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Alkalosis-induced hypoventilation in cystic fibrosis: The importance of efficient renal adaptation

The lungs and kidneys are pivotal organs in the regulation of body acid–base homeostasis. In cystic fibrosis (CF), the impaired renal ability to excrete an excess amount of HCO(3)(−) into the urine leads to metabolic alkalosis [P. Berg et al., J. Am. Soc. Nephrol. 31, 1711–1727 (2020); F. Al-Ghimlas...

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Autores principales: Berg, Peder, Andersen, Jesper Frank, Sørensen, Mads Vaarby, Wang, Tobias, Malte, Hans, Leipziger, Jens
Formato: Online Artículo Texto
Lenguaje:English
Publicado: National Academy of Sciences 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8872776/
https://www.ncbi.nlm.nih.gov/pubmed/35173044
http://dx.doi.org/10.1073/pnas.2116836119
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author Berg, Peder
Andersen, Jesper Frank
Sørensen, Mads Vaarby
Wang, Tobias
Malte, Hans
Leipziger, Jens
author_facet Berg, Peder
Andersen, Jesper Frank
Sørensen, Mads Vaarby
Wang, Tobias
Malte, Hans
Leipziger, Jens
author_sort Berg, Peder
collection PubMed
description The lungs and kidneys are pivotal organs in the regulation of body acid–base homeostasis. In cystic fibrosis (CF), the impaired renal ability to excrete an excess amount of HCO(3)(−) into the urine leads to metabolic alkalosis [P. Berg et al., J. Am. Soc. Nephrol. 31, 1711–1727 (2020); F. Al-Ghimlas, M. E. Faughnan, E. Tullis, Open Respir. Med. J. 6, 59–62 (2012)]. This is caused by defective HCO(3)(−) secretion in the β-intercalated cells of the collecting duct that requires both the cystic fibrosis transmembrane conductance regulator (CFTR) and pendrin for normal function [P. Berg et al., J. Am. Soc. Nephrol. 31, 1711–1727 (2020)]. We studied the ventilatory consequences of acute oral base loading in normal, pendrin knockout (KO), and CFTR KO mice. In wild-type mice, oral base loading induced a dose-dependent metabolic alkalosis, fast urinary removal of base, and a moderate base load did not perturb ventilation. In contrast, CFTR and pendrin KO mice, which are unable to rapidly excrete excess base into the urine, developed a marked and transient depression of ventilation when subjected to the same base load. Therefore, swift renal base elimination in response to an acute oral base load is a necessary physiological function to avoid ventilatory depression. The transient urinary alkalization in the postprandial state is suggested to have evolved for proactive avoidance of hypoventilation. In CF, metabolic alkalosis may contribute to the commonly reduced lung function via a suppression of ventilatory drive.
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spelling pubmed-88727762022-08-16 Alkalosis-induced hypoventilation in cystic fibrosis: The importance of efficient renal adaptation Berg, Peder Andersen, Jesper Frank Sørensen, Mads Vaarby Wang, Tobias Malte, Hans Leipziger, Jens Proc Natl Acad Sci U S A Biological Sciences The lungs and kidneys are pivotal organs in the regulation of body acid–base homeostasis. In cystic fibrosis (CF), the impaired renal ability to excrete an excess amount of HCO(3)(−) into the urine leads to metabolic alkalosis [P. Berg et al., J. Am. Soc. Nephrol. 31, 1711–1727 (2020); F. Al-Ghimlas, M. E. Faughnan, E. Tullis, Open Respir. Med. J. 6, 59–62 (2012)]. This is caused by defective HCO(3)(−) secretion in the β-intercalated cells of the collecting duct that requires both the cystic fibrosis transmembrane conductance regulator (CFTR) and pendrin for normal function [P. Berg et al., J. Am. Soc. Nephrol. 31, 1711–1727 (2020)]. We studied the ventilatory consequences of acute oral base loading in normal, pendrin knockout (KO), and CFTR KO mice. In wild-type mice, oral base loading induced a dose-dependent metabolic alkalosis, fast urinary removal of base, and a moderate base load did not perturb ventilation. In contrast, CFTR and pendrin KO mice, which are unable to rapidly excrete excess base into the urine, developed a marked and transient depression of ventilation when subjected to the same base load. Therefore, swift renal base elimination in response to an acute oral base load is a necessary physiological function to avoid ventilatory depression. The transient urinary alkalization in the postprandial state is suggested to have evolved for proactive avoidance of hypoventilation. In CF, metabolic alkalosis may contribute to the commonly reduced lung function via a suppression of ventilatory drive. National Academy of Sciences 2022-02-16 2022-02-22 /pmc/articles/PMC8872776/ /pubmed/35173044 http://dx.doi.org/10.1073/pnas.2116836119 Text en https://creativecommons.org/licenses/by-nc-nd/4.0/This article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND) (https://creativecommons.org/licenses/by-nc-nd/4.0/) .
spellingShingle Biological Sciences
Berg, Peder
Andersen, Jesper Frank
Sørensen, Mads Vaarby
Wang, Tobias
Malte, Hans
Leipziger, Jens
Alkalosis-induced hypoventilation in cystic fibrosis: The importance of efficient renal adaptation
title Alkalosis-induced hypoventilation in cystic fibrosis: The importance of efficient renal adaptation
title_full Alkalosis-induced hypoventilation in cystic fibrosis: The importance of efficient renal adaptation
title_fullStr Alkalosis-induced hypoventilation in cystic fibrosis: The importance of efficient renal adaptation
title_full_unstemmed Alkalosis-induced hypoventilation in cystic fibrosis: The importance of efficient renal adaptation
title_short Alkalosis-induced hypoventilation in cystic fibrosis: The importance of efficient renal adaptation
title_sort alkalosis-induced hypoventilation in cystic fibrosis: the importance of efficient renal adaptation
topic Biological Sciences
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8872776/
https://www.ncbi.nlm.nih.gov/pubmed/35173044
http://dx.doi.org/10.1073/pnas.2116836119
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