Calcineurin inhibitor-based and free regimens have distinct gene expression patterns in subclinical graft fibrosis

Abstract

Chronic nephrotoxic effects of calcineurin inhibitors may be responsible for late allograft dysfunction and reduced allograft half-life. Mammalian target of rapamycin inhibitors (mTOR-i's), a newer class of immunosuppressant, do not have the chronic nephrotoxic effects shown with calcineurin inhibitors (CNI). Whether these drug classes have distinct features at the molecular level is not clear. Difference in gene expression profiles of kidney graft protocol biopsies from patients treated with CNI or mTOR-i's were investigated. Biopsies from patients using CNI (n=4) and mTOR-i-based treatments (n=4) were analyzed. The control group consisted of 5 biopsies obtained at the time of implantation (zero hour). Microarray hybridization was performed using the Affymetrix® GeneChip U133 plus 2.0 Array. In the CNI and mTOR-i groups, 64 up-regulated and 119 down-regulated genes were found compared to control subjects. A total of 29 genes in the CNI group and 101 genes in the mTOR-i group were up-regulated compared to each other. Despite similar clinical courses and histopathological appearances, different treatment strategies cause different gene expression profiles in kidney transplantation.