title: Apolipoprotein E in idiopathic nephrotic syndrome and focal segmental glomerulosclerosis.
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 epsilon2, epsilon3, and epsilon4 were the same in nephrotic patients versus controls, and homozygosity for epsilon3epsilon3 was comparably the most frequent genotype (70 vs. 71%) followed by epsilon3epsilon4, epsilon2epsilon3, epsilon2epsilon4, epsilon4epsilon4. 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.
authors.affiliation: Laboratory of Pathophysiology of Uremia and Unit of Nephrology, G. Gaslini Children's Hospital, Genoa, Italy.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Bruschi
authors.forename: Paolo
authors.initials: P
authors.lastname: Catarsi
authors.forename: Giovanni
authors.initials: G
authors.lastname: Candiano
authors.forename: Maria Pia
authors.initials: MP
authors.lastname: Rastaldi
authors.forename: Luca
authors.initials: L
authors.lastname: Musante
authors.forename: Francesco
authors.initials: F
authors.lastname: Scolari
authors.forename: Mary
authors.initials: M
authors.lastname: Artero
authors.forename: Michele
authors.initials: M
authors.lastname: Carraro
authors.forename: Alba
authors.initials: A
authors.lastname: Carrea
authors.forename: Gianluca
authors.initials: G
authors.lastname: Caridi
authors.forename: Cristina
authors.initials: C
authors.lastname: Zennaro
authors.forename: Simone
authors.initials: S
authors.lastname: Sanna-Cherchi
authors.forename: Fabio Battista
authors.initials: FB
authors.lastname: Viola
authors.forename: Franco
authors.initials: F
authors.lastname: Ferrario
authors.forename: Francesco
authors.initials: F
authors.lastname: Perfumo
authors.forename: Gian Marco
authors.initials: GM
authors.lastname: Ghiggeri
mesh_terms: D000293:Adolescent; D000328:Adult; D001057:Apolipoproteins E / Q000097:blood / Q000235:genetics / Q000378:metabolism* / Q000652:urine; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D005260:Female; D005838:Genotype; D005923:Glomerulosclerosis, Focal Segmental / Q000097:blood / Q000235:genetics / Q000378:metabolism* / Q000652:urine; D006801:Humans; D007668:Kidney / Q000378:metabolism; D008297:Male; D009404:Nephrotic Syndrome / Q000097:blood / Q000235:genetics / Q000378:metabolism* / Q000652:urine
chemical_list: D001057:Apolipoproteins E