title: Significance of urinary full-length megalin in patients with IgA nephropathy.
abstract: OBJECTIVE
  Megalin is highly expressed at the apical membranes of proximal tubular epithelial cells. A urinary full-length megalin (C-megalin) assay is linked to the severity of diabetic nephropathy in type 2 diabetes. This study examined the relationship between levels of urinary C-megalin and histological findings in adult patients with IgA nephropathy (IgAN).
  
  
  METHODS
  Urine samples voided in the morning on the day of renal biopsy were obtained from 73 patients with IgAN (29 men and 44 women; mean age, 33 years) and 5 patients with membranous nephropathy (MN). Renal pathologic variables were analyzed using the Oxford classification of IgAN, the Shigematsu classification and the Clinical Guidelines of IgAN in Japan. The levels of urinary C-megalin were measured by sandwich ELISA.
  
  
  RESULTS
  Histological analysis based on the Oxford classification revealed that the levels of urinary C-megalin were correlated with mesangial hypercellularity in IgAN patients (OR = 1.76, 95% CI: 1.04-3.27, P<0.05). There was a significant correlation between the levels of urinary C-megalin and the severity of chronic extracapillary abnormalities according to the Shigematsu classification in IgAN patients (β = 0.33, P = 0.008). The levels of urinary C-megalin were significantly higher in all risk levels of IgAN patients requiring dialysis using the Clinical Guidelines of IgAN in Japan than in the control group. The levels of urinary C-megalin were significantly higher in the high risk and very high risk grades than in the low risk grade (P<0.05). The levels of urinary C-megalin were significantly higher in MN patients compared to the control group.
  
  
  CONCLUSIONS
  The levels of urinary C-megalin are associated with histological abnormalities in adult IgAN patients. There is a possibility that urinary C-megalin is an independent predictor of disease progression of IgAN. In addition, our results suggest that urinary C-megalin is a marker of glomerular abnormalities in various glomerular diseases as well as IgAN.
authors.affiliation: Division of Nephrology, Juntendo University Faculty of Medicine, Tokyo, Japan; TMK project, Medical Innovation Center, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors.forename: Takuto
authors.initials: T
authors.lastname: Seki
authors.affiliation: Division of Nephrology, Juntendo University Faculty of Medicine, Tokyo, Japan; TMK project, Medical Innovation Center, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Asanuma
authors.affiliation: Division of Nephrology, Juntendo University Faculty of Medicine, Tokyo, Japan.
authors.forename: Rin
authors.initials: R
authors.lastname: Asao
authors.affiliation: Division of Nephrology, Juntendo University Faculty of Medicine, Tokyo, Japan; TMK project, Medical Innovation Center, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors.forename: Kanae
authors.initials: K
authors.lastname: Nonaka
authors.affiliation: Division of Nephrology, Juntendo University Faculty of Medicine, Tokyo, Japan.
authors.forename: Yu
authors.initials: Y
authors.lastname: Sasaki
authors.affiliation: Division of Nephrology, Juntendo University Faculty of Medicine, Tokyo, Japan.
authors.forename: Juan Alejandro
authors.initials: JA
authors.lastname: Oliva Trejo
authors.affiliation: Reagents Development Department, Denka Seiken Co. Ltd., Niigata, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kurosawa
authors.affiliation: Reagents Development Department, Denka Seiken Co. Ltd., Niigata, Japan.
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Hirayama
authors.affiliation: Division of Nephrology, Juntendo University Faculty of Medicine, Tokyo, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Horikoshi
authors.affiliation: Division of Nephrology, Juntendo University Faculty of Medicine, Tokyo, Japan.
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Tomino
authors.affiliation: Department of Applied Molecular Medicine, Niigata University Graduate School of Medicine and Dental Sciences, Niigata, Japan.
authors.forename: Akihiko
authors.initials: A
authors.lastname: Saito
mesh_terms: D000118:Acetylglucosaminidase / Q000652:urine; D000328:Adult; D000368:Aged; D000510:Alpha-Globulins / Q000652:urine; D015415:Biomarkers / Q000652:urine; D005260:Female; D005786:Gene Expression Regulation; D005922:Glomerulonephritis, IGA / Q000473:pathology / Q000628:therapy / Q000652:urine*; D006801:Humans; D007668:Kidney / Q000473:pathology; D026561:Low Density Lipoprotein Receptor-Related Protein-2 / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D006435:Renal Dialysis; D012306:Risk; D001613:beta 2-Microglobulin / Q000652:urine
chemical_list: D000510:Alpha-Globulins; D015415:Biomarkers; D026561:Low Density Lipoprotein Receptor-Related Protein-2; C016001:alpha-1-microglobulin; D001613:beta 2-Microglobulin; D000118:Acetylglucosaminidase