Abstract
228 TGF-β is a growth-regulating protein that has been shown to enhance collagen production in vivo and in vitro. Overproduction of TGF-β can lead to renal damage by increasing fibrosis and may be important in the pathogenesis of chronic allograft nephropathy. High cyclosporine (CSA) levels might cause of worsen chronic renal injury by increasing TGF-β and collagen synthesis. Therefore, the current study was designed to determine the TGF-β1 isoform expression in human renal biopsy tissue by immunohistochemical staining (IHCS) in 5 patients with biopsy proven chronic allograft nephropathy and no evidence of acute rejection before and after a 50% reduction in CSA levels and addition of 1g bid of mycophenolate mofetil(MMF). Interval between biopsies was 13.7 ± 2 months. Mean CSA levels were reduced from 200 to 100 ng/ml (12 hour trough TDX assay). TGF-β1 IHCS staining score (0-4) and positive staining area (+%) were significantly decreased in 4 of 5 patients with reduction in CSA levels. TGF-β1 predominately localized in the proximal tubular region, and was minimally evident in control biopsy specimens (IHCS 0.1-0.2).TableThese data suggest that reduction in CSA and addition of MMF may diminish production of TGF-β and result in decreased collagen synthesis and stabilization or improvement in fibrosis in kidney tissue of patients with chronic allograft nephropathy.
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