Apolipoprotein E in idiopathic nephrotic syndrome and focal segmental glomerulosclerosis.
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.
Bruschi
Maurizio
M
Laboratory of Pathophysiology of Uremia and Unit of Nephrology, G. Gaslini Children's Hospital, Genoa, Italy.
Catarsi
Paolo
P
Candiano
Giovanni
G
Rastaldi
Maria Pia
MP
Musante
Luca
L
Scolari
Francesco
F
Artero
Mary
M
Carraro
Michele
M
Carrea
Alba
A
Caridi
Gianluca
G
Zennaro
Cristina
C
Sanna-Cherchi
Simone
S
Viola
Fabio Battista
FB
Ferrario
Franco
F
Perfumo
Francesco
F
Ghiggeri
Gian Marco
GM
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
D001057:Apolipoproteins E