Nephrol Dial Transplant (2002) 17: 753-758
© 2002 European Renal Association-European Dialysis and Transplant Association
Reduced 11ß-hydroxysteroid dehydrogenase activity in experimental nephrotic syndrome
Division of Nephrology and Hypertension, University Hospital of Berne, Inselspital, Berne, Switzerland
Background. The disease state of the nephrotic syndrome is characterized by abnormal renal sodium retention that cannot be completely explained by a secondary hyperaldosteronism for the following reasons. Firstly, in rats an enhanced sodium retention is observed before proteinuria with intravascular volume depletion occurs. Secondly, in patients with the nephrotic syndrome, volume expansion with hypertension has been reported despite suppression of the renin-aldosterone system. Therefore, another mechanism for sodium retention must be postulated for this disease state. We hypothesize that this mechanism is a reduced 11ß-hydroxysteroid dehydrogenase 2 (11ß-HSD2) activity, a phenomenon known to cause enhanced access of cortisol or corticosterone to the mineralocorticoid receptor.
Methods. We assessed the 11ß-HSD activity by measuring the urinary ratio of tetrahydrocorticosterone (THB) plus 5
-tetrahydrocorticosterone (5-THB) to 11-dehydro-tetrahydrocorticosterone (THA) by gas chromatography–mass spectrometry in rats with puromycin aminonucleoside (PAN)-induced proteinuria and with adriamycin nephrosis. Furthermore, the plasma ratios of corticosterone to 11-dehydrocorticosterone were measured.
Results. The urinary ratio of (THB+5-THB)/THA increased in all animals following injection of PAN or adriamycin, indicating a reduced activity of 11ß-HSD. The reduced activity of 11ß-HSD was confirmed by an increased plasma ratio of corticosterone to 11-dehydrocorticosterone. The changes in the glucocorticoid metabolite ratios were already present before significant proteinuria appeared.
Conclusion. PAN- or adriamycin-treated rats develop proteinuria with a reduced activity of 11ß-HSD, a mechanism contributing to the abnormal sodium retention in nephrotic syndrome.
Keywords: adriamycin; gas chromatography–mass spectrometry; 11ß-hydroxysteroid dehydrogenase; nephrotic syndrome; proteinuria; puromycin aminonucleoside; sodium retention
Correspondence and offprint requests to: Bruno Vogt, MD, Division of Nephrology and Hypertension, Inselspital, Freiburgstrasse 15, CH-3010 Berne, Switzerland. Email: bvogt{at}insel.ch
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  S. W. Kim, S. de Seigneux, M. C. Sassen, J. Lee, J. Kim, M. A. Knepper, J. Frokiaer, and S. Nielsen Increased apical targeting of renal ENaC subunits and decreased expression of 11betaHSD2 in HgCl2-induced nephrotic syndrome in rats Am J Physiol Renal Physiol, March 1, 2006; 290(3): F674 - F687. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Quinkler, D. Zehnder, J. Lepenies, M. D Petrelli, J. S Moore, S. V Hughes, P. Cockwell, M. Hewison, and P. M Stewart Expression of renal 11{beta}-hydroxysteroid dehydrogenase type 2 is decreased in patients with impaired renal function Eur. J. Endocrinol., August 1, 2005; 153(2): 291 - 299. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Yao, R. C. Harris, and M.-Z. Zhang Interactions between 11{beta}-hydroxysteroid dehydrogenase and COX-2 in kidney Am J Physiol Regulatory Integrative Comp Physiol, June 1, 2005; 288(6): R1767 - R1773. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. N. Kerstens, G. Navis, and R. P. F. Dullaart Does a reduced 11{beta}HSD type 2 activity contribute to sodium retention in the nephrotic syndrome? Nephrol. Dial. Transplant., March 1, 2003; 18(3): 620 - 620. [Full Text] [PDF]
|
|