Transforming growth factor-β levels in human allograft chronic fibrosis correlate with rate of decline in renal function

Bulent Cuhaci, Mysore S A Kumar, Roy D. Bloom, Bruce Pratt, Gail Haussman, David A. Laskow, Moona Alidoost, Carolyn Grotkowski, Kathy Cahill, Lavjay Butani, Benjamin C. Sturgill, Oleh G. Pankewycz

Research output: Contribution to journalArticle

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Abstract

Background. Long-term renal transplant function is limited primarily by a progressive scarring process loosely termed 'chronic rejection, chronic allograft nephropathy, or allograft fibrosis.' Although the etiology of transplant fibrosis is uncertain, several possible factors including chronic cyclosporin A (CsA) exposure may contribute to its pathogenesis. CsA stimulates renal fibrosis perhaps through the induction of the potent pro- sclerotic growth factor, transforming growth factor β (TGFβ). Previously, we demonstrated that, in human transplant biopsies, acute CsA toxicity but not acute tubular necrosis is associated with elevated levels of renal TGFβ protein. We now examine whether long-term CsA treatment (>1 year) is associated with elevated levels of intra-allograft TGFβ and whether heightened expression of TGFβ is clinically significant. Methods. Using immunohistochemical techniques, we determined the relative level of expression of intrarenal TGFβ protein in transplant biopsies. We studied biopsies obtained from 40 CsA-treated patients that were diagnosed as having chronic allograft fibrosis. Biopsies were scored as having minimal or high levels of TGFβ. Results. Seventy-two percent of patients expressed high levels of intra-allograft TGFβ. This group of patients lost renal function at an average rate of -19.5 ± 17.3 ml/min/year. In contrast, patients with minimal or no TGFβ expression experienced a decline of only -6.2 ± 4.1 ml/min/year (P = 0.01). Conclusions. These results suggest that the majority of CsA-treated patients with biopsy proven chronic fibrosis have elevated levels of intra-graft TGFβ that correlates with an increased rate of decline in renal function.

Original languageEnglish (US)
Pages (from-to)785-790
Number of pages6
JournalTransplantation
Volume68
Issue number6
DOIs
StatePublished - Sep 27 1999
Externally publishedYes

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Transforming Growth Factors
Allografts
Fibrosis
Kidney
Cyclosporine
Transplants
Biopsy
Cicatrix
Intercellular Signaling Peptides and Proteins
Proteins
Necrosis

ASJC Scopus subject areas

  • Transplantation
  • Immunology

Cite this

Cuhaci, B., Kumar, M. S. A., Bloom, R. D., Pratt, B., Haussman, G., Laskow, D. A., ... Pankewycz, O. G. (1999). Transforming growth factor-β levels in human allograft chronic fibrosis correlate with rate of decline in renal function. Transplantation, 68(6), 785-790. https://doi.org/10.1097/00007890-199909270-00010

Transforming growth factor-β levels in human allograft chronic fibrosis correlate with rate of decline in renal function. / Cuhaci, Bulent; Kumar, Mysore S A; Bloom, Roy D.; Pratt, Bruce; Haussman, Gail; Laskow, David A.; Alidoost, Moona; Grotkowski, Carolyn; Cahill, Kathy; Butani, Lavjay; Sturgill, Benjamin C.; Pankewycz, Oleh G.

In: Transplantation, Vol. 68, No. 6, 27.09.1999, p. 785-790.

Research output: Contribution to journalArticle

Cuhaci, B, Kumar, MSA, Bloom, RD, Pratt, B, Haussman, G, Laskow, DA, Alidoost, M, Grotkowski, C, Cahill, K, Butani, L, Sturgill, BC & Pankewycz, OG 1999, 'Transforming growth factor-β levels in human allograft chronic fibrosis correlate with rate of decline in renal function', Transplantation, vol. 68, no. 6, pp. 785-790. https://doi.org/10.1097/00007890-199909270-00010
Cuhaci, Bulent ; Kumar, Mysore S A ; Bloom, Roy D. ; Pratt, Bruce ; Haussman, Gail ; Laskow, David A. ; Alidoost, Moona ; Grotkowski, Carolyn ; Cahill, Kathy ; Butani, Lavjay ; Sturgill, Benjamin C. ; Pankewycz, Oleh G. / Transforming growth factor-β levels in human allograft chronic fibrosis correlate with rate of decline in renal function. In: Transplantation. 1999 ; Vol. 68, No. 6. pp. 785-790.
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T1 - Transforming growth factor-β levels in human allograft chronic fibrosis correlate with rate of decline in renal function

AU - Cuhaci, Bulent

AU - Kumar, Mysore S A

AU - Bloom, Roy D.

AU - Pratt, Bruce

AU - Haussman, Gail

AU - Laskow, David A.

AU - Alidoost, Moona

AU - Grotkowski, Carolyn

AU - Cahill, Kathy

AU - Butani, Lavjay

AU - Sturgill, Benjamin C.

AU - Pankewycz, Oleh G.

PY - 1999/9/27

Y1 - 1999/9/27

N2 - Background. Long-term renal transplant function is limited primarily by a progressive scarring process loosely termed 'chronic rejection, chronic allograft nephropathy, or allograft fibrosis.' Although the etiology of transplant fibrosis is uncertain, several possible factors including chronic cyclosporin A (CsA) exposure may contribute to its pathogenesis. CsA stimulates renal fibrosis perhaps through the induction of the potent pro- sclerotic growth factor, transforming growth factor β (TGFβ). Previously, we demonstrated that, in human transplant biopsies, acute CsA toxicity but not acute tubular necrosis is associated with elevated levels of renal TGFβ protein. We now examine whether long-term CsA treatment (>1 year) is associated with elevated levels of intra-allograft TGFβ and whether heightened expression of TGFβ is clinically significant. Methods. Using immunohistochemical techniques, we determined the relative level of expression of intrarenal TGFβ protein in transplant biopsies. We studied biopsies obtained from 40 CsA-treated patients that were diagnosed as having chronic allograft fibrosis. Biopsies were scored as having minimal or high levels of TGFβ. Results. Seventy-two percent of patients expressed high levels of intra-allograft TGFβ. This group of patients lost renal function at an average rate of -19.5 ± 17.3 ml/min/year. In contrast, patients with minimal or no TGFβ expression experienced a decline of only -6.2 ± 4.1 ml/min/year (P = 0.01). Conclusions. These results suggest that the majority of CsA-treated patients with biopsy proven chronic fibrosis have elevated levels of intra-graft TGFβ that correlates with an increased rate of decline in renal function.

AB - Background. Long-term renal transplant function is limited primarily by a progressive scarring process loosely termed 'chronic rejection, chronic allograft nephropathy, or allograft fibrosis.' Although the etiology of transplant fibrosis is uncertain, several possible factors including chronic cyclosporin A (CsA) exposure may contribute to its pathogenesis. CsA stimulates renal fibrosis perhaps through the induction of the potent pro- sclerotic growth factor, transforming growth factor β (TGFβ). Previously, we demonstrated that, in human transplant biopsies, acute CsA toxicity but not acute tubular necrosis is associated with elevated levels of renal TGFβ protein. We now examine whether long-term CsA treatment (>1 year) is associated with elevated levels of intra-allograft TGFβ and whether heightened expression of TGFβ is clinically significant. Methods. Using immunohistochemical techniques, we determined the relative level of expression of intrarenal TGFβ protein in transplant biopsies. We studied biopsies obtained from 40 CsA-treated patients that were diagnosed as having chronic allograft fibrosis. Biopsies were scored as having minimal or high levels of TGFβ. Results. Seventy-two percent of patients expressed high levels of intra-allograft TGFβ. This group of patients lost renal function at an average rate of -19.5 ± 17.3 ml/min/year. In contrast, patients with minimal or no TGFβ expression experienced a decline of only -6.2 ± 4.1 ml/min/year (P = 0.01). Conclusions. These results suggest that the majority of CsA-treated patients with biopsy proven chronic fibrosis have elevated levels of intra-graft TGFβ that correlates with an increased rate of decline in renal function.

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