Expression of renal 11beta-hydroxysteroid dehydrogenase type 2 is decreased in patients with impaired renal function.

Objective: Renal 11 beta-hydroxysteroid dehydrogenase type 2 (11 beta-HSD2) enables selective access of aldosterone to the mineralocorticoid receptor (MR). Impaired 11 beta-HSD2 activity has been suggested in patients with hypertension as well as in patients with renal disease, where it may contribute to sodium retention, oedema and hypertension. To date, these studies have relied upon urinary cortisol (F) metabolite levels as surrogate markers of renal 11 beta-HSU2 activity. Methods: We have directly analysed renal 11 beta-HSD2 mRNA expression in 95 patients undergoing kidney biopsy using TaqMan real-time PCR. Serum and 24-h urine samples were used to document underlying renal function and endocrine parameters. Urinary F and cortisone (E) metabolites were analysed using gas chromatography/mass spectrometry. Results: Expression of 11 beta-HSD2 did not correlate with blood pressure or urinary Na/K ratio, but a significant positive correlation with creatinine clearance was observed (r = 0.284; P < 0.01). Immunofluorescence and confocal laser microscopy confirmed decreased 11 beta-HSD2 expression in patients with impaired renal function. For the first time, we showed that 11 beta-HSD2 mRNA expression correlated negatively with the urinary free (UF) F/E (UFF/UFE) ratio (r = 0.276; P < 0.05) as well as with the urinary tetrahydrocortisol + 5 alpha-tetrahydrocortisol/tetrahydrocortisone ((THF + alpha THF)/THE) ratio (r = 0.256; P < 0.05). No difference in 11 beta-HSD2 mRNA expression or in the UFF/UFE ratio was found between groups with no proteinuria, microalbummuria, moderate or severe proteinuria. In contrast, the urinary (THF + alpha THF)/THE ratio increased significantly (P < 0.05) in patients with severe albuminuria, suggesting increased hepatic 11 beta-HSD1 in those patients. Conclusions: These data suggest that renal 11 beta-HSD2 expression may be represented only marginally better, if at all, by the UFF/UFE than by the (THF + alpha THF)/THE ratio. Reduced renal 11 beta-HSD2 expression may lead to occupancy of the MR by glucocorticoids such as cortisol and may contribute to the increased sodium retention seen in patients with impaired renal function.