Significance of Urinary C-megalin Excretion in Vitamin D Metabolism in Pre-dialysis CKD Patients

Overview

Journal Sci Rep

Specialty Science

Date 2019 Feb 20

PMID 30778159

Citations 6

Authors

Norikazu Toi

Masaaki Inaba

Eiji Ishimura

Naoko Tsugawa

Yasuo Imanishi

Masanori Emoto

Yoshiaki Hirayama

Shinya Nakatani

Akihiko Saito

Shinsuke Yamada

Affiliations

Soon will be listed here.

Abstract

Serum 1,25(OH)D and 24,25(OH)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)D and 24,25(OH)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, βMG and αMG, and exhibited negative correlations with serum 25(OH)D, 1,25(OH)D and 24,25(OH)D. Multiple regression analysis showed that urinary C-megalin had a significantly negative association with 25(OH)D. Serum 1,25(OH)D and 24,25(OH)D, as well as 1,25(OH)D/25(OH)D and 24,25(OH)D/25(OH)D ratios, showed positive correlations with eGFR. Additionally, wholePTH was positively associated with 1,25(OH)D/25(OH)D and 1,25(OH)D/24,25(OH)D, while FGF23 was positively associated with 24,25(OH)D/25(OH)D and negatively with 1,25(OH)D/24,25(OH)D. Urinary C-megalin emerged as an independent factor positively associated with 1,25(OH)D/25(OH)D and 1,25(OH)D/24,25(OH)D. Although 1,25(OH)D and 24,25(OH)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)D and 24,25(OH)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.

Citing Articles

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