Sirolimus versus cyclosporine therapy increases circulating regulatory T cells, but does not protect renal transplant patients given alemtuzumab induction from chronic allograft injury

Piero Ruggenenti, Norberto Perico, Eliana Gotti, Paolo Cravedi, Vivette D'Agati, Elena Gagliardini, Mauro Abbate, Flavio Gaspari, Dario Cattaneo, Marina Noris, Federica Casiraghi, Marta Todeschini, Daniela Cugini, Sara Conti, Giuseppe Remuzzi

Research output: Contribution to journalArticlepeer-review

Abstract

BACKGROUND. In kidney transplant recipients with alemtuzumab induction maintained on mycophenolate mofetil (MMF) immunosuppression, sirolimus (SRL) promotes significant expansion of circulating CD4CD25 regulatory T cells (Treg). This might translate into more effective protection against chronic graft injury compared to cyclosporin A (CsA), which, in the same clinical setting, does not affect Treg. METHODS. To assess this hypothesis, in the extension of a single-center, prospective, randomized, open, blind endpoint study aimed to assess the effect of low-dose SRL or CsA on circulating Treg, we compared the outcomes of renal transplant recipients on SRL (n=11) or CsA (n=10) by per-protocol biopsies and serial measurements of glomerular filtration rate (GFR), renal plasma flow (RPF), and 24-hour proteinuria over 30 months posttransplant. RESULTS. Despite 4-fold higher CD4CD25 Treg counts (22.1±12.2% vs. 5.7±4.2% of CD3CD4 T cells), SRL-treated patients, compared to CsA-treated patients, had a significantly higher tubular C4d staining score (1.1±0.6 vs. 0.2±0.3, P

Original languageEnglish
Pages (from-to)956-964
Number of pages9
JournalTransplantation
Volume84
Issue number8
DOIs
Publication statusPublished - Oct 2007

Keywords

  • Chronic allograft injury
  • Cyclosporine
  • Kidney transplantation
  • Sirolimus
  • T regulatory cells

ASJC Scopus subject areas

  • Transplantation
  • Immunology

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