Mycophenolate mofetil decreases rejection in simultaneous pancreas- kidney transplantation when combined with tacrolimus or cyclosporine

Mark D Stegall, Marta Simon, Michael E. Wachs, Lawrence Chan, Charles Nolan, Igal Kam

Research output: Contribution to journalArticle

77 Citations (Scopus)

Abstract

Background. Historically, the acute rejection rates in simultaneous pancreas-kidney (SPK) recipients have been extremely high (50-80%), with many second and third rejection episodes despite the use of quadruple immunosuppression (antibody induction and cyclosporine [CsA]-azathioprine [AZA]-based maintenance immunosuppression). Although this acute rejection has rarely led to graft loss, it has been a great cause of morbidity and of significantly increased cost. In an attempt to decrease the acute rejection rate and related morbidity in SPK transplant recipients, we compared two 'state-of-the-art' immunosuppression regimens in a prospective, randomized, single-center study. Methods. Patients who received SPK transplants were randomized to receive either tacrolimus (TAC) and mycophenolate mofetil (MMF, n=18) or CsA (Neworal formulation) and MMF (n=18). All patients received OKT3 induction and prednisone, which was tapered to 5mg/day by 6 months after transplantation. All rejection episodes were biopsy proven. In addition, metabolic control (HgB(A1C), hypertension, serum cholesterol), drug toxicity, and infection also were measured. Data were compared with that of a historical group (n=18) who received conventional CsA (Sand-immune formulation) and AZA-based immunosuppression. Results. The incidence of biopsy-proven acute rejection was 11% in the both the TAC-MMF and CsA-MMF groups with only two patients in each group experiencing a rejection episode. This rejection rate was significantly decreased from that of the CsA-AZA historical group (77%, P<0.01). There were no significant differences in infection rates, including cytomegalovirus, or in metabolic control (Hgb(A1C), hypertension, and cholesterol levels). All patients remained on their initial immunosuppression regimen for the first 3 months after transplantation. Between 3 and 6 months after transplantation, three patients were switched from TAC and CsA for recurrent migraine headaches, posttransplant diabetes, and chronic cytomegalovirus infection. Two patient in the CsA-MMF group died of nonimmunologic causes (aspiration pneumonia and arrhythmia) between 3 and 6 months after transplantation. Conclusions. The data from this study show that MMF treatment significantly decreases the incidence of biopsy-proven acute rejection in SPK transplant recipients compared with AZA-treated historical controls. In addition, we conclude that TAC and CsA (Neoral), when combined with MMF, yield similar, low acute rejection rates with similar graft function and metabolic control.

Original languageEnglish (US)
Pages (from-to)1695-1700
Number of pages6
JournalTransplantation
Volume64
Issue number12
DOIs
StatePublished - Dec 27 1997
Externally publishedYes

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Mycophenolic Acid
Pancreas Transplantation
Tacrolimus
Kidney Transplantation
Cyclosporine
Immunosuppression
Azathioprine
Pancreas
Transplantation
Kidney
Transplants
Biopsy
Cholesterol
Hypertension
Morbidity
Muromonab-CD3
Aspiration Pneumonia
Incidence
Cytomegalovirus Infections
Prednisone

ASJC Scopus subject areas

  • Transplantation
  • Immunology

Cite this

Mycophenolate mofetil decreases rejection in simultaneous pancreas- kidney transplantation when combined with tacrolimus or cyclosporine. / Stegall, Mark D; Simon, Marta; Wachs, Michael E.; Chan, Lawrence; Nolan, Charles; Kam, Igal.

In: Transplantation, Vol. 64, No. 12, 27.12.1997, p. 1695-1700.

Research output: Contribution to journalArticle

Stegall, Mark D ; Simon, Marta ; Wachs, Michael E. ; Chan, Lawrence ; Nolan, Charles ; Kam, Igal. / Mycophenolate mofetil decreases rejection in simultaneous pancreas- kidney transplantation when combined with tacrolimus or cyclosporine. In: Transplantation. 1997 ; Vol. 64, No. 12. pp. 1695-1700.
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title = "Mycophenolate mofetil decreases rejection in simultaneous pancreas- kidney transplantation when combined with tacrolimus or cyclosporine",
abstract = "Background. Historically, the acute rejection rates in simultaneous pancreas-kidney (SPK) recipients have been extremely high (50-80{\%}), with many second and third rejection episodes despite the use of quadruple immunosuppression (antibody induction and cyclosporine [CsA]-azathioprine [AZA]-based maintenance immunosuppression). Although this acute rejection has rarely led to graft loss, it has been a great cause of morbidity and of significantly increased cost. In an attempt to decrease the acute rejection rate and related morbidity in SPK transplant recipients, we compared two 'state-of-the-art' immunosuppression regimens in a prospective, randomized, single-center study. Methods. Patients who received SPK transplants were randomized to receive either tacrolimus (TAC) and mycophenolate mofetil (MMF, n=18) or CsA (Neworal formulation) and MMF (n=18). All patients received OKT3 induction and prednisone, which was tapered to 5mg/day by 6 months after transplantation. All rejection episodes were biopsy proven. In addition, metabolic control (HgB(A1C), hypertension, serum cholesterol), drug toxicity, and infection also were measured. Data were compared with that of a historical group (n=18) who received conventional CsA (Sand-immune formulation) and AZA-based immunosuppression. Results. The incidence of biopsy-proven acute rejection was 11{\%} in the both the TAC-MMF and CsA-MMF groups with only two patients in each group experiencing a rejection episode. This rejection rate was significantly decreased from that of the CsA-AZA historical group (77{\%}, P<0.01). There were no significant differences in infection rates, including cytomegalovirus, or in metabolic control (Hgb(A1C), hypertension, and cholesterol levels). All patients remained on their initial immunosuppression regimen for the first 3 months after transplantation. Between 3 and 6 months after transplantation, three patients were switched from TAC and CsA for recurrent migraine headaches, posttransplant diabetes, and chronic cytomegalovirus infection. Two patient in the CsA-MMF group died of nonimmunologic causes (aspiration pneumonia and arrhythmia) between 3 and 6 months after transplantation. Conclusions. The data from this study show that MMF treatment significantly decreases the incidence of biopsy-proven acute rejection in SPK transplant recipients compared with AZA-treated historical controls. In addition, we conclude that TAC and CsA (Neoral), when combined with MMF, yield similar, low acute rejection rates with similar graft function and metabolic control.",
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AU - Stegall, Mark D

AU - Simon, Marta

AU - Wachs, Michael E.

AU - Chan, Lawrence

AU - Nolan, Charles

AU - Kam, Igal

PY - 1997/12/27

Y1 - 1997/12/27

N2 - Background. Historically, the acute rejection rates in simultaneous pancreas-kidney (SPK) recipients have been extremely high (50-80%), with many second and third rejection episodes despite the use of quadruple immunosuppression (antibody induction and cyclosporine [CsA]-azathioprine [AZA]-based maintenance immunosuppression). Although this acute rejection has rarely led to graft loss, it has been a great cause of morbidity and of significantly increased cost. In an attempt to decrease the acute rejection rate and related morbidity in SPK transplant recipients, we compared two 'state-of-the-art' immunosuppression regimens in a prospective, randomized, single-center study. Methods. Patients who received SPK transplants were randomized to receive either tacrolimus (TAC) and mycophenolate mofetil (MMF, n=18) or CsA (Neworal formulation) and MMF (n=18). All patients received OKT3 induction and prednisone, which was tapered to 5mg/day by 6 months after transplantation. All rejection episodes were biopsy proven. In addition, metabolic control (HgB(A1C), hypertension, serum cholesterol), drug toxicity, and infection also were measured. Data were compared with that of a historical group (n=18) who received conventional CsA (Sand-immune formulation) and AZA-based immunosuppression. Results. The incidence of biopsy-proven acute rejection was 11% in the both the TAC-MMF and CsA-MMF groups with only two patients in each group experiencing a rejection episode. This rejection rate was significantly decreased from that of the CsA-AZA historical group (77%, P<0.01). There were no significant differences in infection rates, including cytomegalovirus, or in metabolic control (Hgb(A1C), hypertension, and cholesterol levels). All patients remained on their initial immunosuppression regimen for the first 3 months after transplantation. Between 3 and 6 months after transplantation, three patients were switched from TAC and CsA for recurrent migraine headaches, posttransplant diabetes, and chronic cytomegalovirus infection. Two patient in the CsA-MMF group died of nonimmunologic causes (aspiration pneumonia and arrhythmia) between 3 and 6 months after transplantation. Conclusions. The data from this study show that MMF treatment significantly decreases the incidence of biopsy-proven acute rejection in SPK transplant recipients compared with AZA-treated historical controls. In addition, we conclude that TAC and CsA (Neoral), when combined with MMF, yield similar, low acute rejection rates with similar graft function and metabolic control.

AB - Background. Historically, the acute rejection rates in simultaneous pancreas-kidney (SPK) recipients have been extremely high (50-80%), with many second and third rejection episodes despite the use of quadruple immunosuppression (antibody induction and cyclosporine [CsA]-azathioprine [AZA]-based maintenance immunosuppression). Although this acute rejection has rarely led to graft loss, it has been a great cause of morbidity and of significantly increased cost. In an attempt to decrease the acute rejection rate and related morbidity in SPK transplant recipients, we compared two 'state-of-the-art' immunosuppression regimens in a prospective, randomized, single-center study. Methods. Patients who received SPK transplants were randomized to receive either tacrolimus (TAC) and mycophenolate mofetil (MMF, n=18) or CsA (Neworal formulation) and MMF (n=18). All patients received OKT3 induction and prednisone, which was tapered to 5mg/day by 6 months after transplantation. All rejection episodes were biopsy proven. In addition, metabolic control (HgB(A1C), hypertension, serum cholesterol), drug toxicity, and infection also were measured. Data were compared with that of a historical group (n=18) who received conventional CsA (Sand-immune formulation) and AZA-based immunosuppression. Results. The incidence of biopsy-proven acute rejection was 11% in the both the TAC-MMF and CsA-MMF groups with only two patients in each group experiencing a rejection episode. This rejection rate was significantly decreased from that of the CsA-AZA historical group (77%, P<0.01). There were no significant differences in infection rates, including cytomegalovirus, or in metabolic control (Hgb(A1C), hypertension, and cholesterol levels). All patients remained on their initial immunosuppression regimen for the first 3 months after transplantation. Between 3 and 6 months after transplantation, three patients were switched from TAC and CsA for recurrent migraine headaches, posttransplant diabetes, and chronic cytomegalovirus infection. Two patient in the CsA-MMF group died of nonimmunologic causes (aspiration pneumonia and arrhythmia) between 3 and 6 months after transplantation. Conclusions. The data from this study show that MMF treatment significantly decreases the incidence of biopsy-proven acute rejection in SPK transplant recipients compared with AZA-treated historical controls. In addition, we conclude that TAC and CsA (Neoral), when combined with MMF, yield similar, low acute rejection rates with similar graft function and metabolic control.

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