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NDT Advance Access published online on January 12, 2006

Nephrology Dialysis Transplantation, doi:10.1093/ndt/gfk050
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© The Author [2006]. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org
Received October 12, 2004
Accepted December 13, 2005


Orginal Article

Beneficial effects of orosomucoid on the glomerular barrier in puromycin aminonucleoside-induced nephrosis

Clara Hjalmarsson 1 *, Martin E. Lidell 2, and Börje Haraldsson 1

1 Department of Nephrology, Sahlgrenska Academy, Göteborg University, Gothenburg, Sweden
2 Department of Medical Biochemistry, Göteborg University, Gothenburg, Sweden

* To whom correspondence should be addressed.
Clara Hjalmarsson, E-mail: Clara.Hjalmarsson{at}kidney.med.gu.se



  Abstract

Background. In a hitherto unconfirmed report, orosomucoid was reported to ameliorate the nephrotic syndrome induced by puromycin aminonucleoside (PAN) in rats.

Methods. We wanted to test this hypothesis and extend the analysis of the effects on the glomerular barrier. Glomerular filtration rate (GFR), and fractional clearance for albumin ({theta}albumin) and for neutral Ficolls were estimated in cooled isolated perfused kidneys. Modern transport equations were used to estimate glomerular size selectivity and charge selectivity. Also, podocyte morphology was studied. Four groups of rats (4x n = 8) were administered PAN intraperitoneally and treated daily for 5 days with orosomucoid in two different doses (groups A and B), albumin (group C) or saline (group D). Two additional groups of rats (2 x n = 8) were used as controls and these rats received either saline (group E) or orosomucoid (group F) but no PAN.

Results. Treatment with orosomucoid restored podocyte morphology and renal function from the damaging effects of PAN in a dose-dependent manner. GFR was significantly reduced by PAN (groups C and D) when compared with controls (groups E and F). This effect was partly (group A) or completely (group B) reversed by orosomucoid. The {theta}albumin was 0.002±0.001 (mean±SEM) in controls (group E) and was unaffected by orosomucoid per se (group F). PAN increased {theta}albumin to 0.020±0.001 in group C and to 0.021±0.001 in group D, while it was significantly less in group A, 0.014±0.001, P<0.05. The heterogeneous charged fibre model analysis revealed that PAN reduced the relative volume of negatively charged fibres, {phi} from 7.1±0.08% (group E) to 48% of this value in groups C and D (P<0.001); {phi} was 4.5±0.04% in group A, 5.3±0.44% in group B, and 6.1±0.11% in group F.

Conclusion. High doses of orosomucoid completely normalized the glomerular barrier in six out of eight animals with puromycin-induced nephrotic syndrome. Thus, orosomucoid has a promising therapeutic potential for certain kidney disorders.

Keywords: {alpha}1-acid glycoprotein; charged fibre; glomerular; nephrotic; permeability; size selectivity.
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[Abstract] [Full Text] [PDF]



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