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在未进行透析的慢性肾脏病患者中，尿 C-Megalin 排泄在维生素 D 代谢中的意义。

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

机构信息

Department of Metabolism, Endocrinology, and Molecular Medicine, Osaka City University Graduate School of Medicine, Osaka, Japan.

Department of Nephrology, Osaka City University Graduate School of Medicine, Osaka, Japan.

出版信息

Sci Rep. 2019 Feb 18;9(1):2207. doi: 10.1038/s41598-019-38613-8.

DOI:10.1038/s41598-019-38613-8
PMID:30778159
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6379559/
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.

摘要

血清 1,25(OH)D 和 24,25(OH)D 在 CKD 中降低。近端肾小管上皮细胞中的 megalin 重吸收肾小球滤过的 25(OH)D-DBP 复合物，将 25(OH)D 转化为 1,25(OH)D 和 24,25(OH)D。受损的肾脏中 megalin 介导的蛋白质代谢过载，通过胞吐作用导致尿中 C-megalin 排泄增加。本研究探讨了 153 例未透析 CKD 患者尿液中 C-megalin 排泄在维生素 D 代谢中的意义。尿 C-megalin 与尿蛋白、βMG 和 αMG 呈正相关，与血清 25(OH)D、1,25(OH)D 和 24,25(OH)D 呈负相关。多元回归分析显示，尿 C-megalin 与 25(OH)D 呈显著负相关。血清 1,25(OH)D 和 24,25(OH)D 以及 1,25(OH)D/25(OH)D 和 24,25(OH)D/25(OH)D 比值与 eGFR 呈正相关。此外，全段甲状旁腺素与 1,25(OH)D/25(OH)D 和 1,25(OH)D/24,25(OH)D 呈正相关，而 FGF23 与 24,25(OH)D/25(OH)D 呈正相关，与 1,25(OH)D/24,25(OH)D 呈负相关。尿 C-megalin 是与 1,25(OH)D/25(OH)D 和 1,25(OH)D/24,25(OH)D 呈正相关的独立因素。尽管 CKD 患者血清中 1,25(OH)D 和 24,25(OH)D 降低，但我们的研究结果表明，即使在这些患者的肾脏中，PTH 和 FGF23 仍能发挥作用来调节维生素 D 代谢，而 25(OH)D-DBP 复合物的 megalin 介导重吸收受损或肾脏质量减少，限制了 1,25(OH)D 和 24,25(OH)D 的生成。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2ffa/6379559/3b0c69d1eddd/41598_2019_38613_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2ffa/6379559/3d0fdefb47fc/41598_2019_38613_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2ffa/6379559/7d7b8274cef1/41598_2019_38613_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2ffa/6379559/ad1836ac0838/41598_2019_38613_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2ffa/6379559/3c91aeefb44e/41598_2019_38613_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2ffa/6379559/3b0c69d1eddd/41598_2019_38613_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2ffa/6379559/3d0fdefb47fc/41598_2019_38613_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2ffa/6379559/7d7b8274cef1/41598_2019_38613_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2ffa/6379559/ad1836ac0838/41598_2019_38613_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2ffa/6379559/3c91aeefb44e/41598_2019_38613_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2ffa/6379559/3b0c69d1eddd/41598_2019_38613_Fig5_HTML.jpg

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