Calcineurin inhibitor withdrawal after renal transplantation with alemtuzumab: Clinical outcomes and effect on T-regulatory cells

J. Pascual, D. Bloom, J. Torrealba, R. Brahmbhatt, Z. Chang, H. W. Sollinger, S. J. Knechtle

Research output: Contribution to journalArticlepeer-review

61 Scopus citations

Abstract

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 Patients withdrawn from CNI after alemtuzumab trend toward a higher rejection rate, but most patients can be weaned from a CNI using this regimen.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.

Original languageEnglish (US)
Pages (from-to)1529-1536
Number of pages8
JournalAmerican Journal of Transplantation
Volume8
Issue number7
DOIs
StatePublished - Jul 2008

Keywords

  • Alemtuzumab
  • CD4+CD25+ T cells
  • CNI nephrotoxicity
  • Calcineurin inhibitor agents
  • Calculated glomerular filtration rate
  • Campath-1H
  • Chronic nephrotoxicity
  • Clinical kidney transplantation
  • Foxp3
  • Immunosuppression withdrawal T-regulatory cells

ASJC Scopus subject areas

  • Immunology and Allergy
  • Transplantation
  • Pharmacology (medical)

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