Early cyclosporine withdrawal from a sirolimus-based regimen results in better renal allograft survival and renal function at 48 months after transplantation.
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transplantation were randomly assigned at 3 months to remain on triple therapy (SRL-CsA-ST, n = 215) or to have CsA withdrawn and SRL trough concentrations increased (SRL-ST, n = 215).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.
Oberbauer
Rainer
R
Allgemeines Krankenhaus-Wien, Innere Medizin III-Nephrologie, Währinger Gürtel 18-20, 1090 Vienna, Austria. rainer.oberbauer@meduniwien.ac.at
Segoloni
Giuseppe
G
Campistol
Josep M
JM
Kreis
Henri
H
Mota
Alfredo
A
Lawen
Joseph
J
Russ
Graeme
G
Grinyó
Josep M
JM
Stallone
Giovanni
G
Hartmann
Anders
A
Pinto
Jose R
JR
Chapman
Jeremy
J
Burke
James T
JT
Brault
Yves
Y
Neylan
John F
JF
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
D000305:Adrenal Cortex Hormones; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D020123:Sirolimus