DIMINISHED LEVELS OF DEHYDROEPIANDROSTERONE-SULFATE IN LONG-TERM RENAL TRANSPLANT PATIENTS ARE ASSOCIATED WITH POORER GRAFT FUNCTION

Abstract

21 The adrenocortical hormone Dehydroepiandrosterone (DHEA) represents not only a precursor for sex steroids but mediates also anabolic, antiglucocorticoid, antidepressive and immunoregulatory effects. Recently, Wiesniewski et al. reported on a correlation between DHEA-S serum levels and CD4 T-cell counts in HIV-infected patients. There was an inverse relation between disease progression and DHEA-S levels. Therefore, we were interested in the regulation of DHEA-S serum levels in long-term transplant patients. We speculated that low DHEA-S levels may be associated with a strong immunocompromised situation and, as a result of this, with a good graft function. DHEA-S levels were determined in the plasma of 89 renal and 8 renal/pancreas long-term transplant patients (mean: 59 months post Tx) by a commercially available immunoassay (DPC-Immulite). Additionally, plasma cortisol, ACTH and surface expression of T-cell activation markers on peripheral blood lymphocytes were investigated in a subgroup of 18 patients. Beside the known influence of age and sex we have found diminished DHEA-S levels in nearly all patients with a mean of 1.60 µmol/l (normal range: 0.95-15.6) which was correlated with the time post-Tx (r= -0.23, p<0.05). To exclude the influence of age and sex we have transformed absolute DHEA-S levels to percent of the expected value. In contrast to our hypothesis, there was a statistically significant negative correlation between DHEA-S levels and both serum creatinine (r= -0.34, p<0.01) and urea (r= -0.32, p<0.01) levels. Interestingly, we could not see any relation between levels of DHEA-S and plasma ACTH/cortisol which were normal in the majority of patients. Furthermore, there was no relation between flowcytometric signs of T-cell activation (high expression of CD25, CD71, HLA-DR) and DHEA-S levels. Our results indicate that diminished levels of DHEA-S in long-term renal transplant patients are not due to adrenocortical insufficiency. The association between low DHEA-S levels and poor graft function may result from chronic (intragraft) inflammation-induced or stress-induced downregulation of DHEA-S secretion. However, the pathophysiological relevance of diminished DHEA-S levels for long-term outcome remains unknown.