Advantage of rapamycin over mycophenolate mofetil when used with tacrolimus for simultaneous pancreas kidney transplants: Randomized, single-center trial at 10 years

Gaetano Ciancio, J. Sageshima, Linda J Chen, Jeffrey Gaynor, L. Hanson, L. Tueros, E. Montenora Velarde, C. Gomez, Warren Kupin, Giselle Guerra, Adela D Mattiazzi, Alessia Fornoni, Alberto Pugliese, David Roth, M. Wolf, George W Burke

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Abstract

Simultaneous pancreas kidney transplantation (SPKT) is the treatment of choice for patients with type 1 diabetes and end-stage renal disease. Rapamycin and mycophenolate mofetil (MMF) have been used for maintenance immunosuppression with tacrolimus in SPKT; however, long-term outcomes are lacking. From September 2000 through December 2009, 170 SPKT recipients were enrolled in a randomized, prospective trial receiving Rapamycin (n = 84) or MMF (n = 86). All patients received dual induction therapy with thymoglobulin and daclizumab, and low-dose maintenance tacrolimus and corticosteroids. Compared to MMF, rates of freedom from first biopsy-proven acute kidney or pancreas rejection were superior for Rapamycin at year 1 (kidney: 100% vs. 88%; P = 0.001; pancreas: 99% vs. 92%; P = 0.04) and at year 10 (kidney: 88% vs. 71%, P = 0.01; pancreas: 99% vs. 89%, P = 0.01). The higher rates of rejection were associated with withholding MMF (vs. Rapamycin, p = 0.009), generally for gastrointestinal or bone marrow toxicity. There was no significant difference in creatinine, proteinuria, c-peptide, viral infections, lymphoproliferative disorders or posttransplant diabetes. HbA1C and lipid levels were normal in both groups, although higher in the Rapamycin arm. There were no significant differences in patient or allograft survival. In this 10-year SPKT study, Rapamycin in combination with tacrolimus was better tolerated and more effective than MMF. Overall, the patient and allograft survival were equivalent.

Original languageEnglish
Pages (from-to)3363-3376
Number of pages14
JournalAmerican Journal of Transplantation
Volume12
Issue number12
DOIs
StatePublished - Dec 1 2012

Fingerprint

Mycophenolic Acid
Tacrolimus
Sirolimus
Pancreas
Pancreas Transplantation
Transplants
Kidney
Kidney Transplantation
Allografts
Maintenance
Lymphoproliferative Disorders
Virus Diseases
Type 1 Diabetes Mellitus
Proteinuria
Immunosuppression
Chronic Kidney Failure
Creatinine
Adrenal Cortex Hormones
Arm
Bone Marrow

Keywords

  • End-stage renal disease
  • mycophenolate mofetil
  • rapamycin
  • simultaneous kidney-pancreas transplant
  • tacrolimus
  • type 1 diabetes

ASJC Scopus subject areas

  • Transplantation
  • Immunology and Allergy
  • Pharmacology (medical)

Cite this

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title = "Advantage of rapamycin over mycophenolate mofetil when used with tacrolimus for simultaneous pancreas kidney transplants: Randomized, single-center trial at 10 years",
abstract = "Simultaneous pancreas kidney transplantation (SPKT) is the treatment of choice for patients with type 1 diabetes and end-stage renal disease. Rapamycin and mycophenolate mofetil (MMF) have been used for maintenance immunosuppression with tacrolimus in SPKT; however, long-term outcomes are lacking. From September 2000 through December 2009, 170 SPKT recipients were enrolled in a randomized, prospective trial receiving Rapamycin (n = 84) or MMF (n = 86). All patients received dual induction therapy with thymoglobulin and daclizumab, and low-dose maintenance tacrolimus and corticosteroids. Compared to MMF, rates of freedom from first biopsy-proven acute kidney or pancreas rejection were superior for Rapamycin at year 1 (kidney: 100{\%} vs. 88{\%}; P = 0.001; pancreas: 99{\%} vs. 92{\%}; P = 0.04) and at year 10 (kidney: 88{\%} vs. 71{\%}, P = 0.01; pancreas: 99{\%} vs. 89{\%}, P = 0.01). The higher rates of rejection were associated with withholding MMF (vs. Rapamycin, p = 0.009), generally for gastrointestinal or bone marrow toxicity. There was no significant difference in creatinine, proteinuria, c-peptide, viral infections, lymphoproliferative disorders or posttransplant diabetes. HbA1C and lipid levels were normal in both groups, although higher in the Rapamycin arm. There were no significant differences in patient or allograft survival. In this 10-year SPKT study, Rapamycin in combination with tacrolimus was better tolerated and more effective than MMF. Overall, the patient and allograft survival were equivalent.",
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T1 - Advantage of rapamycin over mycophenolate mofetil when used with tacrolimus for simultaneous pancreas kidney transplants

T2 - Randomized, single-center trial at 10 years

AU - Ciancio, Gaetano

AU - Sageshima, J.

AU - Chen, Linda J

AU - Gaynor, Jeffrey

AU - Hanson, L.

AU - Tueros, L.

AU - Velarde, E. Montenora

AU - Gomez, C.

AU - Kupin, Warren

AU - Guerra, Giselle

AU - Mattiazzi, Adela D

AU - Fornoni, Alessia

AU - Pugliese, Alberto

AU - Roth, David

AU - Wolf, M.

AU - Burke, George W

PY - 2012/12/1

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N2 - Simultaneous pancreas kidney transplantation (SPKT) is the treatment of choice for patients with type 1 diabetes and end-stage renal disease. Rapamycin and mycophenolate mofetil (MMF) have been used for maintenance immunosuppression with tacrolimus in SPKT; however, long-term outcomes are lacking. From September 2000 through December 2009, 170 SPKT recipients were enrolled in a randomized, prospective trial receiving Rapamycin (n = 84) or MMF (n = 86). All patients received dual induction therapy with thymoglobulin and daclizumab, and low-dose maintenance tacrolimus and corticosteroids. Compared to MMF, rates of freedom from first biopsy-proven acute kidney or pancreas rejection were superior for Rapamycin at year 1 (kidney: 100% vs. 88%; P = 0.001; pancreas: 99% vs. 92%; P = 0.04) and at year 10 (kidney: 88% vs. 71%, P = 0.01; pancreas: 99% vs. 89%, P = 0.01). The higher rates of rejection were associated with withholding MMF (vs. Rapamycin, p = 0.009), generally for gastrointestinal or bone marrow toxicity. There was no significant difference in creatinine, proteinuria, c-peptide, viral infections, lymphoproliferative disorders or posttransplant diabetes. HbA1C and lipid levels were normal in both groups, although higher in the Rapamycin arm. There were no significant differences in patient or allograft survival. In this 10-year SPKT study, Rapamycin in combination with tacrolimus was better tolerated and more effective than MMF. Overall, the patient and allograft survival were equivalent.

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