TGF-β1 Expression in Kidney Allograft Protocol Biopsies during Cyclosporine: a Therapy

Background TGF-β1 expression has been described to increase along with time from transplantation and has also been linked to allograft dysfunction and toxic effects of cyclosporine. Our aim was to correlate intragraft TGF-β1 expression with cyclosporine exposure after kidney transplantation. Methods Altogether 53 kidney allograft protocol biopsies from 42 patients on a low-dose cyclosporine-based regimen obtained at 3, 6, and 12 months were classified according to Banff and the chronic allograft damage index (CADI). TGF-β1 expression in tubules, glomeruli, vessels, and inflammatory cells was semi-quantitatively scored and correlated with cyclosporine concentrations (C0 and C2), CADI, and graft function. Results TGF-β1 expression was mildly increased along time from transplantation, but the results were not statistically significant. TGF-β1 expression was neither related to CADI nor to the use of ACE inhibitors/ARB. TGF-β1 expression in the kidney was not correlated with C0 or C2 levels or kidney graft function during follow-up. Conclusion In protocol biopsies from patients on low-dose cyclosporine regimen, expression of TGB-β1 was not significantly increased along time since transplantation, and did not correlate with cyclosporine exposure. Our findings suggest that the toxic effects of low-dose cyclosporine on TGF-β expression may be milder than previously thought.

[1]  T. Paavonen,et al.  Is Cystatin C more sensitive than creatinine in detecting early chronic allograft nephropathy? , 2008, Clinical nephrology.

[2]  J. Carstens.  Three-years experience with Neoral C2 monitoring adjusted to a target range of 500–600 ng/ml in long-term renal transplant recipients receiving dual immunosuppressive therapy , 2008, Scandinavian journal of urology and nephrology.

[3]  L. Hilbrands,et al.  Reduced exposure to calcineurin inhibitors in renal transplantation. , 2008, The New England journal of medicine.

[4]  S. Roberts,et al.  TGF-beta1 in chronic allograft nephropathy following renal transplantation. , 2007, Journal of nephrology.

[5]  E. Bottinger.  TGF-β in renal injury and disease , 2007 .

[6]  E. Böttinger.  TGF-beta in renal injury and disease. , 2007, Seminars in nephrology.

[7]  H. Volk,et al.  TGF-β1 mRNA upregulation influences chronic renal allograft dysfunction , 2006 .

[8]  H. Volk,et al.  TGF-beta1 mRNA upregulation influences chronic renal allograft dysfunction. , 2006, Kidney international.

[9]  O. Viklicky,et al.  The effect of different immunosuppressive regimens on TGF‐β1 expression in kidney transplant patients , 2005, Transplant international : official journal of the European Society for Organ Transplantation.

[10]  A. Perkowska-Ptasinska,et al.  Serum TGF-β1 Correlates With Chronic Histopathological Lesions in Protocol Biopsies of Kidney Allograft Recipients , 2005 .

[11]  K. Salmela,et al.  Predictors of renal allograft histologic damage progression. , 2005, Journal of the American Society of Nephrology : JASN.

[12]  M. Haberal,et al.  TGF-β1 Expression in Renal Allograft Rejection and Cyclosporine A Toxicity , 2004, Transplantation.

[13]  A. Perkowska-Ptasinska,et al.  Serum TGF-beta1 correlates with chronic histopathological lesions in protocol biopsies of kidney allograft recipients. , 2005, Transplantation proceedings.

[14]  F. Schena,et al.  Conversion to C2 monitoring of cyclosporine A exposure in maintenance kidney transplant recipients: results at 3 years. , 2004, American journal of kidney diseases : the official journal of the National Kidney Foundation.

[15]  J. Chapman,et al.  Calcineurin Inhibitor Nephrotoxicity: Longitudinal Assessment by Protocol Histology , 2004, Transplantation.

[16]  K. Midtvedt.  Is C0 better than C2 as a determinant of rejection in renal transplant recipients? , 2004, Kidney international.

[17]  T. Wekerle,et al.  Comparison Between C0 And C2 Monitoring in De Novo Renal Transplant Recipients: Retrospective Analysis of a Single-Center Experience , 2004, Transplantation.

[18]  F. Citterio.  Evolution of the therapeutic drug monitoring of cyclosporine. , 2004, Transplantation proceedings.

[19]  K. Salmela,et al.  Two decades of experience with cyclosporine in renal transplantation in Helsinki. , 2004, Transplantation proceedings.

[20]  O. Viklicky,et al.  TGF-β1 expression and chronic allograft nephropathy in protocol kidney graft biopsy , 2003 .

[21]  Sunjay Jain,et al.  Sequential protocol biopsies from renal transplant recipients show an increasing expression of active TGF β , 2002, Transplant international : official journal of the European Society for Organ Transplantation.

[22]  F. Pan,et al.  High level of TGF-beta in organ transplantation might be due to rejection rather than calcineurin inhibitor medication. , 2002, Transplantation proceedings.

[23]  H. Baelde,et al.  High transforming growth factor-beta and extracellular matrix mRNA response in renal allografts during early acute rejection is associated with absence of chronic rejection. , 2002, Transplantation.

[24]  O. Pankewycz,et al.  Transforming growth factor-beta levels in human allograft chronic fibrosis correlate with rate of decline in renal function. , 1999, Transplantation.

[25]  M. Solé,et al.  Differences between acute and chronic renal graft rejection on immunohistochemical staining of transforming growth factor beta-1. , 1999, Transplantation proceedings.

[26]  V. Cairns,et al.  Transforming growth factor (TGF)-beta mimics and anti-TGF-beta antibody abrogates the in vivo effects of cyclosporine: demonstration of a direct role of TGF-beta in immunosuppression and nephrotoxicity of cyclosporine. , 1999, Transplantation.

[27]  O. Pankewycz,et al.  Increased renal tubular expression of transforming growth factor beta in human allografts correlates with cyclosporine toxicity. , 1996, Kidney international.

[28]  K. Funa,et al.  Increased immunoreactivity of transforming growth factor-β in human kidney transplants , 1996 .