Abstract
920 Transforming growth factor-beta (TGF-β) is produced by a variety of cells including several renal cell types. TGF-β is a growth-regulating protein that has been shown to enhance collagen production in cultured cells. High cyclosporine-A (CsA) levels might lead to nephrotoxicity with increasing TGF-β and collagen synthesis in renal transplant recipients. We hypothesized that local renal TGF-β expression may increase with high circulating CsA levels. Therefore, the current study was designed to determine the TGF-β1 isoform expression in human renal biopsy tissue with high and low CsA levels by immunohistochemical staining (IHCS). Kidney biopsies from nine transplant recipients with chronic allograft nephropathy were obtained before (CsA level: 321±106 ng/ml) and after (CsA level: 141±40 ng/ml) reduction in CsA dosage (time between biopsies: 15.8±0.8 months). TGF-β1 IHCS score (S) (0-4) and positive staining area (%) were significantly decreased in patients with reduction in CsA levels. TGF-β1 was localized in the glomeruli and tubular cells, and was minimally evident in control biopsy specimens (IHCS score 0.2-0.4). Pathological evaluation included percentage expression (%) of interstitial fibrosis and tubular atrophy (FIB), vascular sclerosis (VS), transplant glomerulopathy (TG), and vascular hyalinosis (VH). Serum creatinine (CR, mg/dl) and BUN (mg/dl) levels were also investigated. Mean±SE, *p<.05 vs High CsA group. (Table)TableThese data indicate that chronic reduction in CsA may diminish production of renal TGF-β expression, and results in decreased renal fibrosis and improvement of renal function in patients with chronic allograft nephropathy.
Published Version
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