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

Huseyin Toz1, Sait Sen, Handan Ak Celik

  • 1Division of Nephrology, Ege University School of Medicine, Izmir, Turkey. huseyin.toz@ege.edu.tr

Annals of Transplantation
|July 1, 2011
PubMed
Abstract

Insights

Calcineurin inhibitors (CNI) and mammalian target of rapamycin inhibitors (mTOR-i) have different molecular effects on kidney transplants. Gene expression profiles reveal distinct molecular changes between CNI and mTOR-i treatments, despite similar clinical outcomes.

Area of Science:

  • Nephrology
  • Immunosuppression
  • Molecular Biology

Background:

  • Calcineurin inhibitors (CNI) are associated with chronic nephrotoxicity and reduced kidney allograft survival.
  • Mammalian target of rapamycin inhibitors (mTOR-i) offer an alternative immunosuppression strategy with potentially fewer nephrotoxic effects.
  • The molecular differences between CNI and mTOR-i in kidney transplantation remain unclear.

Purpose of the Study:

  • To investigate the distinct molecular profiles of kidney allografts treated with CNI versus mTOR-i.
  • To compare gene expression patterns in kidney biopsies from patients receiving different immunosuppressive regimens.

Main Methods:

  • Analysis of kidney graft protocol biopsies from patients treated with CNI (n=4) or mTOR-i (n=4).
  • Inclusion of a control group of 5 biopsies from zero-hour implantation.
  • Gene expression profiling using Affymetrix® GeneChip U133 plus 2.0 Array.

Main Results:

  • Compared to controls, 64 genes were up-regulated and 119 down-regulated in the CNI and mTOR-i groups combined.
  • A total of 29 genes were up-regulated in the CNI group relative to the mTOR-i group.
  • 101 genes were up-regulated in the mTOR-i group compared to the CNI group.

Conclusions:

  • Different immunosuppressive strategies, CNI and mTOR-i, induce distinct gene expression profiles in kidney allografts.
  • These molecular differences exist despite similar clinical courses and histopathological findings.
  • Understanding these molecular distinctions may inform future immunosuppressive treatment strategies in kidney transplantation.

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