Significance of urinary C-megalin excretion in vitamin D metabolism in pre-dialysis CKD patients

• Published in: Scientific reports 2019-02, Vol.9 (1), p.2207-2207, Article 2207
• Main Authors: Toi, Norikazu, Inaba, Masaaki, Ishimura, Eiji, Tsugawa, Naoko, Imanishi, Yasuo, Emoto, Masanori, Hirayama, Yoshiaki, Nakatani, Shinya, Saito, Akihiko, Yamada, Shinsuke
• Format: Article
• Language: English
• Subjects: 25-Hydroxyvitamin D; 692/4022/1585/104; 692/4022/272/1684; Dialysis; Epidermal growth factor receptors; Epithelial cells; Excretion; Exocytosis; Fibroblast growth factor 23; Humanities and Social Sciences; Metabolism; multidisciplinary; Multiple regression analysis; Nephrons; Parathyroid hormone; Protein turnover; Reabsorption; Science; Science (multidisciplinary); Vitamin D
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-019-38613-8

Serum 1,25(OH) 2 D and 24,25(OH) 2 D are decreased in CKD. Megalin in proximal tubular epithelial cells reabsorbs glomerular-filtered 25(OH)D-DBP complex to convert 25(OH)D to 1,25(OH) 2 D and 24,25(OH) 2 D. Urinary C-megalin excretion is increased via exocytosis from injured nephrons overloaded with megalin-mediated protein metabolism. This study investigated the significance of urinary C-megalin excretion in vitamin D metabolism in 153 pre-dialysis CKD patients. Urinary C-megalin was positively associated with urinary protein, β 2 MG and α 1 MG, and exhibited negative correlations with serum 25(OH)D, 1,25(OH) 2 D and 24,25(OH) 2 D. Multiple regression analysis showed that urinary C-megalin had a significantly negative association with 25(OH)D. Serum 1,25(OH) 2 D and 24,25(OH) 2 D, as well as 1,25(OH) 2 D/25(OH)D and 24,25(OH) 2 D/25(OH)D ratios, showed positive correlations with eGFR. Additionally, wholePTH was positively associated with 1,25(OH) 2 D/25(OH)D and 1,25(OH) 2 D/24,25(OH) 2 D, while FGF23 was positively associated with 24,25(OH) 2 D/25(OH)D and negatively with 1,25(OH) 2 D/24,25(OH) 2 D. Urinary C-megalin emerged as an independent factor positively associated with 1,25(OH) 2 D/25(OH)D and 1,25(OH) 2 D/24,25(OH) 2 D. Although 1,25(OH) 2 D and 24,25(OH) 2 D are decreased in CKD patient serum, our findings suggest that PTH and FGF23 retain their effects to regulate vitamin D metabolism even in the kidneys of these patients, while production of 1,25(OH) 2 D and 24,25(OH) 2 D from 25(OH)D is restricted due to either impairment of megalin-mediated reabsorption of the 25(OH)D-DBP complex or reduced renal mass.