Aims: The profibrotic cytokine transforming growth factor beta (TGF-β1) is believed to play a key... more Aims: The profibrotic cytokine transforming growth factor beta (TGF-β1) is believed to play a key role in the development of chronic graft nephropathy (CGN); however, the aetiopathological evidence for this relationship requires clarification. The aim of this study was to determine the donor and recipient TGF-β1 genotypes and to quantify sequential changes in TGF-β1 message and protein expression in relation to the development of CGN.Methods: Polymorphisms in the promotor region (−800, −509, aa10) of the TGF-β gene were determined using PCR-SSP in 40 donor/recipient pairings. Protocol renal biopsies (0, 3, 6 and 12 months) were subjected to histological examination (Banff grading) and real-time quantitative PCR. Plasma TGF-β levels (total and active) were determined using a commercially available ELISA.Results: Statistically significant (P < 0.05) stepwise increases were observed for plasma total TGF-β levels and TGF-β mRNA compared to baseline at 3, 6 and 12 months. The plasma TGF-β1 was higher in patients with CGN at all assessment points and CGN appeared to be linked to the presence of the PP polymorphism at amino acid 10 in the donor DNA.Conclusions: TGF-β1 is up-regulated at protein and mRNA levels during the first year following cadaveric renal transplantation and the effect of ‘high producer’ gene polymorphisms may also be important. This up-regulation of TGF-β1 in plasma may provide a novel noninvasive means of identifying early fibrotic damage before it becomes clinically apparent thus allowing an opportunity for intervention and salvage of otherwise fated allografts.
Aims: The profibrotic cytokine transforming growth factor beta (TGF-β1) is believed to play a key... more Aims: The profibrotic cytokine transforming growth factor beta (TGF-β1) is believed to play a key role in the development of chronic graft nephropathy (CGN); however, the aetiopathological evidence for this relationship requires clarification. The aim of this study was to determine the donor and recipient TGF-β1 genotypes and to quantify sequential changes in TGF-β1 message and protein expression in relation to the development of CGN.Methods: Polymorphisms in the promotor region (−800, −509, aa10) of the TGF-β gene were determined using PCR-SSP in 40 donor/recipient pairings. Protocol renal biopsies (0, 3, 6 and 12 months) were subjected to histological examination (Banff grading) and real-time quantitative PCR. Plasma TGF-β levels (total and active) were determined using a commercially available ELISA.Results: Statistically significant (P < 0.05) stepwise increases were observed for plasma total TGF-β levels and TGF-β mRNA compared to baseline at 3, 6 and 12 months. The plasma TGF-β1 was higher in patients with CGN at all assessment points and CGN appeared to be linked to the presence of the PP polymorphism at amino acid 10 in the donor DNA.Conclusions: TGF-β1 is up-regulated at protein and mRNA levels during the first year following cadaveric renal transplantation and the effect of ‘high producer’ gene polymorphisms may also be important. This up-regulation of TGF-β1 in plasma may provide a novel noninvasive means of identifying early fibrotic damage before it becomes clinically apparent thus allowing an opportunity for intervention and salvage of otherwise fated allografts.
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