Molecular comparison of calcineurin inhibitor-induced fibrogenic responses in protocol renal transplant biopsies.
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 alpha1(I) and alpha1(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 alpha1(I) and alpha1(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.
Leiden University Medical Center, Department of Pathology, Building 1, L1-Q, PO Box 9600, 2300 RC Leiden, The Netherlands. m.c.roos_van_groningen@lumc.nl
Marian C
MC
Roos-van Groningen
Eduard M
EM
Scholten
Patrick M
PM
Lelieveld
Ajda T
AT
Rowshani
Hans J
HJ
Baelde
Ingeborg M
IM
Bajema
Sandrine
S
Florquin
Frederike J
FJ
Bemelman
Emile
E
de Heer
Johan W
JW
de Fijter
Jan A
JA
Bruijn
Michael
M
Eikmans
D000328:Adult; D015415:Biomarkers / Q000032:analysis*; D001707:Biopsy, Needle; D003094:Collagen / Q000032:analysis / Q000378:metabolism; D016572:Cyclosporine / Q000009:adverse effects / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005355:Fibrosis / Q000453:epidemiology / Q000473:pathology*; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000517:prevention & control; D006085:Graft Survival; D006801:Humans; D007150:Immunohistochemistry; D016030:Kidney Transplantation / Q000009:adverse effects / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D011336:Probability; D012333:RNA, Messenger / Q000032:analysis; D012016:Reference Values; D018570:Risk Assessment; D016559:Tacrolimus / Q000009:adverse effects / Q000627:therapeutic use*; D016212:Transforming Growth Factor beta / Q000032:analysis / Q000378:metabolism; D014184:Transplantation, Homologous; D016896:Treatment Outcome
D015415:Biomarkers; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D016572:Cyclosporine; D003094:Collagen; D016559:Tacrolimus