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Significance of Urinary Full-Length and Ectodomain Forms of Megalin in Patients With Type 2 Diabetes
OBJECTIVE: 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. RESEARCH DESIGN A...
Autores principales: | , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Diabetes Association
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3329833/ https://www.ncbi.nlm.nih.gov/pubmed/22410816 http://dx.doi.org/10.2337/dc11-1684 |
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author | Ogasawara, Shinya Hosojima, Michihiro Kaseda, Ryohei Kabasawa, Hideyuki Yamamoto-Kabasawa, Keiko Kurosawa, Hiroyuki Sato, Hiroyoshi Iino, Noriaki Takeda, Tetsuro Suzuki, Yoshiki Narita, Ichiei Yamagata, Kunihiro Tomino, Yasuhiko Gejyo, Fumitake Hirayama, Yoshiaki Sekine, Sakari Saito, Akihiko |
author_facet | Ogasawara, Shinya Hosojima, Michihiro Kaseda, Ryohei Kabasawa, Hideyuki Yamamoto-Kabasawa, Keiko Kurosawa, Hiroyuki Sato, Hiroyoshi Iino, Noriaki Takeda, Tetsuro Suzuki, Yoshiki Narita, Ichiei Yamagata, Kunihiro Tomino, Yasuhiko Gejyo, Fumitake Hirayama, Yoshiaki Sekine, Sakari Saito, Akihiko |
author_sort | Ogasawara, Shinya |
collection | PubMed |
description | OBJECTIVE: 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. RESEARCH DESIGN AND METHODS: Sandwich enzyme-linked immunosorbent assay systems were established with monoclonal antibodies against the NH(2) (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. RESULTS: 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 m(2)) 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. CONCLUSIONS: 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. |
format | Online Article Text |
id | pubmed-3329833 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | American Diabetes Association |
record_format | MEDLINE/PubMed |
spelling | pubmed-33298332013-05-01 Significance of Urinary Full-Length and Ectodomain Forms of Megalin in Patients With Type 2 Diabetes Ogasawara, Shinya Hosojima, Michihiro Kaseda, Ryohei Kabasawa, Hideyuki Yamamoto-Kabasawa, Keiko Kurosawa, Hiroyuki Sato, Hiroyoshi Iino, Noriaki Takeda, Tetsuro Suzuki, Yoshiki Narita, Ichiei Yamagata, Kunihiro Tomino, Yasuhiko Gejyo, Fumitake Hirayama, Yoshiaki Sekine, Sakari Saito, Akihiko Diabetes Care Original Research OBJECTIVE: 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. RESEARCH DESIGN AND METHODS: Sandwich enzyme-linked immunosorbent assay systems were established with monoclonal antibodies against the NH(2) (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. RESULTS: 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 m(2)) 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. CONCLUSIONS: 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. American Diabetes Association 2012-05 2012-04-11 /pmc/articles/PMC3329833/ /pubmed/22410816 http://dx.doi.org/10.2337/dc11-1684 Text en © 2012 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details. |
spellingShingle | Original Research Ogasawara, Shinya Hosojima, Michihiro Kaseda, Ryohei Kabasawa, Hideyuki Yamamoto-Kabasawa, Keiko Kurosawa, Hiroyuki Sato, Hiroyoshi Iino, Noriaki Takeda, Tetsuro Suzuki, Yoshiki Narita, Ichiei Yamagata, Kunihiro Tomino, Yasuhiko Gejyo, Fumitake Hirayama, Yoshiaki Sekine, Sakari Saito, Akihiko Significance of Urinary Full-Length and Ectodomain Forms of Megalin in Patients With Type 2 Diabetes |
title | Significance of Urinary Full-Length and Ectodomain Forms of Megalin in Patients With Type 2 Diabetes |
title_full | Significance of Urinary Full-Length and Ectodomain Forms of Megalin in Patients With Type 2 Diabetes |
title_fullStr | Significance of Urinary Full-Length and Ectodomain Forms of Megalin in Patients With Type 2 Diabetes |
title_full_unstemmed | Significance of Urinary Full-Length and Ectodomain Forms of Megalin in Patients With Type 2 Diabetes |
title_short | Significance of Urinary Full-Length and Ectodomain Forms of Megalin in Patients With Type 2 Diabetes |
title_sort | significance of urinary full-length and ectodomain forms of megalin in patients with type 2 diabetes |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3329833/ https://www.ncbi.nlm.nih.gov/pubmed/22410816 http://dx.doi.org/10.2337/dc11-1684 |
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