11beta-hydroxysteroid dehydrogenase activity in proteinuric patients and the effect of angiotensin-II receptor blockade.
BACKGROUND
It has been suggested that an altered setpoint of the 11betaHSD-mediated cortisol to cortisone interconversion towards cortisol contributes to sodium retention in nephrotic syndrome patients. We studied the parameters of 11betaHSD 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 11betaHSD activity.


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 11betaHSD 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.
Kerstens
M N
MN
University Hospital Groningen, The Netherlands. m.n.kerstens@int.azg.nl
Buter
H
H
Navis
G J
GJ
Dullaart
R P F
RP
D042842:11-beta-Hydroxysteroid Dehydrogenases; D000328:Adult; D057911:Angiotensin Receptor Antagonists; D016022:Case-Control Studies; D003348:Cortisone / Q000097:blood / Q000652:urine; D003350:Cortodoxone / Q000031:analogs & derivatives* / Q000652:urine; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000097:blood / Q000652:urine; D006913:Hydroxysteroid Dehydrogenases / Q000378:metabolism*; D007668:Kidney / Q000201:enzymology*; D019808:Losartan / Q000627:therapeutic use*; D008297:Male; D011507:Proteinuria / Q000188:drug therapy* / Q000201:enzymology* / Q000378:metabolism; D013760:Tetrahydrocortisol / Q000652:urine; D013761:Tetrahydrocortisone / Q000652:urine
D057911:Angiotensin Receptor Antagonists; D013761:Tetrahydrocortisone; C009412:tetrahydro-11-deoxycortisol; D013760:Tetrahydrocortisol; D006913:Hydroxysteroid Dehydrogenases; D042842:11-beta-Hydroxysteroid Dehydrogenases; D019808:Losartan; D003348:Cortisone; D003350:Cortodoxone; D006854:Hydrocortisone