Open AccessmTOR inhibitors and risk of chronic antibody‐mediated rejection after kidney transplantation: where are we now?
Author(s) -
Grimbert Philippe,
Thaunat Olivier
Publication year - 2017
Publication title -
transplant international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.998
H-Index - 82
eISSN - 1432-2277
pISSN - 0934-0874
DOI - 10.1111/tri.12975
Subject(s) - medicine , immunosuppression , calcineurin , pi3k/akt/mtor pathway , kidney transplantation , transplantation , sirolimus , regimen , everolimus , adverse effect , immunology , pharmacology , oncology , signal transduction , biology , biochemistry
Summary Antibody‐mediated rejection ( AMR ) usually starts with generation of donor‐specific anti‐ HLA antibodies ( DSA s), arising from a B‐cell response to antigen recognition. In vitro and preclinical data demonstrate that mammalian target of rapamycin ( mTOR ) inhibition attenuates the mTOR ‐mediated intracellular signaling pathway involved in AMR ‐related kidney damage. The limited available data from immunological studies in kidney transplant patients, however, have not shown such effects in vivo . In terms of clinical immunosuppression, the overriding influence on rates of de novo DSA (dn DSA ) or AMR —regardless of the type of regimen—is patient adherence. To date, limited data from patients given mTOR inhibitor therapy with adequate concurrent immunosuppression, such as reduced‐exposure calcineurin inhibitor ( CNI ) therapy, have not shown an adverse effect on the risk of dn DSA or AMR . Early switch to an mTOR inhibitor (<6–12 months post‐transplant) in a CNI ‐free regimen, in contrast, can increase the risk of dn DSA , especially if adjunctive therapy is inadequate. Late conversion to CNI ‐free therapy with mTOR inhibition does not appear to affect the risk of dn DSA . More data, from prospective studies, are required to fully understand that association between use of mTOR inhibitors with different types of concomitant therapy and risk of dnDSA and AMR.