Prospective, randomized trial of the effect of antibody induction in simultaneous pancreas and kidney transplantation: three-year results.
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, multi-center 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 A1C 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.
Burke
George W
GW
Department of Surgery, University of Miami, Miami, Florida 33136, USA. GBurke@med.miami.edu
Kaufman
Dixon B
DB
Millis
J Michael
JM
Gaber
A Osama
AO
Johnson
Christopher P
CP
Sutherland
David E R
DE
Punch
Jeffrey D
JD
Kahan
Barry D
BD
Schweitzer
Eugene
E
Langnas
Alan
A
Perkins
James
J
Scandling
John
J
Concepcion
Waldo
W
Stegall
Mark D
MD
Schulak
James A
JA
Gores
Paul F
PF
Benedetti
Enrico
E
Danovitch
Gabriel
G
Henning
Alice K
AK
Bartucci
Marilyn R
MR
Smith
Sarah
S
Fitzsimmons
William E
WE
D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D000961:Antilymphocyte Serum / Q000627:therapeutic use; D005260:Female; D006085:Graft Survival / Q000187:drug effects / Q000276:immunology; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D016030:Kidney Transplantation / Q000276:immunology*; D008212:Lymphocyte Depletion; D008297:Male; D016035:Pancreas Transplantation / Q000276:immunology*; D011446:Prospective Studies; D015375:Receptors, Interleukin-2 / Q000276:immunology; D013997:Time Factors
D000911:Antibodies, Monoclonal; D000961:Antilymphocyte Serum; D007166:Immunosuppressive Agents; D015375:Receptors, Interleukin-2