Endocrine Abstracts (2003) 6 P69


M Quinkler1, D Zehnder2, J Lepenies2, S Hughes1, COS Savage2, M Hewison1 & PM Stewart1

1Division of Medical Sciences, University of Birmingham, Queen Elizabeth Hospital, Edgbaston, Birmingham, B15 2TH, UK; 2Department of Nephrology, University of Birmingham, Queen Elizabeth Hospital, Edgbaston, B15 2TH, UK.

The role of 11beta-HSD2 is to provide selective access of aldosterone to the mineralocorticoid receptor 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 expression in a large number of patients (n=102) undergoing kidney biopsy because of underlying renal disease. 11beta-HSD2 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.

11beta-HSD2 mRNA expression was significantly higher (p<0.01) in renal biopsies from female (n=47, mean-dCT 11.66 plus/minus SD 2.67) compared to males (n=55, dCT 13.32 plus/minus 2.95). 11beta-HSD2 expression did not correlate with blood pressure, or urinary Na/K ratio in the group as a whole but a marked positive correlation with creatinine clearance was observed (p=<0.01). No significant difference in 11beta-HSD2 expression was found between groups with no albuminuria (<30mg/24h, n=28, dCT 11.95 plus/minus 2.32), microalbuminuria (30-300mg/24h, n=31, dCT 12.71 plus/minus 3.01), moderate (300mg-2g/24h, n=18, dCT 12.41 plus/minus 2.35) and severe albuminuria (>2g/24h, n=15, dCT 12.73 plus/minus 3.72). Patients with hypertension (n=47; mean-arterial-pressure(MAP) 100.8 plus/minus 10.3mmHg, dCT 12.66 plus/minus 2.7) showed no significant difference in 11beta-HSD2 expression to patients without hypertension (n=55, MAP 90.3 plus/minus 12.0mmHg, dCT 12.21 plus/minus 2.88).

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.

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