期刊
TRANSPLANTATION
卷 84, 期 8, 页码 956-964出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/01.tp.0000284808.28353.2c
关键词
T regulatory cells; kidney transplantation; chronic allograft injury; Sirolimus; cyclosporine.
Background. In kidney transplant recipients with alemtuzumab induction maintained on mycophenolate mofetil (MMF) immunosuppression, sirolimus (SRL) promotes significant expansion of circulating CD4(+)CD25(high) 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 CD4(+)CD25(high) Treg counts (22.1 +/- 12.2% vs. 5.7 +/- 4.2% of CD3+CD4+ T cells), SRLtreated patients, compared to CsA-treated patients, had a significantly higher tubular C4d staining score (1.1 +/- 0.6 vs. 0.2 +/- 0.3, P < 0.01), with nonsignificant trends to higher chronic allograft damage index score (5.6 +/- 2.4 vs. 3.7 +/- 3.3), faster GFR (-2.92 +/- 0.33 vs. -0.28 +/- 0.44 mi/min/1.73m(2) per year), and RPF (- 10.80 +/- 5.45 vs. -1.86 3.09 ml/min/ 1.73 m(2) per year) decline, and more clinical proteinuria (n = 6 vs. 4). There was no significant correlation between Treg counts and any considered outcome variable in the study group as a whole and within each cohort. Conclusions. These data suggest that, despite enhanced Treg expression, low-dose SRL combined to alemtuzumab induction and MMF-based steroid-free maintenance therapy, does not appreciably protect renal transplant recipients from chronic allograft injury and dysfunction.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据