Proteinuria decreases tissue lipoprotein receptor levels resulting in altered lipoprotein structure and increasing lipid levels

Limin Wang, Gregory C. Shearer, Madhu S. Budamagunta, John C Voss, Alessio Molfino, George Kaysen

Research output: Contribution to journalArticle

14 Scopus citations


Rats with nephrotic syndrome (NS) have a fivefold increase in lipids and a similar decrease in triglyceride-rich lipoprotein (TRL) clearance. Lipoprotein lipase (LPL) is reduced both in NS and in the Nagase analbuminemic rat. These rats have nearly normal triglyceride levels and TRL clearance, suggesting that reduction in LPL alone is insufficient to cause increased TRL levels. Apolipoprotein E (apoE) was decreased in lipoprotein fractions in NS, but not in analbuminemia. Here we tested whether decreased apoE binding to lipoproteins in NS contributes to hyperlipidemia by decreasing their affinity for lipoprotein receptors. Plasma apoE was increased 60% in both NS and analbuminemia compared with control (CTRL) as a result of a 60% decreased apoE clearance. Very-low-density lipoprotein and high-density lipoprotein in NS had significantly less apoE per mole of phospholipid compared with analbuminemia or CTRL and significantly greater lipid content; however, apoE binding did not differ by lipoprotein class or group. There was a significant reduction of receptors for lipoproteins in nearly all tissues in NS compared with CTRL and analbuminemia. Thus, apoE within lipoprotein fractions was reduced by dilution resulting from expansion of the lipid fraction due to decreased lipolysis and not to differing affinity for apoE. Decreased lipoprotein receptors result from proteinuria and contribute to hyperlipidemia in NS.

Original languageEnglish (US)
Pages (from-to)990-999
Number of pages10
JournalKidney International
Issue number9
StatePublished - Nov 1 2012



  • apolipoprotein E
  • lipids
  • metabolism
  • proteinuria
  • VLDL

ASJC Scopus subject areas

  • Nephrology

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