. Differences in the incidences of biopsy-proven acute rejection after randomization (6.5% vs. 10.2%, SRL-CsA-ST versus SRL-ST, respectively) and mortality (7.9% vs. 4.7%) were not significant. SRL-CsA-ST-treated patients had significantly higher incidences of adverse events generally associated with CsA, whereas those in the SRL-ST group experienced greater frequencies of events commonly related to higher trough levels of SRL. In conclusion, early withdrawal of CsA from a SRL-CsA-ST regimen rapidly improves renal function and ultimately results in better graft survival.
authors.affiliation: Allgemeines Krankenhaus-Wien, Innere Medizin III-Nephrologie, Währinger Gürtel 18-20, 1090 Vienna, Austria. rainer.oberbauer@meduniwien.ac.at
authors.forename: Rainer
authors.initials: R
authors.lastname: Oberbauer
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Segoloni
authors.forename: Josep M
authors.initials: JM
authors.lastname: Campistol
authors.forename: Henri
authors.initials: H
authors.lastname: Kreis
authors.forename: Alfredo
authors.initials: A
authors.lastname: Mota
authors.forename: Joseph
authors.initials: J
authors.lastname: Lawen
authors.forename: Graeme
authors.initials: G
authors.lastname: Russ
authors.forename: Josep M
authors.initials: JM
authors.lastname: Grinyó
authors.forename: Giovanni
authors.initials: G
authors.lastname: Stallone
authors.forename: Anders
authors.initials: A
authors.lastname: Hartmann
authors.forename: Jose R
authors.initials: JR
authors.lastname: Pinto
authors.forename: Jeremy
authors.initials: J
authors.lastname: Chapman
authors.forename: James T
authors.initials: JT
authors.lastname: Burke
authors.forename: Yves
authors.initials: Y
authors.lastname: Brault
authors.forename: John F
authors.initials: JF
authors.lastname: Neylan
mesh_terms: D000305:Adrenal Cortex Hormones / Q000627:therapeutic use; D016572:Cyclosporine / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D005500:Follow-Up Studies; D005919:Glomerular Filtration Rate; D006085:Graft Survival / Q000187:drug effects / Q000276:immunology / Q000502:physiology*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D016030:Kidney Transplantation / Q000276:immunology / Q000401:mortality / Q000502:physiology*; D010349:Patient Compliance; D020123:Sirolimus / Q000627:therapeutic use*; D013280:Stomatitis / Q000139:chemically induced / Q000453:epidemiology; D016019:Survival Analysis; D013997:Time Factors
chemical_list: D000305:Adrenal Cortex Hormones; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D020123:Sirolimus