TY - JOUR
T1 - Calcineurin inhibitor withdrawal after renal transplantation with alemtuzumab
T2 - Clinical outcomes and effect on T-regulatory cells
AU - Pascual, J.
AU - Bloom, D.
AU - Torrealba, J.
AU - Brahmbhatt, R.
AU - Chang, Z.
AU - Sollinger, H. W.
AU - Knechtle, S. J.
N1 - Copyright:
Copyright 2011 Elsevier B.V., All rights reserved.
PY - 2008/7
Y1 - 2008/7
N2 - To address the results of calcineurin inhibitor (CNI) withdrawal after alemtuzumab induction relative to CNI continuation, we performed a pilot randomized clinical trial in renal allograft recipients on CNI, a mycophenolic acid derivative and steroids after the first 2 months posttransplantation. Forty patients were randomized to taper off CNI or to maintain it, and followed for at least 1 year. Four patients in the withdrawal group were treated for acute rejection while no patient received antirejection treatment in the control group. Two control patients withdrew CNI due to nephrotoxicity. Estimated GFR was similar in both groups after 1 year. Flow cytometry of CD4 +CD25+CTLA-4+FoxP3+ regulatory T cells (Treg) demonstrated a significant increase in Treg percentages in the peripheral blood of alemtuzumab-treated patients on CNI early postransplant. Furthermore, the increased Treg percentages in the withdrawal cohort were unchanged at month 6 postenrollment, whereas they decreased significantly in those patients maintained on CNI. Patients withdrawn from CNI after alemtuzumab trend toward a higher rejection rate, but most patients can be weaned from a CNI using this regimen. With the exception of maintaining increased Treg levels, the benefits are not appreciable in this short follow-up, and a larger randomized trial is justified.
AB - To address the results of calcineurin inhibitor (CNI) withdrawal after alemtuzumab induction relative to CNI continuation, we performed a pilot randomized clinical trial in renal allograft recipients on CNI, a mycophenolic acid derivative and steroids after the first 2 months posttransplantation. Forty patients were randomized to taper off CNI or to maintain it, and followed for at least 1 year. Four patients in the withdrawal group were treated for acute rejection while no patient received antirejection treatment in the control group. Two control patients withdrew CNI due to nephrotoxicity. Estimated GFR was similar in both groups after 1 year. Flow cytometry of CD4 +CD25+CTLA-4+FoxP3+ regulatory T cells (Treg) demonstrated a significant increase in Treg percentages in the peripheral blood of alemtuzumab-treated patients on CNI early postransplant. Furthermore, the increased Treg percentages in the withdrawal cohort were unchanged at month 6 postenrollment, whereas they decreased significantly in those patients maintained on CNI. Patients withdrawn from CNI after alemtuzumab trend toward a higher rejection rate, but most patients can be weaned from a CNI using this regimen. With the exception of maintaining increased Treg levels, the benefits are not appreciable in this short follow-up, and a larger randomized trial is justified.
KW - Alemtuzumab
KW - CD4+CD25+ T cells
KW - CNI nephrotoxicity
KW - Calcineurin inhibitor agents
KW - Calculated glomerular filtration rate
KW - Campath-1H
KW - Chronic nephrotoxicity
KW - Clinical kidney transplantation
KW - Foxp3
KW - Immunosuppression withdrawal T-regulatory cells
UR - http://www.scopus.com/inward/record.url?scp=47249132479&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=47249132479&partnerID=8YFLogxK
U2 - 10.1111/j.1600-6143.2008.02260.x
DO - 10.1111/j.1600-6143.2008.02260.x
M3 - Article
C2 - 18510645
AN - SCOPUS:47249132479
SN - 1600-6135
VL - 8
SP - 1529
EP - 1536
JO - American Journal of Transplantation
JF - American Journal of Transplantation
IS - 7
ER -