Early activation of fibrogenesis in transplanted kidneys: a study on serial renal biopsies.
OBJECTIVE
In kidney transplants, the renin-angiotensin system (RAS) is involved in systemic and local changes that may induce fibrosis. Our aim was to use gene expression and immunohistochemical analysis to investigate the RAS and several factors involved in the fibrogenic cascade in allograft biopsies.


METHODS
We considered 43 donor biopsies (T0), 18 biopsies obtained for diagnostic purposes (Td) and 24 protocol biopsies (Tp) taken 2 months after transplantation in patients with stable renal function. Morphometric alpha SMA and TGF beta 1 analysis, and Masson's Trichrome staining were performed. mRNA levels of angiotensinogen, renin, ACE, AT1-R, AT2-R, TGF beta 1, BMP-7, Coll III, fibronectin and alpha SMA were analyzed by real-time RT/PCR. MDRD a year after the transplant was also considered.


RESULTS
Significantly higher levels of AT1-R and alpha SMA transcripts were found in Tp than in T0. Regression analysis showed significant TGF beta 1-independent positive correlations between RAS and matrix components in T0 and Tp, but more evident in Tp, where a positive correlation between TGF beta 1 and Masson's Trichrome stained areas was also seen.


CONCLUSIONS
Our results suggest that RAS and TGF beta 1-related fibrogenic loops are activated as early as 2 months after kidney transplantation.
Del Prete
Dorella
D
Nephrology Division, Department of Medical and Surgical Sciences, University of Padova, via Giustiniani 2, 35128 Padova, Italy. dorella.delprete@unipd.it
Ceol
Monica
M
Anglani
Franca
F
Vianello
Daniela
D
Tiralongo
Emilia
E
Valente
Marialuisa
M
Graziotto
Romina
R
Bonfante
Luciana
L
Scaparrotta
Giuseppe
G
Furian
Lucrezia
L
Rigotti
Paolo
P
Gambaro
Giovanni
G
D'Angelo
Angela
A
D000328:Adult; D001706:Biopsy; D005355:Fibrosis; D015870:Gene Expression; D020869:Gene Expression Profiling; D006801:Humans; D007150:Immunohistochemistry; D007668:Kidney / Q000378:metabolism / Q000473:pathology; D016030:Kidney Transplantation / Q000473:pathology*; D008875:Middle Aged; D012333:RNA, Messenger / Q000032:analysis; D012084:Renin-Angiotensin System / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D053773:Transforming Growth Factor beta1 / Q000235:genetics* / Q000378:metabolism
D012333:RNA, Messenger; D053773:Transforming Growth Factor beta1