title: Significance of urinary full-length and ectodomain forms of megalin in patients with type 2 diabetes.
abstract: 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.
  
  
  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.
authors.affiliation: Division of Clinical Nephrology and Rheumatology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
authors.forename: Shinya
authors.initials: S
authors.lastname: Ogasawara
authors.forename: Michihiro
authors.initials: M
authors.lastname: Hosojima
authors.forename: Ryohei
authors.initials: R
authors.lastname: Kaseda
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Kabasawa
authors.forename: Keiko
authors.initials: K
authors.lastname: Yamamoto-Kabasawa
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kurosawa
authors.forename: Hiroyoshi
authors.initials: H
authors.lastname: Sato
authors.forename: Noriaki
authors.initials: N
authors.lastname: Iino
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Takeda
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Suzuki
authors.forename: Ichiei
authors.initials: I
authors.lastname: Narita
authors.forename: Kunihiro
authors.initials: K
authors.lastname: Yamagata
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Tomino
authors.forename: Fumitake
authors.initials: F
authors.lastname: Gejyo
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Hirayama
authors.forename: Sakari
authors.initials: S
authors.lastname: Sekine
authors.forename: Akihiko
authors.initials: A
authors.lastname: Saito
mesh_terms: D000328:Adult; D000368:Aged; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism / Q000652:urine*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005919:Glomerular Filtration Rate / Q000502:physiology; D006801:Humans; D007668:Kidney / Q000378:metabolism; D026561:Low Density Lipoprotein Receptor-Related Protein-2 / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D055815:Young Adult
chemical_list: D026561:Low Density Lipoprotein Receptor-Related Protein-2