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NDT Advance Access published online on September 6, 2005
Nephrology Dialysis Transplantation, doi:10.1093/ndt/gfh964
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© The Author [2005]. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org
Received January 6, 2005
Accepted May 25, 2005

Original Articles

Addition of oleic acid to delipidated bovine serum albumin aggravates renal damage in experimental protein-overload nephrosis

Mirjan M. van Timmeren 1*, Stephan J. L. Bakker 2, Coen A. Stegeman 2, Rijk O. B. Gans 2, and Harry van Goor 1

1 Department of Pathology and Laboratory Medicine, University Medical Center Groningen, Groningen, The Netherlands
2 Department of Internal Medicine, University Medical Center Groningen, Groningen, The Netherlands

* To whom correspondence should be addressed.
Mirjan M. van Timmeren, E-mail: m.m.van.timmeren{at}path.umcg.nl



  Abstract

Background. Non-esterified fatty acids (NEFA) carried on albumin may have a causal role in the development of chronic proteinuria-induced nephropathy. To investigate whether NEFA aggravate renal structural damage, we studied the effects of NEFA addition to delipidated bovine serum albumin (BSA) in protein-overload nephropathy.

Methods. Three groups of Wistar rats received daily intraperitoneal injections (3 weeks) of either 1 g NEFA-free BSA (BSA-0), or NEFA-free BSA with three (BSA-3) or six (BSA-6) molecules oleic acid added per BSA molecule. An additional group received saline injections only (SAL). Renal damage was evaluated by immunohistochemistry and RT-PCR.

Results. Interstitial and glomerular alpha-smooth muscle actin ({alpha}-SMA, marker of myofibroblast transformation) expression were higher in BSA-3/6 than in saline-injected controls (P<0.001). Glomerular macrophage influx and desmin (marker of glomerular epithelial cell damage) expression were higher in all BSA-injected rats than SAL (P<0.001). Interstitial macrophage influx was elevated in BSA-0/3 (P<0.05) and BSA-6 (P<0.001) compared to SAL. Addition of six molecules of oleic acid to BSA revealed higher interstitial and glomerular {alpha}-SMA expression (P<0.001), increased interstitial macrophage numbers (P<0.001) and enhanced glomerular desmin expression (P<0.05) compared to BSA-0. RT-PCR revealed higher glomerular {alpha}-SMA mRNA expression in BSA-3/6 than SAL (P<0.001 and 0.05, respectively), interstitial {alpha}-SMA mRNA was elevated in BSA-6 (P<0.05). Interstitial TGF-{beta}1 mRNA expression was significantly higher in BSA-3 than SAL (P<0.05).

Conclusions. These data show that addition of oleic acid to NEFA-free BSA aggravates renal damage, suggesting a role for NEFA in the pathogenesis of proteinuric nephropathies.

Keywords: albuminuria; non-esterified fatty acids; oleic acid; protein-overload; proteinuric nephropathies.
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