Efficacy on renal function of early conversion from cyclosporine to sirolimus 3 months after renal transplantation: concept study.
Sirolimus (SRL) allows to minimize the use of cyclosporine (CsA), but de novo administration after transplantation is associated with various complications. We report a prospective, open-label, multicenter randomized study to evaluate conversion from a CsA-based regimen to a SRL-based regimen 3 months after transplantation. One hundred ninety-two of a total of 237 patients were eligible at 3 months to be converted to SRL (n = 95) or to continue CsA (n = 97). All patients were also given mycophenolate mofetil (MMF) and oral steroids, planned to be discontinued at month 8. The primary endpoint, the clearance estimated according to Cockcroft and Gault at week 52, was significantly better in the SRL group (68.9 vs. 64.4 mL/min, p = 0.017). Patient and graft survival were not statistically different. The incidence of acute rejection episodes, mainly occurring after withdrawal of steroids, was numerically but not statistically higher in the SRL group (17% vs. 8%, p = 0.071). Sixteen patients discontinued SRL, mainly for adverse events (n = 11), and seven patients discontinued CsA for renal failure or acute rejection. Significantly, more patients in the SRL group reported aphthous, diarrhea, acne and high triglyceride levels. Conversion CsA to SRL 3 months after transplantation combined with MMF is associated with improvement in renal function.
Service Nephrologie Immunologie Clinique, CHRU Tours, EA 4245, University François Rabelais, Tours, France. lebranchu@med.univ-tour.fr
Y
Y
Lebranchu
A
A
Thierry
O
O
Toupance
P F
PF
Westeel
I
I
Etienne
E
E
Thervet
B
B
Moulin
T
T
Frouget
Y
Y
Le Meur
D
D
Glotz
A-E
AE
Heng
C
C
Onno
M
M
Buchler
S
S
Girardot-Seguin
B
B
Hurault de Ligny
D000305:Adrenal Cortex Hormones / Q000627:therapeutic use; D000328:Adult; D000368:Aged; D016572:Cyclosporine / Q000009:adverse effects / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D005602:France; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use; D007677:Kidney Function Tests; D016030:Kidney Transplantation / Q000276:immunology / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000031:analogs & derivatives / Q000627:therapeutic use; D018579:Patient Selection; D011446:Prospective Studies; D020123:Sirolimus / Q000627:therapeutic use*; D013997:Time Factors; D014019:Tissue Donors / Q000706:statistics & numerical data; D055815:Young Adult
D000305:Adrenal Cortex Hormones; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D009173:Mycophenolic Acid; D020123:Sirolimus