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
Laboratory of Pathophysiology of Uremia and Unit of Nephrology, G. Gaslini Children's Hospital, Genoa, Italy.
Kidney Int. 2003 Feb;63(2):686-95. doi: 10.1046/j.1523-1755.2003.00777.x.
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 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.
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.
高脂血症是肾病综合征（NS）的特征之一，并促使潜在肾病进展。文献数据支持载脂蛋白E（apoE）与高脂血症以及局灶节段性肾小球硬化（FSGS）（一种与NS相关的恶性病症）均有关联。
对209例肾病患者进行apoE基因分型，这些患者根据年龄以及对类固醇的反应分为耐药儿童（N = 96）和成人（43例），以及类固醇依赖型（33例）和类固醇反应型（37例）儿童。共有123例呈现FSGS的组织学特征。在一个28例患者的亚组中，通过免疫荧光评估apoE的血清和尿液水平以及肾脏沉积物。
肾病患者与对照组中三种主要单倍型ε2、ε3和ε4的等位基因频率相同，ε3ε3纯合子是最常见的基因型（分别为70%和71%），其次是ε3ε4、ε2ε3、ε2ε4、ε4ε4。NS和FSGS患者的apoE血清水平比对照组高五倍，与高胆固醇血症和蛋白尿直接相关。apoE基因型不影响血清水平。尿液水平是血清的万分之一，肾病患者尿液中有所增加。最后，免疫荧光显示硬化肾小球中不存在apoE，而患有膜性肾病的肾病患者肾小球中apoE表达增加。
NS中apoE调节异常，血清中显著增加，这是复杂脂质代谢的一部分。肾小球apoE的下调是FSGS的一个特点，可能有助于疾病的发病机制。FSGS肾病患者中apoE基因型的正常分布排除了基因变异的致病作用。
