A randomized long-term trial of tacrolimus/sirolimus versus tacrolimums/mycophenolate versus cyclosporine/sirolimus in renal transplantation: three-year analysis.
BACKGROUND
We report three-year (interim) effects of combining sirolimus (Siro) vs. mycophenolate mofetil (MMF) as adjunctive therapy with calcineurin inhibitors (CI) in renal transplantation in the three different CI-based regimens.


METHODS
Between May 2000 and December 2001, 150 recipients of deceased donor (DD) and living donor (LD) kidney transplants were randomized into three groups (n=50/group): Group A (Tacro/Siro), Group B (Tacro/MMF) and Group C (CsA/Siro). This report details drug dosing and monitoring, protocol discontinuance, biopsy-proven rejection, graft failure, other adverse events, and death at 36 months postoperatively.


RESULTS
Actual patient and graft survival respectively in Group A was 90% and 82%, in Group B was 92% and 88%, and in Group C was 96% and 88% (not significant). Biopsy-confirmed acute rejection incidents showed a trend in favor of Group B (10%) vs. Group A (26%) and Group C (20%) combined (P=0.07). The geometric mean */SE serum creatinine concentration and arithmetic mean +/- SE Cockroft-Gault creatinine clearance calculations, respectively, were 1.39*/1.1 and 72.8+/-4.3 for Group A, 1.36*/1.1 and 72.1+/-4.1 for Group B, and 1.60*/1.1 and 61.8+/-3.8 for Group C, a statistically favorable difference for Group B over Group C (P=0.04). There was also less de novo development of posttransplant diabetes mellitus and lipid disorders in Group B vs. A and C (P<0.04).


CONCLUSIONS
This three-year (interim) analysis has indicated a trend towards better graft function, fewer endocrine disorders, and fewer acute rejection episodes comparing adjunctive MMF and Tacro vs. Siro and Tacro or Siro and CsA, in the dosages used.
The Lillian Jean Kaplan Renal Transplant Center, Department of Surgery, Division of Transplantation, University of Miami Miller School of Medicine, PO Box 012440, Miami, FL 33101, USA. gciancio@med.miami.edu
Gaetano
G
Ciancio
George W
GW
Burke
Jeffrey J
JJ
Gaynor
Phillip
P
Ruiz
David
D
Roth
Warren
W
Kupin
Anne
A
Rosen
Joshua
J
Miller
D000293:Adolescent; D000328:Adult; D000368:Aged; D001794:Blood Pressure; D018592:Cross-Over Studies; D003920:Diabetes Mellitus / Q000209:etiology; D050171:Dyslipidemias / Q000209:etiology; D005260:Female; D006084:Graft Rejection / Q000453:epidemiology; D006085:Graft Survival; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D015994:Incidence; D007668:Kidney / Q000503:physiopathology; D016030:Kidney Transplantation / Q000009:adverse effects / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood; D020123:Sirolimus / Q000008:administration & dosage* / Q000097:blood; D016559:Tacrolimus / Q000008:administration & dosage* / Q000097:blood
D007166:Immunosuppressive Agents; D009173:Mycophenolic Acid; D020123:Sirolimus; D016559:Tacrolimus