Apolipoprotein e in idiopathic nephrotic syndrome and focal segmental glomerulosclerosis

Maurizio Bruschi, Paolo Catarsi, Giovanni Candiano, Maria Pia Rastaldi, Luca Musante, Francesco Scolari, Mary Artero, Michele Carraro, Alba Carrea, Gianluca Caridi, Cristina Zennaro, Simone Sanna-Cherchi, Fabio Battista Viola, Franco Ferrario, Francesco Perfumo, Gian Marco Ghiggeri

Research output: Contribution to journalArticlepeer-review

Abstract

Background. Hyperlipemia characterizes nephrotic syndrome (NS) and contributes to the progression of the underlying nephropathy. The data in the literature support an implication of apolipoprotein E (apoE) in both hyperlipemia and focal segmental glomerulosclerosis (FSGS), a malignant condition associated with NS. Methods. The apoE genotype was determined in 209 nephrotic patients, who were classified according to age and their response to steroids as resistant children (N = 96) and adults (43), and steroid dependent (33) and steroid responder (37) children. A total of 123 presented the histological features of FSGS. In a subgroup of 28 patients, serum and urinary levels of apoE and renal deposits were evaluated by immunofluorescence. Results. The allelic frequencies of the three major haplotypes ε2, ε3, and ε4 were the same in nephrotic patients versus controls, and homozygosity for ε3εe3 was comparably the most frequent genotype (70 vs. 71%) followed by ε3ε4, ε2ε3, ε2ε4, ε4ε4. Serum levels of apoE were fivefold higher in NS and in FSGS patients than in controls, with a direct correlation with hypercholesterolemia and proteinuria. ApoE genotypes did not influence serum levels. Urinary levels were 1/10,000 of serum with an increment in nephrotic urines. Finally, immunofluorescence demonstrated the absence of apoE in sclerotic glomeruli, while comparably nephrotic patients with membranous nephropathy had an increased glomerular expression of apoE. Conclusions. ApoE is dysregulated in NS with a marked increment in serum, which is a part of the complex lipid metabolism. Down-regulation of glomerular apoE instead is a peculiarity of FSGS and may contribute to the pathogenesis of the disease. The normal distribution of apoE genotypes in nephrotic patients with FSGS excludes a pathogenetic role of genetic variants.

Original languageEnglish
Pages (from-to)686-695
Number of pages10
JournalKidney International
Volume63
Issue number2
DOIs
Publication statusPublished - 2003

Keywords

  • ApoE genotype
  • Cell matrix
  • Cholesterol absorption
  • Hyperlipidemia
  • Lipid metabolism
  • Mesangial cell proliferation
  • Progressive renal disease

ASJC Scopus subject areas

  • Nephrology

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