急性肝炎患者因 FGF23 生成过多而诱发的严重低磷血症:从床边到工作台。

IF 3.9 2区 医学 Q1 UROLOGY & NEPHROLOGY Clinical Kidney Journal Pub Date : 2024-10-09 eCollection Date: 2024-11-01 DOI:10.1093/ckj/sfae307
Aghiles Hamroun, Nihad Boukrout, Christelle Cauffiez, Sandy Fellah, Cynthia Van der Hauwaert, Nicolas Pottier, Romuald Mentaverri, Jeremy Zaworski, Viviane Gnemmi, Jean-Baptiste Gibier, Emmanuel Letavernier, Alexandre Louvet, François Provôt, Rémi Lenain, Mehdi Maanaoui, François Glowacki, Arnaud Lionet
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引用次数: 0

摘要

背景:虽然有人认为肝脏在慢性情况下会产生 FGF23,但没有数据表明急性肝脏 FGF23 的产生会导致低磷血症。根据两例急性肝炎导致的严重低磷血症的临床观察,我们的研究探讨了急性肝脏表达 FGF23 的假设:方法:与肝纤维化或健康肝脏对照组相比,对人类和鼠类急性肝炎肝脏组织学标本进行回顾性分析,从定性(原位杂交)和定量(相对 FGF23 基因表达和蛋白生成)两方面估计 FGF23 的肝脏表达:第一个临床病例是急性酒精性肝炎,并发磷酸盐糖尿病引起的深度低磷血症,结果显示 FGF23 C 端部分(cFGF23)和生物非接触形式(iFGF23,39 751 RU/mL,N:21-91;和 228.6 pg/mL,N:22.7-93.1)均大量产生。第二例与红细胞原卟啉症有关的急性肝炎病例也出现了类似的异常。在这两个病例中,均未发现导致肾磷酸盐消耗的其他原因,而且在肝平衡和 FGF23 水平恢复正常的同时,水电解质紊乱也随之消失。急性肝炎与肝硬化和健康肝脏相比的组织学数据证实了我们关于肝脏 FGF23 过度分泌的假设。此外,小鼠模型显示,与健康肝脏相比,急性肝炎和肝硬化的 FGF23 mRNA 相对肝脏表达量明显增加(分别为 60.55 ± 16.75 和 3.70 ± 0.87 vs 1.00 ± 0.65,均为 P):这项转化研究提出了急性肝炎患者肝脏产生过多 FGF23 导致肾脏磷酸盐消耗的假说。
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Severe hypophosphatemia induced by excessive production of FGF23 in acute hepatitis: from bedside to bench.

Background: Although hepatic production of FGF23 has been suggested in chronic settings, there are no data indicating hypophosphatemia resulting from acute hepatic FGF23 production. Based on two clinical observations of profound hypophosphatemia in the setting of acute hepatitis, our study investigates the hypothesis of acute FGF23 liver expression.

Methods: Retrospective analyses were conducted to estimate FGF23 liver expression both qualitatively (in situ hybridization) and quantitatively (relative FGF23 gene expression and protein production) on histological specimens of human and murine acute hepatitis livers, compared with controls of hepatic fibrosis or healthy liver.

Results: The index clinical case involves acute alcoholic hepatitis complicated by profound hypophosphatemia due to phosphate diabetes, revealing a major production of both FGF23 C-terminal fraction (cFGF23) and bio-intact form (iFGF23, 39 751 RU/mL, N: 21-91; and 228.6 pg/mL, N: 22.7-93.1, respectively). A second case of acute hepatitis related to erythrocytic protoporphyria also exhibited comparable abnormalities. In both cases, no other cause of renal phosphate wasting was identified, and the hydroelectrolytic disorders disappeared in parallel with normalization of the liver balance and FGF23 levels. Histological data of acute hepatitis compared with cirrhosis and healthy liver confirmed our hypothesis of hepatic FGF23 overproduction. Furthermore, mouse models showed a significant increase in FGF23 mRNA relative liver expression in acute hepatitis and a moderate increase in cirrhosis, compared with healthy liver (respectively 60.55 ± 16.75 and 3.70 ± 0.87 vs 1.00 ± 0.65, both P < .05). These findings were also confirmed at the protein level.

Conclusion: This translational study raises the hypothesis of renal phosphate wasting induced by excessive hepatic production of FGF23 in case of acute hepatitis.

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来源期刊
Clinical Kidney Journal
Clinical Kidney Journal Medicine-Transplantation
CiteScore
6.70
自引率
10.90%
发文量
242
审稿时长
8 weeks
期刊介绍: About the Journal Clinical Kidney Journal: Clinical and Translational Nephrology (ckj), an official journal of the ERA-EDTA (European Renal Association-European Dialysis and Transplant Association), is a fully open access, online only journal publishing bimonthly. The journal is an essential educational and training resource integrating clinical, translational and educational research into clinical practice. ckj aims to contribute to a translational research culture among nephrologists and kidney pathologists that helps close the gap between basic researchers and practicing clinicians and promote sorely needed innovation in the Nephrology field. All research articles in this journal have undergone peer review.
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