Apolipoprotein E in idiopathic nephrotic syndrome and focal segmental glomerulosclerosis

• Published in: Kidney international Vol. 63; no. 2; pp. 686 - 695
• Main Authors: Bruschi, Maurizio, Catarsi, Paolo, Candiano, Giovanni, Rastaldi, Maria Pia, Musante, Luca, Scolari, Francesco, Artero, Mary, Carraro, Michele, Carrea, Alba, Caridi, Gianluca, Zennaro, Cristina, Sanna-Cherchi, Simone, Viola, Fabio Battista, Ferrario, Franco, Perfumo, Francesco, Ghiggeri, Gian Marco
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.02.2003; Nature Publishing; Elsevier Limited
• Subjects: Adolescent; Adult; apoE genotype; Apolipoproteins E - blood; Apolipoproteins E - genetics; Apolipoproteins E - metabolism; Apolipoproteins E - urine; Biological and medical sciences; cell matrix; Child; Child, Preschool; cholesterol absorption; Cohort Studies; Female; Genotype; Glomerulonephritis; Glomerulosclerosis, Focal Segmental - blood; Glomerulosclerosis, Focal Segmental - genetics; Glomerulosclerosis, Focal Segmental - metabolism; Glomerulosclerosis, Focal Segmental - urine; Humans; hyperlipidemia; Kidney - metabolism; lipid metabolism; Male; Medical sciences; mesangial cell proliferation; Nephrology. Urinary tract diseases; Nephropathies. Renovascular diseases. Renal failure; Nephrotic Syndrome - blood; Nephrotic Syndrome - genetics; Nephrotic Syndrome - metabolism; Nephrotic Syndrome - urine; progressive renal disease; hyperlipidemia; apoE genotype; cell matrix; cholesterol absorption; progressive renal disease; lipid metabolism; mesangial cell proliferation; Glomerulonephritis; Kidney disease; Human; Urinary system disease; Pathogenesis; Idiopathic; Metabolic diseases; Genotype; Lipids; Nephrotic syndrome; Focal glomerulonephritis; Apolipoprotein E; Hyperlipemia; Dyslipemia
• ISSN: 0085-2538; 1523-1755
• DOI: 10.1046/j.1523-1755.2003.00777.x

Apolipoprotein E in idiopathic nephrotic syndrome and focal segmental glomerulosclerosis. 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. 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. The allelic frequencies of the three major haplotypes γ2, γ3, and γ4 were the same in nephrotic patients versus controls, and homozygosity for γ3γ3 was comparably the most frequent genotype (70 vs. 71%) followed by γ3γ4, γ2γ3, γ2γ4, γ4γ4. 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. 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.