Multicenter, randomized study of the use of everolimus with tacrolimus after renal transplantation demonstrates its effectiveness.
BACKGROUND
Clinical data are lacking concerning concomitant administration of everolimus and tacrolimus in renal transplant recipients.


METHODS
In a prospective, multicenter, open-label, exploratory, randomized, 6-month study, 92 de novo renal transplant patients received everolimus, steroids, and basiliximab with low or standard tacrolimus exposure. The primary objective was to compare renal function at 6 months after transplant.


RESULTS
Mean 6-month serum creatinine (primary safety variable) was 112+/-31 micromol/L (1.26+/-0.35 mg/dL) and 127+/-50 micromol/L (1.44+/-0.57 mg/dL) in the low and standard tacrolimus groups, respectively, (n.s.); mean estimated GFR (Nankivell) was 75.3+/-16.6 mL/min and 72.5+/-15.2 mL/min (n.s.). Biopsy-proven acute rejection occurred in 13 patients: seven (14%) in the low tacrolimus group and six (14%) in the standard tacrolimus group, n.s. One graft was lost in the standard tacrolimus group. No patients died.


CONCLUSIONS
Tacrolimus exposure reduction in the presence of everolimus, steroids and basiliximab induction results in good efficacy in de novo renal transplant recipients with very well-preserved renal function. Additional studies are warranted because between-group comparisons were limited by the relatively small differences in tacrolimus exposure in the 2 arms; trough levels were toward the upper end of the low-exposure ranges and toward the bottom of the standard-exposure ranges.
Chan
Laurence
L
Health Sciences Center, University of Colorado, Denver, CO 80262, USA. larry.chan@uchsc.edu
Greenstein
Stuart
S
Hardy
Mark A
MA
Hartmann
Erica
E
Bunnapradist
Suphamai
S
Cibrik
Diane
D
Shaw
Leslie M
LM
Munir
Laura
L
Ulbricht
Bettina
B
Cooper
Matthew
M
D000328:Adult; D004359:Drug Therapy, Combination; D000068338:Everolimus; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007676:Kidney Failure, Chronic / Q000209:etiology / Q000601:surgery*; D016030:Kidney Transplantation / Q000276:immunology*; D019520:Living Donors / Q000706:statistics & numerical data; D008297:Male; D008875:Middle Aged; D020123:Sirolimus / Q000031:analogs & derivatives* / Q000627:therapeutic use; D016559:Tacrolimus / Q000627:therapeutic use*; D014019:Tissue Donors / Q000706:statistics & numerical data
D007166:Immunosuppressive Agents; D000068338:Everolimus; D020123:Sirolimus; D016559:Tacrolimus