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Endocrine Abstracts (2004) 7 P55

BES2004 Poster Presentations Diabetes, metabolism and cardiovascular (43 abstracts)

Expression of mineralocorticoid effector mechanisms in renal biopsies of patients with severe proteinuria

M Quinkler 1 , D Zehnder 2 , J Lepenies 2 , S Hughes 1 , GW Lipkin 2 , M Hewison 1 & PM Stewart 1


1Department of Medicine, Queen Elizabeth Hospital, University of Birmingham, Birmingham, UK; 2Department of Nephrology, Queen Elizabeth Hospital, Birmingham, UK.


The role of 11beta-HSD2 is to provide selective access of aldosterone to the mineralocorticoid receptor (MR) by inactivating cortisol. Evidence suggests impaired 11beta-HSD2 activity in some patients with hypertension but also in patients with renal disease where it may contribute to sodium retention, oedema and hypertension. To date these studies have relied upon urinary cortisol metabolite analyses as markers of renal 11beta-HSD2 activity. We have directly analysed renal 11beta-HSD2, MR and sgk1 expression in a large number of patients (n=102) undergoing kidney biopsy because of underlying renal disease. 11beta-HSD2, MR and sgk1 mRNA levels were quantified using TaqMan real-time PCR with 18S as housekeeping gene. Serum and 24h-urine samples were used to document underlying renal function and endocrine parameters. Expression of 11beta-HSD2, MR and sgk1 mRNA was significantly higher (p<0.05) in renal biopsies from female (n=47) compared to males (n=55). 11beta-HSD2, MR and sgk1 expression did not correlate with blood pressure or urinary Na/K ratio, but a marked positive correlation of 11beta-HSD2 expression with creatinine clearance was observed (p<0.01). No difference in 11beta-HSD2 expression was found between groups with no albuminuria (<30mg/24h, n=28), microalbuminuria (30-300mg/24h, n=31), moderate (300mg-2g/24h, n=18) and severe albuminuria (>2g/24h, n=15). However, we found a 5-fold increase in MR expression in patients with severe albuminuria, and a 2.5-fold increase in sgk1 expression in those with moderate and severe albuminuria. For the first time we have documented reduced kidney 11beta-HSD2 expression in patients with renal disease. Our data suggests that this is not influenced by underlying proteinuria or a diagnosis of hypertension but is directly correlated with creatinine clearance. Impaired 11beta-HSD2 expression may contribute to the increased sodium retention seen in patients with impaired renal function. In patients with severe proteinuria, the MR and sgk1 expression are significantly upregulated, suggesting a direct receptor-mediated activation of mineralocorticoid action.

Volume 7

23rd Joint Meeting of the British Endocrine Societies with the European Federation of Endocrine Societies

British Endocrine Societies 

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