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Renal Inflammation and Innate Immune Activation Underlie the Transition From Gentamicin-Induced Acute Kidney Injury to Renal Fibrosis

Subjects recovering from acute kidney injury (AKI) are at risk of developing chronic kidney disease (CKD). The mechanisms underlying this transition are unclear and may involve sustained activation of renal innate immunity, with resulting renal inflammation and fibrosis. We investigated whether the...

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Autores principales: Albino, Amanda Helen, Zambom, Fernanda Florencia Fregnan, Foresto-Neto, Orestes, Oliveira, Karin Carneiro, Ávila, Victor Ferreira, Arias, Simone Costa Alarcon, Seguro, Antonio Carlos, Malheiros, Denise Maria Avancini Costa, Camara, Niels Olsen Saraiva, Fujihara, Clarice Kazue, Zatz, Roberto
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8293269/
https://www.ncbi.nlm.nih.gov/pubmed/34305624
http://dx.doi.org/10.3389/fphys.2021.606392
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author Albino, Amanda Helen
Zambom, Fernanda Florencia Fregnan
Foresto-Neto, Orestes
Oliveira, Karin Carneiro
Ávila, Victor Ferreira
Arias, Simone Costa Alarcon
Seguro, Antonio Carlos
Malheiros, Denise Maria Avancini Costa
Camara, Niels Olsen Saraiva
Fujihara, Clarice Kazue
Zatz, Roberto
author_facet Albino, Amanda Helen
Zambom, Fernanda Florencia Fregnan
Foresto-Neto, Orestes
Oliveira, Karin Carneiro
Ávila, Victor Ferreira
Arias, Simone Costa Alarcon
Seguro, Antonio Carlos
Malheiros, Denise Maria Avancini Costa
Camara, Niels Olsen Saraiva
Fujihara, Clarice Kazue
Zatz, Roberto
author_sort Albino, Amanda Helen
collection PubMed
description Subjects recovering from acute kidney injury (AKI) are at risk of developing chronic kidney disease (CKD). The mechanisms underlying this transition are unclear and may involve sustained activation of renal innate immunity, with resulting renal inflammation and fibrosis. We investigated whether the NF-κB system and/or the NLRP3 inflammasome pathway remain activated after the resolution of AKI induced by gentamicin (GT) treatment, thus favoring the development of CKD. Male Munich-Wistar rats received daily subcutaneous injections of GT, 80 mg/kg, for 9 days. Control rats received vehicle only (NC). Rats were studied at 1, 30, and 180 days after GT treatment was ceased. On Day 1, glomerular ischemia (ISCH), tubular necrosis, albuminuria, creatinine retention, and tubular dysfunction were noted, in association with prominent renal infiltration by macrophages and myofibroblasts, along with increased renal abundance of TLR4, IL-6, and IL1β. Regression of functional and structural changes occurred on Day 30. However, the renal content of IL-1β was still elevated at this time, while the local renin-angiotensin system remained activated, and interstitial fibrosis became evident. On Day 180, recurring albuminuria and mild glomerulosclerosis were seen, along with ISCH and unabated interstitial fibrosis, whereas macrophage infiltration was still evident. GT-induced AKI activates innate immunity and promotes renal inflammation. Persistence of these abnormalities provides a plausible explanation for the transition of AKI to CKD observed in a growing number of patients.
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spelling pubmed-82932692021-07-22 Renal Inflammation and Innate Immune Activation Underlie the Transition From Gentamicin-Induced Acute Kidney Injury to Renal Fibrosis Albino, Amanda Helen Zambom, Fernanda Florencia Fregnan Foresto-Neto, Orestes Oliveira, Karin Carneiro Ávila, Victor Ferreira Arias, Simone Costa Alarcon Seguro, Antonio Carlos Malheiros, Denise Maria Avancini Costa Camara, Niels Olsen Saraiva Fujihara, Clarice Kazue Zatz, Roberto Front Physiol Physiology Subjects recovering from acute kidney injury (AKI) are at risk of developing chronic kidney disease (CKD). The mechanisms underlying this transition are unclear and may involve sustained activation of renal innate immunity, with resulting renal inflammation and fibrosis. We investigated whether the NF-κB system and/or the NLRP3 inflammasome pathway remain activated after the resolution of AKI induced by gentamicin (GT) treatment, thus favoring the development of CKD. Male Munich-Wistar rats received daily subcutaneous injections of GT, 80 mg/kg, for 9 days. Control rats received vehicle only (NC). Rats were studied at 1, 30, and 180 days after GT treatment was ceased. On Day 1, glomerular ischemia (ISCH), tubular necrosis, albuminuria, creatinine retention, and tubular dysfunction were noted, in association with prominent renal infiltration by macrophages and myofibroblasts, along with increased renal abundance of TLR4, IL-6, and IL1β. Regression of functional and structural changes occurred on Day 30. However, the renal content of IL-1β was still elevated at this time, while the local renin-angiotensin system remained activated, and interstitial fibrosis became evident. On Day 180, recurring albuminuria and mild glomerulosclerosis were seen, along with ISCH and unabated interstitial fibrosis, whereas macrophage infiltration was still evident. GT-induced AKI activates innate immunity and promotes renal inflammation. Persistence of these abnormalities provides a plausible explanation for the transition of AKI to CKD observed in a growing number of patients. Frontiers Media S.A. 2021-07-07 /pmc/articles/PMC8293269/ /pubmed/34305624 http://dx.doi.org/10.3389/fphys.2021.606392 Text en Copyright © 2021 Albino, Zambom, Foresto-Neto, Oliveira, Ávila, Arias, Seguro, Malheiros, Camara, Fujihara and Zatz. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Physiology
Albino, Amanda Helen
Zambom, Fernanda Florencia Fregnan
Foresto-Neto, Orestes
Oliveira, Karin Carneiro
Ávila, Victor Ferreira
Arias, Simone Costa Alarcon
Seguro, Antonio Carlos
Malheiros, Denise Maria Avancini Costa
Camara, Niels Olsen Saraiva
Fujihara, Clarice Kazue
Zatz, Roberto
Renal Inflammation and Innate Immune Activation Underlie the Transition From Gentamicin-Induced Acute Kidney Injury to Renal Fibrosis
title Renal Inflammation and Innate Immune Activation Underlie the Transition From Gentamicin-Induced Acute Kidney Injury to Renal Fibrosis
title_full Renal Inflammation and Innate Immune Activation Underlie the Transition From Gentamicin-Induced Acute Kidney Injury to Renal Fibrosis
title_fullStr Renal Inflammation and Innate Immune Activation Underlie the Transition From Gentamicin-Induced Acute Kidney Injury to Renal Fibrosis
title_full_unstemmed Renal Inflammation and Innate Immune Activation Underlie the Transition From Gentamicin-Induced Acute Kidney Injury to Renal Fibrosis
title_short Renal Inflammation and Innate Immune Activation Underlie the Transition From Gentamicin-Induced Acute Kidney Injury to Renal Fibrosis
title_sort renal inflammation and innate immune activation underlie the transition from gentamicin-induced acute kidney injury to renal fibrosis
topic Physiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8293269/
https://www.ncbi.nlm.nih.gov/pubmed/34305624
http://dx.doi.org/10.3389/fphys.2021.606392
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