Renal Allograft Function and Histology Following Switching From A Tacrolimus to Sirolimus (SRL)-Based Immunosuppression-
Status:
Terminated
Trial end date:
2014-12-01
Target enrollment:
Participant gender:
Summary
The investigators hypothesize that Tacrolimus (Tac) withdrawal from a Tac, MMF and steroid
based triple therapy regimen leads to long term improved/stabilized graft function
(glomerular filtration rate, GFR) primarily as a consequence of halting CNI-induced
fibrogenetic processes that mediate loss of functioning renal tissue. The investigators
further hypothesize that the underlying fibrotic mechanism is mediated by pathophysiologic
processes that promote epithelial to mesenchymal transition (EMT) (mediated by TGF- ƒÒ) and
that early therapeutic intervention may reverse this process (mediated by BMP-7)4.
To address these hypotheses the investigators propose the following clinical and mechanistic
aims:
The investigators will test the hypothesis that switching from Tac to SRL in a Tac based
triple therapy regimen with MMF and steroids in living and or deceased donor renal transplant
recipients leads to improvement in allograft structure and function at 2 years
post-transplantation.
The investigators will test this hypothesis in an open label controlled trial where stable
renal allograft recipients on Tac, MMF, prednisone maintenance immunosuppression will undergo
renal biopsy at 3-4 months post-transplantation and will be randomized to either a) Remain on
Tac, MMF and prednisone (CNI-maintenance) or b) switch the Tac to SRL and continue MMF and
prednisone. The investigators will then compare biopsy derived measures of allograft fibrosis
(CADI, Sirius Red, Banff Chronicity Index) and GFR in the two groups