Fibrosis-associated gene expression in renal transplant glomeruli after acute renal allograft rejection.
BACKGROUND
Acute allograft rejection is thought to be a risk factor for chronic allograft nephropathy, the cardinal features of which are vasculopathy, interstitial fibrosis and glomerulosclerosis. Fibrosis-associated genes might act as ad interim surrogate markers for chronic allograft nephropathy. The aim of this study was to determine mRNA expression of fibrosis-associated genes in glomeruli plucked from protocol renal transplant biopsies, in patients with or without a history of acute rejection.


METHODS
A consecutive series of 52 patients (31 male, 21 female) was assessed. Donor categories were cadaveric, living related or asystolic. Transplant recipients received either cyclosporin- or tacrolimus-based immunosuppression. Patients routinely underwent percutaneous needle-core renal transplant biopsy at 1 week, and 3 and 6 months. Acute rejection episodes were confirmed histologically and treated with intravenous methylprednisolone, or antithymocyte globulin if steroid resistant. Individual glomeruli were plucked and total mRNA was extracted. Fibrosis-associated genes were amplified by reverse transcriptase-polymerase chain reaction (PCR) and quantified by enzyme-linked immunosorbent assay.


RESULTS
The expression of both collagen type III (mean 0.42 versus 0.31 arbitrary units of PCR products corrected for a housekeeping gene) and collagen IV (mean 0.46 versus 0.42 arbitrary units) at 6 months did not differ between recipients who experienced acute rejection episodes and those who were free from rejection. There was also no significant difference between groups in terms of mRNA expression of collagen IValpha2, matrix metalloproteinase 2, tissue inhibitor of matrix metalloproteinases 1 and 2, transforming growth factor beta or tenascin.


CONCLUSIONS
These results suggest that acute rejection episodes do not increase the expression of fibrosis-associated genes in glomeruli from renal transplant biopsies.
Brook
N R
NR
Division of Transplant Surgery, University of Leicester, Leicester General Hospital, Gwendolen Road, Leicester LE5 4PW, UK. nicholasbrook@fastmail.fm
White
S A
SA
Waller
J R
JR
Bicknell
G R
GR
Nicholson
M L
ML
D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D016572:Cyclosporine / Q000627:therapeutic use; D005260:Female; D005355:Fibrosis / Q000235:genetics; D015870:Gene Expression; D006084:Graft Rejection; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007676:Kidney Failure, Chronic / Q000503:physiopathology / Q000601:surgery; D007678:Kidney Glomerulus / Q000473:pathology; D016030:Kidney Transplantation / Q000379:methods / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000378:metabolism; D016559:Tacrolimus / Q000627:therapeutic use; D015291:Transforming Growth Factors / Q000378:metabolism; D014184:Transplantation, Homologous
D007166:Immunosuppressive Agents; D012333:RNA, Messenger; D015291:Transforming Growth Factors; D016572:Cyclosporine; D016559:Tacrolimus