Dialysis – Transplantation
Kidney International (1999) 55, 2011–2020; doi:10.1046/j.1523-1755.1999.00441.x
Sex hormones and gender-related differences: Their influence on chronic renal allograft rejection
Veronika Müller, Attila Szabó, Ondrej Viklicky, Isabell Gaul, Stefan Pörtl, Thomas Philipp and Uwe W Heemann
Departments of Nephrology and Endocrinology, University Hospital, Essen, Germany, and Semmelweis Medical University, Budapest, Hungary
Correspondence: Uwe Heemann, M.D., NTP-Ambulanz, Universitätsklinikum Essen, Hufelandstr. 55., 45122 Essen, Germany. E-mail: uwe.heemann@uni-essen.de
Received 28 May 1998; Revised 11 December 1998; Accepted 11 December 1998.
Abstract
Sex hormones and gender-related differences: Their influence on chronic renal allograft rejection.
Background
Renal hemodynamics and immune responses differ between males and females. Thus, sex hormones and genetically determined gender differences may determine the process of chronic rejection to some extent.
Methods
Female (F) or male (M) F344 kidneys were orthotopically transplanted into ovariectomized female Lewis recipients and were treated for 16 weeks with either estradiol, testosterone, or vehicle.
Results
Testosterone treatment resulted in increased urinary protein excretion independently of the donor gender, as well as extended glomerular sclerosis, interstitial fibrosis, and severe vascular lesions. Additionally, mononuclear cell infiltration was most pronounced in these animals, in parallel to an increased expression of intercellular adhesion molecule-1 (ICAM-1), fibronectin, laminin, and transforming growth factor-
(TGF-) in the grafts. Estradiol treatment resulted in an improved graft function, reduced glomerular sclerosis, and a diminished cellular infiltration, in parallel to a reduced ICAM-1, fibronectin, laminin, and TGF- expression. In animals treated with vehicle, the gender of the donor influenced the outcome. Grafts of male origin had good graft function and histology, whereas grafts from female donors developed severe proteinuria and glomerular, interstitial, and vascular damage.
Conclusions
These results suggest that a protective effect of estradiol on the progression of chronic rejection exists that is independent of donor gender. Additionally, a male kidney may benefit from the absence of testosterone, whereas the function of a female kidney deteriorates in the absence of estradiol.
Keywords:
chronic rejection, hemodynamics, growth hormones, estradiol, testosterone, transplantation
