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

Nephrol Dial Transplant. 2005 Nov;20(11):2349-57. doi: 10.1093/ndt/gfh964. Epub 2005 Sep 6.


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-beta1 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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / genetics
  • Actins / metabolism*
  • Animals
  • Biomarkers / metabolism
  • Disease Models, Animal
  • Gene Expression
  • Immunohistochemistry
  • Kidney Glomerulus / metabolism
  • Kidney Glomerulus / pathology
  • Male
  • Nephrosis / chemically induced
  • Nephrosis / metabolism*
  • Nephrosis / pathology
  • Oleic Acid / toxicity*
  • RNA, Messenger / genetics
  • Rats
  • Rats, Wistar
  • Reverse Transcriptase Polymerase Chain Reaction
  • Serum Albumin, Bovine / toxicity*
  • Transforming Growth Factor beta / genetics
  • Transforming Growth Factor beta / metabolism


  • Actins
  • Biomarkers
  • RNA, Messenger
  • Transforming Growth Factor beta
  • smooth muscle actin, rat
  • Serum Albumin, Bovine
  • Oleic Acid