Lipoprotein(a) in the nephrotic syndrome: Molecular analysis of lipoprotein(a) and apolipoprotein(a) fragments in plasma and urine
Lipoprotein(a) in the nephrotic syndrome: Molecular analysis of lipoprotein(a) and apolipoprotein(a) fragments in plasma and urine
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DOI：
10.1681/asn.v113507
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发表时间：
2000-03-01
影响因子：
13.6
通讯作者：
Thillet, J
中科院分区：
文献类型：
--
作者：
Doucet, C;Mooser, V;Thillet, J
脂蛋白（a）（Lp（a））是一种致动脉粥样硬化颗粒，其血浆水平在肾脏疾病中升高，这表明该器官在Lp（a）代谢中的作用。循环中载脂蛋白（a）（apo（a））的N-末端片段通过肾脏途径进行加工和消除，这一事实提供了肾脏在Lp（a）清除中发挥作用的其他证据。为了进一步了解这种肾脏排泄的机制，在肾病综合征患者（n = 15）中测定了血浆和尿液中apo（a）片段相对于血浆Lp（a）水平的水平。在血浆中，（24.7 +/- 20.4 vs. 2.16 +/- 2.99 μ g/ml，P < 0.0001）以及载脂蛋白（a）片段的相对量（总Lp（a）的4.6 ± 3.4%对2.1 ± 3.3%，P < 0.0001）在肾病患者中显著高于对照组，正常血脂人群。此外，肾病综合征患者尿apo（a）排泄量显著高于对照组（578 ± 622 ng/ml/mg肌酐对27.7 ± 44 ng/ml/mg肌酐，P < 0.001）。然而，两组apo（a）片段的分解率相似（肾病和对照受试者分别为0.68 +/- 0.67%和0.62 +/- 0.47%），表明肾病受试者apo（a）片段的血浆浓度增加更多地依赖于合成率而不是分解率。对尿中apo（a）免疫反应物质的分子分析表明，肾病患者的apo（a）片段模式与对照组不同。在肾病患者的尿液中检测到全长apo（a）、与血浆中存在的apo（a）大小相似的大N端apo（a）片段以及apo（a）的C端片段，但在对照组的尿液中未检测到。所有这些apo（a）形式都是除了正常尿液中存在的较小N-末端apo（a）片段之外的。本研究还证实了肾病患者尿中存在Lp（a）。这些数据表明，在肾病综合征中，Lp（a）和大片段的apo（a）被肾脏通过肾小球被动过滤，而较小的apo（a）片段被分泌到尿液中。
Plasma levels of lipoprotein(a) (Lp(a)), an atherogenic particle, are elevated in kidney disease, which suggests a role of this organ in the metabolism of Lp(a). Additional evidence for a role of the kidney in the clearance of Lp(a) is provided by the fact that circulating N-terminal fragments of apolipoprotein(a) (apo(a)) are processed and eliminated by the renal route. To further understand the mechanism underlying such renal excretion, the levels of apo(a) fragments in plasma and urine relative to plasma Lp(a) levels were determined in patients with nephrotic syndrome (n = 15). In plasma, the absolute (24.7 +/- 20.4 versus 2.16 +/- 2.99 mu g/ml, P < 0.0001) as well as the relative amounts of apo(a) fragments (4.6 +/- 3.4% versus 2.1 +/- 3.3% of total Lp(a), P < 0.0001) were significantly elevated in nephrotic patients compared with a control, normolipidemic population. In addition, urinary apo(a) excretion in patients with nephrotic syndrome was markedly elevated compared with that in control subjects (578 +/- 622 versus 27.7 +/- 44 ng/ml per mg creatinine, P < 0.001). However, the fractional catabolic rates of apo(a) fragments were similar in both groups (0.68 +/- 0.67% and 0.62 +/- 0.47% in nephrotic and control subjects, respectively), suggesting that increased plasma concentrations of apo(a) fragments in nephrotic subjects are more dependent on the rate of synthesis rather than on the catabolic rate. Molecular analysis of apo(a) immunoreactive material in urine revealed that the patterns of apo(a) fragments in nephrotic patients were distinct from those of control subjects. Full-length apo(a), large N-terminal apo(a) fragments similar in size to those present in plasma, as well as C-terminal fragments of apo(a) were detected in urine from nephrotic patients but not in urine from controls. All of these apo(a) forms were in addition to smaller N-terminal apo(a) fragments present in normal urine. This study also demonstrated the presence of Lp(a) in urine from nephrotic patients by ultracentrifugal fractionation. These data suggest that in nephrotic syndrome, Lp(a) and large fragments of apo(a) are passively filtered by the kidney through the glomerulus, whereas smaller apo(a) fragments are secreted into the urine.