Abstract: FR-PO279

Association between Urinary Full-Length Megalin and Serum Vitamin D Metabolites in CKD

Session Information

Category: Mineral Disease

  • 1202 Mineral Disease: Vitamin D, PTH, FGF-23


  • Toi, Norikazu, Osaka City University Graduate School of Medicine, Osaka, Japan
  • Yamada, Shinsuke, a. Department of Metabolism, Endocrinology, and Molecular Medicine, Osaka City University Graduate School of Medicine, Osaka, Japan
  • Ishimura, Eiji, Meijibashi Hospital, Osaka, Japan
  • Nakatani, Ayumi, Osaka City University Graduate School of Medicine, Osaka, Japan
  • Nakatani, Shinya, Osaka City University Graduate School of Medicine, Osaka, Japan
  • Hirayama, Yoshiaki, Denka-seiken co., ltd., Gosen-shi, Japan
  • Tsugawa, Naoko, Osaka Shoin Women''s University, Higashi-osaka, Japan
  • Saito, Akihiko, Niigata University, Niigata, Japan
  • Inaba, Masaaki, Osaka City University Graduate School of Medicine, Osaka, Japan

25-hydroxyvitamin D (25D) bound to vitamin D binding protein is reabsorbed by megalin, which is a membrane receptor highly expressed on proximal tubular epithelial cells. Increase in urinary megalin excretion due to tubular injury may affect vitamin D metabolism in chronic kidney disease (CKD) patients. The aim of the present study was to investigate whether increase in urinary excretion of megalin may have harmful effects on vitamin D metabolism in CKD patients.


One hundred fifty three CKD patients with eGFR less than 60 mL/min/1.73m2 (101 males and 53 females, 64.7 ± 14.6 years) were recruited in this cross-sectional study. Urinary full-length megalin (C-megalin) and serum vitamin D metabolites (25D, 1α,25-dihydroxyvitamin D (1,25D), 24,25-dihydroxyvitamin D (24,25D) were measured.


The mean levels of eGFR, serum levels of 25D, and urinary levels of C-megalin were 29.0 ± 15.8 mL/min/1.73m2, 15.1 ± 6.2 ng/mL and 0.9 ± 1.1 pmol/gCr, respectively. In a simple regression analysis, 25D exhibited significant and negative correlation with urinary C-megalin (ρ = - 0.310, p = 0.0002), and urinary C-megalin had a significant and positive correlation with urinary protein (ρ = 0.603, p <0.0001), although both 25D and urinary C-megalin was not significantly correlated with eGFR. In a multiple regression analysis adjusted by age, gender, BMI, presence of diabetes, serum albumin, eGFR, serum PTH, serum FGF-23, and urinary C-megalin, urinary C-megalin was associated significantly with 25D in a negative manner (β = - 0.302, p = 0.0027). Furthermore, both 1,25D (β = 0.227, p = 0.0013) and 24,25D (β = 0.482, p <0.0001) were positively associated with 25D. The ratio of 1,25D/24,25D, which is a putative indicator of 1α-hydroxylase activity, was significantly, positively affected by urinary C-megalin independently to other clinical confounders.


This study demonstrated that serum 25D decreases with an increase in urinary C-megalin, and that serum 1,25D and 24,25D decrease with a decrease in 25D in CKD patients. Thus, decreased 25D induced by increased urinary C-megalin, which is a representative of tubular injury, affects decrease in 1,25D, suggesting the clinical importance of renal tubular dysfunction in vitamin D metabolism in CKD patients.