A randomized long-term trial of tacrolimus/sirolimus versus tacrolimums/mycophenolate versus cyclosporine/sirolimus in renal transplantation: Three-year analysis

Research output: Contribution to journalArticle

87 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)845-852
Number of pages8
JournalTransplantation
Volume81
Issue number6
DOIs
StatePublished - Mar 1 2006

Fingerprint

Tacrolimus
Sirolimus
Kidney Transplantation
Cyclosporine
Mycophenolic Acid
Creatinine
Transplants
Biopsy
Drug Monitoring
Living Donors
Graft Rejection
Graft Survival
Diabetes Mellitus
Tissue Donors
Kidney
Lipids
Serum
Calcineurin Inhibitors

Keywords

  • Acute rejection
  • Cyclosporine
  • Mycophenolate mofetil
  • Renal allograft
  • Sirolimus
  • Tacrolimus

ASJC Scopus subject areas

  • Transplantation
  • Immunology

Cite this

@article{49d5bbba89564133b7e8cccf45456eb7,
title = "A randomized long-term trial of tacrolimus/sirolimus versus tacrolimums/mycophenolate versus cyclosporine/sirolimus in renal transplantation: Three-year analysis",
abstract = "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.",
keywords = "Acute rejection, Cyclosporine, Mycophenolate mofetil, Renal allograft, Sirolimus, Tacrolimus",
author = "Gaetano Ciancio and Burke, {George W} and Jeffrey Gaynor and Phillip Ruiz and David Roth and Warren Kupin and Anne Rosen and Joshua Miller",
year = "2006",
month = "3",
day = "1",
doi = "10.1097/01.tp.0000203894.53714.27",
language = "English",
volume = "81",
pages = "845--852",
journal = "Transplantation",
issn = "0041-1337",
publisher = "Lippincott Williams and Wilkins",
number = "6",

}

TY - JOUR

T1 - A randomized long-term trial of tacrolimus/sirolimus versus tacrolimums/mycophenolate versus cyclosporine/sirolimus in renal transplantation

T2 - Three-year analysis

AU - Ciancio, Gaetano

AU - Burke, George W

AU - Gaynor, Jeffrey

AU - Ruiz, Phillip

AU - Roth, David

AU - Kupin, Warren

AU - Rosen, Anne

AU - Miller, Joshua

PY - 2006/3/1

Y1 - 2006/3/1

N2 - 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.

AB - 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.

KW - Acute rejection

KW - Cyclosporine

KW - Mycophenolate mofetil

KW - Renal allograft

KW - Sirolimus

KW - Tacrolimus

UR - http://www.scopus.com/inward/record.url?scp=33645649901&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33645649901&partnerID=8YFLogxK

U2 - 10.1097/01.tp.0000203894.53714.27

DO - 10.1097/01.tp.0000203894.53714.27

M3 - Article

C2 - 16570006

AN - SCOPUS:33645649901

VL - 81

SP - 845

EP - 852

JO - Transplantation

JF - Transplantation

SN - 0041-1337

IS - 6

ER -