Prospective, randomized trial of the effect of antibody induction in simultaneous pancreas and kidney transplantation: Three-year results

George W. Burke, Dixon B. Kaufman, J. Michael Millis, A. Osama Gaber, Christopher P. Johnson, David E R Sutherland, Jeffrey D. Punch, Barry D. Kahan, Eugene Schweitzer, Alan Norman Langnas, James Perkins, John Scandling, Waldo Concepcion, Mark D. Stegall, James A. Schulak, Paul F. Gores, Enrico Benedetti, Gabriel Danovitch, Alice K. Henning, Marilyn R. BartucciSarah Smith, William E. Fitzsimmons

Research output: Contribution to journalArticle

66 Citations (Scopus)

Abstract

Background. Historically, antibody induction has been used because of the higher immunologic risk of graft loss or rejection observed in simultaneous pancreas and kidney (SPK) transplantation compared with kidney transplantation alone. This trial was designed to assess the effect of antibody induction in SPK transplant recipients receiving tacrolimus, mycophenolate mofetil, and corticosteroids. Induction agents included T-cell-depleting and interleukin-2 receptor antibodies. Methods. A total of 174 SPK transplant recipients were enrolled in a prospective, open-label, multicenter study. They were randomized to induction (n=87) or non-induction (n=87) groups and followed for 3 years. Results. At 3 years, actual patient (94.3% and 89.7%) and pancreas (75.9% and 75.9%) survivals were similar between the induction and non-induction groups, respectively. Actual kidney survival was similar at 1 and 2 years, but at 3 years, it was significantly better in the induction group compared with the non-induction group (92% vs. 81.6%; P=0.04). At 3 years, median serum creatinine and hemoglobin AIC were similar between the induction and non-induction groups (1.35 mg/dL and 1.20 mg/dL, 5.4% and 5.5%, respectively). Three-year cumulative incidence of biopsy-confirmed, treated acute kidney rejection in the induction and non-induction groups was 19.5% and 27.5% (P=0.14), respectively, with odds 4.6 times greater in African Americans regardless of treatment (P=0.004). Significantly higher rates of cytomegalovirus (CMV) viremia and CMV syndrome occurred in those receiving T-cell-depleting antibody induction (36.1%) when compared with those receiving anti-interleukin-2 receptor antibodies (2%) and non-induction (8.1%) (P<0.0001). Conclusions. Tacrolimus, mycophenolate mofetil, and corticosteroids resulted in excellent safety and efficacy in SPK transplant recipients. Actual 3-year kidney survival was significantly better in the induction group; however, CMV viremia and CMV syndrome rates were significantly higher in the T-cell-depleting antibody group. African Americans demonstrated a significantly greater risk of acute rejection despite antibody induction. Decisions regarding the use of induction therapy must weigh the risk of kidney graft loss or rejection against the risk of infection.

Original languageEnglish (US)
Pages (from-to)1269-1275
Number of pages7
JournalTransplantation
Volume77
Issue number8
DOIs
StatePublished - Apr 27 2004

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Pancreas Transplantation
Kidney Transplantation
Kidney
Antibodies
Cytomegalovirus
Pancreas
Mycophenolic Acid
Interleukin-2 Receptors
Viremia
Tacrolimus
T-Lymphocytes
African Americans
Adrenal Cortex Hormones
Transplants
Multicenter Studies
Creatinine
Hemoglobins
Biopsy
Safety
Survival

ASJC Scopus subject areas

  • Transplantation

Cite this

Burke, G. W., Kaufman, D. B., Millis, J. M., Gaber, A. O., Johnson, C. P., Sutherland, D. E. R., ... Fitzsimmons, W. E. (2004). Prospective, randomized trial of the effect of antibody induction in simultaneous pancreas and kidney transplantation: Three-year results. Transplantation, 77(8), 1269-1275. https://doi.org/10.1097/01.TP.0000123903.12311.36

Prospective, randomized trial of the effect of antibody induction in simultaneous pancreas and kidney transplantation : Three-year results. / Burke, George W.; Kaufman, Dixon B.; Millis, J. Michael; Gaber, A. Osama; Johnson, Christopher P.; Sutherland, David E R; Punch, Jeffrey D.; Kahan, Barry D.; Schweitzer, Eugene; Langnas, Alan Norman; Perkins, James; Scandling, John; Concepcion, Waldo; Stegall, Mark D.; Schulak, James A.; Gores, Paul F.; Benedetti, Enrico; Danovitch, Gabriel; Henning, Alice K.; Bartucci, Marilyn R.; Smith, Sarah; Fitzsimmons, William E.

In: Transplantation, Vol. 77, No. 8, 27.04.2004, p. 1269-1275.

Research output: Contribution to journalArticle

Burke, GW, Kaufman, DB, Millis, JM, Gaber, AO, Johnson, CP, Sutherland, DER, Punch, JD, Kahan, BD, Schweitzer, E, Langnas, AN, Perkins, J, Scandling, J, Concepcion, W, Stegall, MD, Schulak, JA, Gores, PF, Benedetti, E, Danovitch, G, Henning, AK, Bartucci, MR, Smith, S & Fitzsimmons, WE 2004, 'Prospective, randomized trial of the effect of antibody induction in simultaneous pancreas and kidney transplantation: Three-year results', Transplantation, vol. 77, no. 8, pp. 1269-1275. https://doi.org/10.1097/01.TP.0000123903.12311.36
Burke, George W. ; Kaufman, Dixon B. ; Millis, J. Michael ; Gaber, A. Osama ; Johnson, Christopher P. ; Sutherland, David E R ; Punch, Jeffrey D. ; Kahan, Barry D. ; Schweitzer, Eugene ; Langnas, Alan Norman ; Perkins, James ; Scandling, John ; Concepcion, Waldo ; Stegall, Mark D. ; Schulak, James A. ; Gores, Paul F. ; Benedetti, Enrico ; Danovitch, Gabriel ; Henning, Alice K. ; Bartucci, Marilyn R. ; Smith, Sarah ; Fitzsimmons, William E. / Prospective, randomized trial of the effect of antibody induction in simultaneous pancreas and kidney transplantation : Three-year results. In: Transplantation. 2004 ; Vol. 77, No. 8. pp. 1269-1275.
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abstract = "Background. Historically, antibody induction has been used because of the higher immunologic risk of graft loss or rejection observed in simultaneous pancreas and kidney (SPK) transplantation compared with kidney transplantation alone. This trial was designed to assess the effect of antibody induction in SPK transplant recipients receiving tacrolimus, mycophenolate mofetil, and corticosteroids. Induction agents included T-cell-depleting and interleukin-2 receptor antibodies. Methods. A total of 174 SPK transplant recipients were enrolled in a prospective, open-label, multicenter study. They were randomized to induction (n=87) or non-induction (n=87) groups and followed for 3 years. Results. At 3 years, actual patient (94.3{\%} and 89.7{\%}) and pancreas (75.9{\%} and 75.9{\%}) survivals were similar between the induction and non-induction groups, respectively. Actual kidney survival was similar at 1 and 2 years, but at 3 years, it was significantly better in the induction group compared with the non-induction group (92{\%} vs. 81.6{\%}; P=0.04). At 3 years, median serum creatinine and hemoglobin AIC were similar between the induction and non-induction groups (1.35 mg/dL and 1.20 mg/dL, 5.4{\%} and 5.5{\%}, respectively). Three-year cumulative incidence of biopsy-confirmed, treated acute kidney rejection in the induction and non-induction groups was 19.5{\%} and 27.5{\%} (P=0.14), respectively, with odds 4.6 times greater in African Americans regardless of treatment (P=0.004). Significantly higher rates of cytomegalovirus (CMV) viremia and CMV syndrome occurred in those receiving T-cell-depleting antibody induction (36.1{\%}) when compared with those receiving anti-interleukin-2 receptor antibodies (2{\%}) and non-induction (8.1{\%}) (P<0.0001). Conclusions. Tacrolimus, mycophenolate mofetil, and corticosteroids resulted in excellent safety and efficacy in SPK transplant recipients. Actual 3-year kidney survival was significantly better in the induction group; however, CMV viremia and CMV syndrome rates were significantly higher in the T-cell-depleting antibody group. African Americans demonstrated a significantly greater risk of acute rejection despite antibody induction. Decisions regarding the use of induction therapy must weigh the risk of kidney graft loss or rejection against the risk of infection.",
author = "Burke, {George W.} and Kaufman, {Dixon B.} and Millis, {J. Michael} and Gaber, {A. Osama} and Johnson, {Christopher P.} and Sutherland, {David E R} and Punch, {Jeffrey D.} and Kahan, {Barry D.} and Eugene Schweitzer and Langnas, {Alan Norman} and James Perkins and John Scandling and Waldo Concepcion and Stegall, {Mark D.} and Schulak, {James A.} and Gores, {Paul F.} and Enrico Benedetti and Gabriel Danovitch and Henning, {Alice K.} and Bartucci, {Marilyn R.} and Sarah Smith and Fitzsimmons, {William E.}",
year = "2004",
month = "4",
day = "27",
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language = "English (US)",
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TY - JOUR

T1 - Prospective, randomized trial of the effect of antibody induction in simultaneous pancreas and kidney transplantation

T2 - Three-year results

AU - Burke, George W.

AU - Kaufman, Dixon B.

AU - Millis, J. Michael

AU - Gaber, A. Osama

AU - Johnson, Christopher P.

AU - Sutherland, David E R

AU - Punch, Jeffrey D.

AU - Kahan, Barry D.

AU - Schweitzer, Eugene

AU - Langnas, Alan Norman

AU - Perkins, James

AU - Scandling, John

AU - Concepcion, Waldo

AU - Stegall, Mark D.

AU - Schulak, James A.

AU - Gores, Paul F.

AU - Benedetti, Enrico

AU - Danovitch, Gabriel

AU - Henning, Alice K.

AU - Bartucci, Marilyn R.

AU - Smith, Sarah

AU - Fitzsimmons, William E.

PY - 2004/4/27

Y1 - 2004/4/27

N2 - Background. Historically, antibody induction has been used because of the higher immunologic risk of graft loss or rejection observed in simultaneous pancreas and kidney (SPK) transplantation compared with kidney transplantation alone. This trial was designed to assess the effect of antibody induction in SPK transplant recipients receiving tacrolimus, mycophenolate mofetil, and corticosteroids. Induction agents included T-cell-depleting and interleukin-2 receptor antibodies. Methods. A total of 174 SPK transplant recipients were enrolled in a prospective, open-label, multicenter study. They were randomized to induction (n=87) or non-induction (n=87) groups and followed for 3 years. Results. At 3 years, actual patient (94.3% and 89.7%) and pancreas (75.9% and 75.9%) survivals were similar between the induction and non-induction groups, respectively. Actual kidney survival was similar at 1 and 2 years, but at 3 years, it was significantly better in the induction group compared with the non-induction group (92% vs. 81.6%; P=0.04). At 3 years, median serum creatinine and hemoglobin AIC were similar between the induction and non-induction groups (1.35 mg/dL and 1.20 mg/dL, 5.4% and 5.5%, respectively). Three-year cumulative incidence of biopsy-confirmed, treated acute kidney rejection in the induction and non-induction groups was 19.5% and 27.5% (P=0.14), respectively, with odds 4.6 times greater in African Americans regardless of treatment (P=0.004). Significantly higher rates of cytomegalovirus (CMV) viremia and CMV syndrome occurred in those receiving T-cell-depleting antibody induction (36.1%) when compared with those receiving anti-interleukin-2 receptor antibodies (2%) and non-induction (8.1%) (P<0.0001). Conclusions. Tacrolimus, mycophenolate mofetil, and corticosteroids resulted in excellent safety and efficacy in SPK transplant recipients. Actual 3-year kidney survival was significantly better in the induction group; however, CMV viremia and CMV syndrome rates were significantly higher in the T-cell-depleting antibody group. African Americans demonstrated a significantly greater risk of acute rejection despite antibody induction. Decisions regarding the use of induction therapy must weigh the risk of kidney graft loss or rejection against the risk of infection.

AB - Background. Historically, antibody induction has been used because of the higher immunologic risk of graft loss or rejection observed in simultaneous pancreas and kidney (SPK) transplantation compared with kidney transplantation alone. This trial was designed to assess the effect of antibody induction in SPK transplant recipients receiving tacrolimus, mycophenolate mofetil, and corticosteroids. Induction agents included T-cell-depleting and interleukin-2 receptor antibodies. Methods. A total of 174 SPK transplant recipients were enrolled in a prospective, open-label, multicenter study. They were randomized to induction (n=87) or non-induction (n=87) groups and followed for 3 years. Results. At 3 years, actual patient (94.3% and 89.7%) and pancreas (75.9% and 75.9%) survivals were similar between the induction and non-induction groups, respectively. Actual kidney survival was similar at 1 and 2 years, but at 3 years, it was significantly better in the induction group compared with the non-induction group (92% vs. 81.6%; P=0.04). At 3 years, median serum creatinine and hemoglobin AIC were similar between the induction and non-induction groups (1.35 mg/dL and 1.20 mg/dL, 5.4% and 5.5%, respectively). Three-year cumulative incidence of biopsy-confirmed, treated acute kidney rejection in the induction and non-induction groups was 19.5% and 27.5% (P=0.14), respectively, with odds 4.6 times greater in African Americans regardless of treatment (P=0.004). Significantly higher rates of cytomegalovirus (CMV) viremia and CMV syndrome occurred in those receiving T-cell-depleting antibody induction (36.1%) when compared with those receiving anti-interleukin-2 receptor antibodies (2%) and non-induction (8.1%) (P<0.0001). Conclusions. Tacrolimus, mycophenolate mofetil, and corticosteroids resulted in excellent safety and efficacy in SPK transplant recipients. Actual 3-year kidney survival was significantly better in the induction group; however, CMV viremia and CMV syndrome rates were significantly higher in the T-cell-depleting antibody group. African Americans demonstrated a significantly greater risk of acute rejection despite antibody induction. Decisions regarding the use of induction therapy must weigh the risk of kidney graft loss or rejection against the risk of infection.

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