Ibrutinib does not prevent kidney fibrosis following acute and chronic injury

Abstract Recent studies suggested that ibrutinib, a Bruton tyrosine kinase (BTK) inhibitor, developed for the treatment of chronic lymphocytic leukemia, may prevent NLRP3 inflammasome activation in macrophages, IL-1β secretion and subsequent development of inflammation and organ fibrosis. The role o...

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Autores principales:	Julie Belliere, Audrey Casemayou, Eloïse Colliou, Hélène El Hachem, Clément Kounde, Alexis Piedrafita, Guylène Feuillet, Joost P. Schanstra, Stanislas Faguer
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/2020b7952aae4eb88a1c4a7634ff29e2
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spelling	oai:doaj.org-article:2020b7952aae4eb88a1c4a7634ff29e22021-12-02T17:52:12ZIbrutinib does not prevent kidney fibrosis following acute and chronic injury10.1038/s41598-021-91491-x2045-2322https://doaj.org/article/2020b7952aae4eb88a1c4a7634ff29e22021-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-91491-xhttps://doaj.org/toc/2045-2322Abstract Recent studies suggested that ibrutinib, a Bruton tyrosine kinase (BTK) inhibitor, developed for the treatment of chronic lymphocytic leukemia, may prevent NLRP3 inflammasome activation in macrophages, IL-1β secretion and subsequent development of inflammation and organ fibrosis. The role of NLRP3 has been underlined in the various causes of acute kidney injury (AKI), a pathology characterized by high morbimortality and risk of transition toward chronic kidney disease (CKD). We therefore hypothesized that the BTK-inhibitor ibrutinib could be a candidate drug for AKI treatment. Here, we observed in both an AKI model (glycerol-induced rhabdomyolysis) and a model of rapidly progressive kidney fibrosis (unilateral ureteral obstruction), that ibrutinib did not prevent inflammatory cell recruitment in the kidney and fibrosis. Moreover, ibrutinib pre-exposure led to high mortality rate owing to severer rhabdomyolysis and AKI. In vitro, ibrutinib potentiated or had no effect on the secretion of IL-1β by monocytes exposed to uromodulin or myoglobin, two danger-associated molecule patterns proteins involved in the AKI to CKD transition. According to these results, ibrutinib should not be considered a candidate drug for patients developing AKI.Julie BelliereAudrey CasemayouEloïse ColliouHélène El HachemClément KoundeAlexis PiedrafitaGuylène FeuilletJoost P. SchanstraStanislas FaguerNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-8 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Julie Belliere Audrey Casemayou Eloïse Colliou Hélène El Hachem Clément Kounde Alexis Piedrafita Guylène Feuillet Joost P. Schanstra Stanislas Faguer Ibrutinib does not prevent kidney fibrosis following acute and chronic injury
description	Abstract Recent studies suggested that ibrutinib, a Bruton tyrosine kinase (BTK) inhibitor, developed for the treatment of chronic lymphocytic leukemia, may prevent NLRP3 inflammasome activation in macrophages, IL-1β secretion and subsequent development of inflammation and organ fibrosis. The role of NLRP3 has been underlined in the various causes of acute kidney injury (AKI), a pathology characterized by high morbimortality and risk of transition toward chronic kidney disease (CKD). We therefore hypothesized that the BTK-inhibitor ibrutinib could be a candidate drug for AKI treatment. Here, we observed in both an AKI model (glycerol-induced rhabdomyolysis) and a model of rapidly progressive kidney fibrosis (unilateral ureteral obstruction), that ibrutinib did not prevent inflammatory cell recruitment in the kidney and fibrosis. Moreover, ibrutinib pre-exposure led to high mortality rate owing to severer rhabdomyolysis and AKI. In vitro, ibrutinib potentiated or had no effect on the secretion of IL-1β by monocytes exposed to uromodulin or myoglobin, two danger-associated molecule patterns proteins involved in the AKI to CKD transition. According to these results, ibrutinib should not be considered a candidate drug for patients developing AKI.
format	article
author	Julie Belliere Audrey Casemayou Eloïse Colliou Hélène El Hachem Clément Kounde Alexis Piedrafita Guylène Feuillet Joost P. Schanstra Stanislas Faguer
author_facet	Julie Belliere Audrey Casemayou Eloïse Colliou Hélène El Hachem Clément Kounde Alexis Piedrafita Guylène Feuillet Joost P. Schanstra Stanislas Faguer
author_sort	Julie Belliere
title	Ibrutinib does not prevent kidney fibrosis following acute and chronic injury
title_short	Ibrutinib does not prevent kidney fibrosis following acute and chronic injury
title_full	Ibrutinib does not prevent kidney fibrosis following acute and chronic injury
title_fullStr	Ibrutinib does not prevent kidney fibrosis following acute and chronic injury
title_full_unstemmed	Ibrutinib does not prevent kidney fibrosis following acute and chronic injury
title_sort	ibrutinib does not prevent kidney fibrosis following acute and chronic injury
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/2020b7952aae4eb88a1c4a7634ff29e2
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Ibrutinib does not prevent kidney fibrosis following acute and chronic injury

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