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
{"title":"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。","authors":"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","doi":"10.1093/ckj/sfae307","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>Retrospective analyses were conducted to estimate FGF23 liver expression both qualitatively (<i>in situ</i> 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.</p><p><strong>Results: </strong>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 <i>P</i> < .05). These findings were also confirmed at the protein level.</p><p><strong>Conclusion: </strong>This translational study raises the hypothesis of renal phosphate wasting induced by excessive hepatic production of FGF23 in case of acute hepatitis.</p>","PeriodicalId":10435,"journal":{"name":"Clinical Kidney Journal","volume":"17 11","pages":"sfae307"},"PeriodicalIF":3.9000,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11548962/pdf/","citationCount":"0","resultStr":"{\"title\":\"Severe hypophosphatemia induced by excessive production of FGF23 in acute hepatitis: from bedside to bench.\",\"authors\":\"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\",\"doi\":\"10.1093/ckj/sfae307\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>Retrospective analyses were conducted to estimate FGF23 liver expression both qualitatively (<i>in situ</i> 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.</p><p><strong>Results: </strong>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 <i>P</i> < .05). These findings were also confirmed at the protein level.</p><p><strong>Conclusion: </strong>This translational study raises the hypothesis of renal phosphate wasting induced by excessive hepatic production of FGF23 in case of acute hepatitis.</p>\",\"PeriodicalId\":10435,\"journal\":{\"name\":\"Clinical Kidney Journal\",\"volume\":\"17 11\",\"pages\":\"sfae307\"},\"PeriodicalIF\":3.9000,\"publicationDate\":\"2024-10-09\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11548962/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Clinical Kidney Journal\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1093/ckj/sfae307\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/11/1 0:00:00\",\"PubModel\":\"eCollection\",\"JCR\":\"Q1\",\"JCRName\":\"UROLOGY & NEPHROLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Clinical Kidney Journal","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1093/ckj/sfae307","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/11/1 0:00:00","PubModel":"eCollection","JCR":"Q1","JCRName":"UROLOGY & NEPHROLOGY","Score":null,"Total":0}
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.
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.