HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 289/4/F880    most recent 00451.2004v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (7) Citing Articles via Google Scholar Google Scholar Articles by Nakhoul, F. Articles by Abassi, Z. Search for Related Content PubMed PubMed Citation Articles by Nakhoul, F. Articles by Abassi, Z.

Glomerular abundance of nephrin and podocin in experimental nephrotic syndrome: different effects of antiproteinuric therapies

¹Department of Nephrology, Rambam Medical Center, Haifa; and ²Department of Physiology and Biophysics, Rappaport Family Institute for Research in the Medical Sciences, Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel

Submitted 15 December 2004 ; accepted in final form 24 May 2005

Nephrotic syndrome (NS) is a clinical state characterized by massive proteinuria, hypoalbuminemia, and eventual edema formation. Although the mechanisms underlying this phenomenon are not yet fully clarified, it is well accepted that nephrin and podocin are involved in the development of proteinuria. The effects of early treatment with various antiproteinuric therapies on proteinuria and glomerular staining of nephrin and podocin in rats with experimental NS have not been previously studied. Proteinuria and glomerular nephrin and podocin immunofluorescence were examined in rat kidneys with adriamycin-induced NS and the effects of antiproteinuric drug therapies during 5 wk with enalapril, losartan, alone or in combination, omapatrilat, and mycophenolate mofetil on these parameters were assessed. Injection of adriamycin caused a significant increase in daily (from 21.8 ± 1.4 to 983.1 ± 45.8 mg/day, P < 0.01) and cumulative protein excretion (from negligible values to 22,490 ± 931 mg, P < 0.001) during 5 wk. Early treatment with enalapril significantly decreased the daily (641.7 ± 82.4 mg/day, P < 0.0023) and cumulative proteinuria (15,727 ± 2,204 mg, P < 0.001). A similar effect, although to a lesser extent, was obtained after omapatrilat treatment: cumulative proteinuria was reduced to 18,706 ± 1,042 mg, P < 0.001. In contrast, losartan treatment did not significantly influence the cumulative proteinuria that remained comparable (20,351 ± 1,360 mg, P > 0.05) to that observed in untreated NS rats. Unexpectedly, when losartan was given in combination with enalapril, it abolished the beneficial effects of the latter. Pretreatment with mycophenolate mofetil exerted a moderate antiproteinuric effect, which appeared only during the last week of the experimental treatment. Nephrotic rats exhibited severe disruption of slit diaphragm structure as seen by rapid and profound loss of nephrin and podocin. Beneficial effects of enalapril, omapatrilat, and mycophenolate mofetil paralleled the preservation of nephrin, as determined immunohistochemically, and enabled prediction of significant antiproteinuric responses. Enalapril alone or in combination with losartan resulted in significant preservation of podocin. Pretreatment with enalapril, and to a lesser extent omapatrilat, is superior to losartan in reducing proteinuria in NS rats. A combination of ACE inhibitors with ANG II receptor blockers does not provide any advantageous antiproteinuric therapy in these animals. Nephrin loss is an indication of proteinuria in NS and the antiproteinuric effects of ACE inhibitors, vasopeptidase inhibitors, and mycophenolate mofetil attenuate this reduction. Not all the drugs which restore podocin reduce urinary protein in NS.

adriamycin; proteinuria

This article has been cited by other articles:

				G. Wang, F. M.-M. Lai, K.-B. Lai, K.-M. Chow, B. C.-H. Kwan, P. K.-T. Li, and C.-C. Szeto Urinary messenger RNA expression of podocyte-associated molecules in patients with diabetic nephropathy treated by angiotensin-converting enzyme inhibitor and angiotensin receptor blocker Eur. J. Endocrinol., March 1, 2008; 158(3): 317 - 322. [Abstract] [Full Text] [PDF]

				F. Nakhoul, E. Khankin, A. Yaccob, H. Kawachi, T. Karram, H. Awaad, N. Nakhoul, A. Hoffman, and Z. Abassi Eplerenone potentiates the antiproteinuric effects of enalapril in experimental nephrotic syndrome Am J Physiol Renal Physiol, March 1, 2008; 294(3): F628 - F637. [Abstract] [Full Text] [PDF]

				Y. Xing, J. Ding, Q. Fan, and N. Guan Diversities of Podocyte Molecular Changes Induced by Different Antiproteinuria Drugs. Experimental Biology and Medicine, May 1, 2006; 231(5): 585 - 593. [Abstract] [Full Text] [PDF]