Molecular comparison of calcineurin inhibitor-induced fibrogenic responses in protocol renal transplant biopsies

Marian C. Roos-van Groningen*, Eduard M. Scholten, Patrick M. Lelieveld, Ajda T. Rowshani, Hans J. Baelde, Ingeborg M. Bajema, Sandrine Florquin, Frederike J. Bemelman, Emile de Heer, Johan W. de Fijter, Jan A. Bruijn, Michael Eikmans

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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Abstract

The calcineurin inhibitor cyclosporine (CsA) induces a fibrogenic response that may lead to scarring of the renal allograft. This study investigated whether tacrolimus, a novel calcineurin inhibitor, exerts fibrogenic effects to a similar extent. Sixty patients were enrolled in a randomized study: 29 received CsA, and 31 received tacrolimus. Patients were subjected to tailored exposure-controlled calcineurin inhibitor regimens. Protocol biopsies were obtained at the time of transplantation and 6 and 12 mo after transplantation. Cortical TGF-beta and collagens alpha 1(I) and alpha 1(III) mRNA steady-state levels were determined with real-time PCR. The extent of protein deposition of TGF-beta, alpha-smooth muscle actin, and interstitial collagens in the renal cortex was quantified with computer-assisted image analysis. The extent of interstitial collagen deposition measured with Sirius red and the accumulation of alpha-smooth muscle actin and TGF-beta protein after 6 and 12 mo were similar for both immunosuppressive regimens. mRNA levels of TGF-beta and collagens alpha 1(I) and alpha 1(III) were not significantly different in the treatment groups either. It is concluded that the fibrogenic response in renal allografts is similar in patients who receive CsA-based regimens and patients who receive tacrolimus-based regimens.

Original languageEnglish
Pages (from-to)881-888
Number of pages8
JournalJournal of the American Society of Nephrology
Volume17
Issue number3
DOIs
Publication statusPublished - Mar-2006
Event38th Annual Meeting of the American-Society-of-Nephrology - , Panama
Duration: 8-Nov-200513-Nov-2005

Keywords

  • GROWTH-FACTOR-BETA
  • CHRONIC REJECTION
  • MESSENGER-RNA
  • TGF-BETA
  • TRANSFORMING GROWTH-FACTOR-BETA-1
  • CYCLOSPORINE NEPHROTOXICITY
  • INTERSTITIAL FIBROSIS
  • ALLOGRAFT NEPHROPATHY
  • EXTRACELLULAR-MATRIX
  • GRAFT-SURVIVAL

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