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11b‐hydroxysteroid dehydrogenase activity in proteinuric patients and the effect of angiotensin‐II receptor blockade
Author(s) -
Kerstens M. N.,
Buter H.,
Navis G. J.,
Dullaart R. P. F.
Publication year - 2002
Publication title -
european journal of clinical investigation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.164
H-Index - 107
eISSN - 1365-2362
pISSN - 0014-2972
DOI - 10.1046/j.1365-2362.2002.01013.x
Subject(s) - endocrinology , medicine , cortisone , losartan , chemistry , 11β hydroxysteroid dehydrogenase type 1 , urinary system , natriuresis , excretion , angiotensin ii , blood pressure , dehydrogenase , enzyme , biochemistry
Background It has been suggested that an altered setpoint of the 11βHSD‐mediated cortisol to cortisone interconversion towards cortisol contributes to sodium retention in nephrotic syndrome patients. We studied the parameters of 11βHSD activity in proteinuric patients, in particular its activity at the kidney level. We also studied the effect of angiotensin‐II receptor blockade on the parameters of 11βHSD activity. Materials and methods Serum cortisol/cortisone ratio and the urinary ratios of (tetrahydrocortisol + allo‐tetrahydrocortisol)/tetrahydrocortisone [(THF + allo‐THF)/THE] and of urinary free cortisol/free cortisone (UFF/UFE) were measured in eight proteinuric patients and compared with eight matched, healthy subjects. Patients were subsequently studied after 4 weeks’ treatment with losartan 50 mg day −1 and placebo, respectively. Results No significant differences between the proteinuric patients and the healthy subjects were observed in the serum cortisol, serum cortisone, serum cortisol to cortisone ratio, or in the urinary excretions of THF, allo‐THF, THE, sum of cortisol metabolites, or the (THF + allo‐THF)/THE ratio. Urinary free cortisol excretion and the UFF/UFE ratio were lower in the proteinuric patients than in the healthy subjects (56 ± 21 vs. 85 ± 24 pmol min −1 , P < 0·05, and 0·39 ± 0·07 vs. 0·63 ± 0·28, P < 0·05, respectively). Mean arterial pressure and proteinuria were reduced significantly during losartan treatment, but without concomitant changes in peripheral cortisol metabolism. Conclusions Increased renal inactivation of cortisol in proteinuric patients does not support the contention that altered 11βHSD activity contributes to sodium retention in patients with nephrotic syndrome. Losartan 50 mg d.d. reduces mean arterial pressure and proteinuria, but does not exert a significant effect on the cortisol to cortisone interconversion.