TY - JOUR
T1 - Sirolimus versus cyclosporine therapy increases circulating regulatory T cells, but does not protect renal transplant patients given alemtuzumab induction from chronic allograft injury
AU - Ruggenenti, Piero
AU - Perico, Norberto
AU - Gotti, Eliana
AU - Cravedi, Paolo
AU - D'Agati, Vivette
AU - Gagliardini, Elena
AU - Abbate, Mauro
AU - Gaspari, Flavio
AU - Cattaneo, Dario
AU - Noris, Marina
AU - Casiraghi, Federica
AU - Todeschini, Marta
AU - Cugini, Daniela
AU - Conti, Sara
AU - Remuzzi, Giuseppe
PY - 2007/10
Y1 - 2007/10
N2 - 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
AB - 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
KW - Chronic allograft injury
KW - Cyclosporine
KW - Kidney transplantation
KW - Sirolimus
KW - T regulatory cells
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U2 - 10.1097/01.tp.0000284808.28353.2c
DO - 10.1097/01.tp.0000284808.28353.2c
M3 - Article
C2 - 17989600
AN - SCOPUS:37349080895
VL - 84
SP - 956
EP - 964
JO - Transplantation
JF - Transplantation
SN - 0041-1337
IS - 8
ER -