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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Diabetes Association 2012
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.
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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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