Significance of urinary full-length and ectodomain forms of megalin in patients with type 2 diabetes.
Significance of urinary full-length and ectodomain forms of megalin in patients with type 2 diabetes.
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DOI：
10.2337/dc11-1684
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发表时间：
2012-05
期刊：
影响因子：
16.2
通讯作者：
Saito A
中科院分区：
文献类型：
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作者：
Ogasawara S;Hosojima M;Kaseda R;Kabasawa H;Yamamoto-Kabasawa K;Kurosawa H;Sato H;Iino N;Takeda T;Suzuki Y;Narita I;Yamagata K;Tomino Y;Gejyo F;Hirayama Y;Sekine S;Saito A
Megalin是近曲小管细胞的内吞受体，参与糖尿病肾病（DN）蛋白尿的发生。为了开发与DN发病机制相关的有效的新生物标志物，我们研究了2型糖尿病患者尿巨蛋白排泄。应用抗megalin氨基端（amino [A]-megalin assay）和羧基端（C-megalin assay）的单克隆抗体，建立了megalin的双抗体夹心酶联免疫吸附试验（ELISA）系统，对68例2型糖尿病患者尿液中megalin进行检测。A-巨蛋白测定主要在可溶性尿组分中检测到巨蛋白胞外域形式，而C-巨蛋白测定在可溶性和不溶性组分中鉴定出全长形式。正常白蛋白尿患者的尿C-巨蛋白水平显著升高，与白蛋白尿增加一致，并且与估计肾小球滤过率（eGFR）（<60 mL/min/1.73 m2）的相关性优于尿白蛋白。与此相反，正常和微量白蛋白尿患者的尿A-巨蛋白水平升高，而大量白蛋白尿患者的尿A-巨蛋白水平未升高。尿C-巨蛋白水平也与血浆无机磷酸盐呈正相关，而在没有出血特征且未服用维生素D类似物、磷酸盐结合剂或红细胞生成刺激剂的患者中，与血红蛋白水平呈负相关。通过C-巨蛋白测定测量的尿全长巨蛋白排泄与eGFR降低密切相关，并与DN的严重程度、磷酸盐失调和贫血相关，而通过A-巨蛋白测定测量的巨蛋白胞外域的尿排泄可能与2型糖尿病早期DN的独特机制相关。
Megalin, an endocytic receptor in proximal tubule cells, is involved in the mechanisms of albuminuria in diabetic nephropathy (DN). To develop efficient novel biomarkers associated with the pathogenesis of DN, we investigated urinary megalin excretion in type 2 diabetes. Sandwich enzyme-linked immunosorbent assay systems were established with monoclonal antibodies against the NH2 (amino [A]-megalin assay) and COOH (C-megalin assay) termini of megalin to analyze urinary forms of megalin in 68 patients with type 2 diabetes. The A-megalin assay mainly detected a megalin ectodomain form in the soluble urinary fraction, whereas the C-megalin assay identified a full-length form in both soluble and insoluble fractions. Urinary C-megalin levels were significantly high in patients with normoalbuminuria, were elevated in line with increased albuminuria, and showed a better association with estimated glomerular filtration rate (eGFR) (<60 mL/min/1.73 m2) than did urinary albumin. In contrast, urinary A-megalin levels were increased in patients with normo- and microalbuminuria but not in those with macroalbuminuria. Urinary C-megalin levels were also positively associated with plasma inorganic phosphate and negatively with hemoglobin levels in those showing no features of bleeding and not taking vitamin D analogs, phosphate binders, or erythropoiesis-stimulating agents. Urinary full-length megalin excretion as measured by the C-megalin assay is well associated with reduced eGFR and linked to the severity of DN, phosphate dysregulation, and anemia, whereas urinary excretion of megalin ectodomain as measured by the A-megalin assay may be associated with distinctive mechanisms of earlier DN in type 2 diabetes.
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影响因子：
--
作者：
Saito A;Sato H;Iino N;Takeda T
通讯作者：
Takeda T
影响因子：
168.9
作者：
Matsushita, Kunihiro;van der Velde, Marije;Astor, Brad C.;Woodward, Mark;Levey, Andrew S.;de Jong, Paul E.;Coresh, Josef;Gansevoort, Ron T.
通讯作者：
Gansevoort, Ron T.
影响因子：
13.6
作者：
Kestenbaum, B;Sampson, JN;Andress, DL
通讯作者：
Andress, DL
DOI：
10.1073/pnas.91.21.9725
发表时间：
1994-10-11
影响因子：
11.1
作者：
SAITO, A;PIETROMONACO, S;FARQUHAR, MG
通讯作者：
FARQUHAR, MG
影响因子：
120.7
作者：
Kramer, HJ;Nguyen, QD;Hsu, CY
通讯作者：
Hsu, CY