Contribution of androgens to chronic allograft nephropathy is mediated by dihydrotestosterone

Kidney Int. 2001 Nov;60(5):1955-63. doi: 10.1046/j.1523-1755.2001.00007.x.


Background: Donor and recipient gender influence long-term allograft outcome after kidney transplantation. Sex hormones are likely to contribute to these gender-related differences. The present study investigated the role of androgens and their inhibition on the development of chronic allograft nephropathy.

Methods: Male or female Fisher (F344) kidneys were orthotopically transplanted into intact male Lewis recipients. Animals were treated either with testosterone, the antiandrogen flutamide, the 5alpha-reductase inhibitor finasteride, or vehicle. Twenty weeks after transplantation animals were harvested for histology, immunohistology, and molecular analysis.

Results: Testosterone treatment resulted in an increased proteinuria as well as profound glomerulosclerosis, tubulointerstitial fibrosis, and mononuclear cell infiltration that paralleled enhanced intragraft mRNA levels of transforming growth factor-beta (TGF-beta) and platelet-derived growth factor-A and -B chain (PDGF-A and -B). In contrast, flutamide and finasteride reduced glomerulosclerosis as well as the inflammatory cell infiltration associated with decreased TGF-beta, PDGF-A, and -B chain mRNA expression. No gender-related donor differences were noted between the groups.

Conclusions: Our data suggest that dihydrotestosterone mediates the adverse effects of androgens on chronic allograft nephropathy. The inhibition of androgens improves long-term allograft outcome after kidney transplantation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Androgen Antagonists / pharmacology*
  • Animals
  • Chronic Disease
  • Dihydrotestosterone / toxicity*
  • Female
  • Flutamide / pharmacology
  • Kidney Diseases / etiology*
  • Kidney Diseases / prevention & control
  • Kidney Transplantation / adverse effects*
  • Male
  • Rats
  • Rats, Inbred F344
  • Sex Factors
  • Transplantation, Homologous


  • Androgen Antagonists
  • Dihydrotestosterone
  • Flutamide