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Suppressed renoprotective purines in COVID-19 patients with acute kidney injury

Acute kidney injury (AKI) is common in patients hospitalized for COVID-19, complicating their clinical course and contributing to worse outcomes. Animal studies show that adenosine, inosine and guanosine protect the kidney against some types of AKI. However, until now there was no evidence in patien...

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Autores principales: Jackson, Edwin K., Kitsios, Georgios D., Lu, Michael Y., Schaefer, Caitlin M., Kessinger, Cathy J., McVerry, Bryan J., Morris, Alison, Macatangay, Bernard J. C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9574168/
https://www.ncbi.nlm.nih.gov/pubmed/36253495
http://dx.doi.org/10.1038/s41598-022-22349-z
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author Jackson, Edwin K.
Kitsios, Georgios D.
Lu, Michael Y.
Schaefer, Caitlin M.
Kessinger, Cathy J.
McVerry, Bryan J.
Morris, Alison
Macatangay, Bernard J. C.
author_facet Jackson, Edwin K.
Kitsios, Georgios D.
Lu, Michael Y.
Schaefer, Caitlin M.
Kessinger, Cathy J.
McVerry, Bryan J.
Morris, Alison
Macatangay, Bernard J. C.
author_sort Jackson, Edwin K.
collection PubMed
description Acute kidney injury (AKI) is common in patients hospitalized for COVID-19, complicating their clinical course and contributing to worse outcomes. Animal studies show that adenosine, inosine and guanosine protect the kidney against some types of AKI. However, until now there was no evidence in patients supporting the possibility that abnormally low kidney levels of adenosine, inosine and guanosine contribute to AKI. Here, we addressed the question as to whether these renoprotective purines are altered in the urine of COVID-19 patients with AKI. Purines were measured by employing ultra-high-performance liquid chromatography-tandem mass spectrometry with stable-isotope-labeled internal standards for each purine of interest. Compared with COVID-19 patients without AKI (n = 23), COVID-19 patients with AKI (n = 20) had significantly lower urine levels of adenosine (P < 0.0001), inosine (P = 0.0008), and guanosine (P = 0.0008) (medians reduced by 85%, 48% and 61%, respectively) and lower levels (P = 0.0003; median reduced by 67%) of the 2nd messenger for A(2A) and A(2B) adenosine receptors, i.e., 3’,5’-cAMP. Moreover, in COVID-19 patients with AKI, urine levels of 8-aminoguanine (endogenous inhibitor of inosine and guanosine metabolism) were nearly abolished (P < 0.0001). In contrast, the “upstream” precursors of renoprotective purines, namely 5’-AMP and 5’-GMP, were not significantly altered in COVID-19 patients with AKI, suggesting defective conversion of these precursors by CD73 (converts 5’-AMP to adenosine and 5’-GMP to guanosine). These findings imply that an imbalance in renoprotective purines may contribute to AKI in COVID-19 patients and that pharmacotherapy targeted to restore levels of renoprotective purines may attenuate the risk of AKI in susceptible patients with COVID-19.
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spelling pubmed-95741682022-10-17 Suppressed renoprotective purines in COVID-19 patients with acute kidney injury Jackson, Edwin K. Kitsios, Georgios D. Lu, Michael Y. Schaefer, Caitlin M. Kessinger, Cathy J. McVerry, Bryan J. Morris, Alison Macatangay, Bernard J. C. Sci Rep Article Acute kidney injury (AKI) is common in patients hospitalized for COVID-19, complicating their clinical course and contributing to worse outcomes. Animal studies show that adenosine, inosine and guanosine protect the kidney against some types of AKI. However, until now there was no evidence in patients supporting the possibility that abnormally low kidney levels of adenosine, inosine and guanosine contribute to AKI. Here, we addressed the question as to whether these renoprotective purines are altered in the urine of COVID-19 patients with AKI. Purines were measured by employing ultra-high-performance liquid chromatography-tandem mass spectrometry with stable-isotope-labeled internal standards for each purine of interest. Compared with COVID-19 patients without AKI (n = 23), COVID-19 patients with AKI (n = 20) had significantly lower urine levels of adenosine (P < 0.0001), inosine (P = 0.0008), and guanosine (P = 0.0008) (medians reduced by 85%, 48% and 61%, respectively) and lower levels (P = 0.0003; median reduced by 67%) of the 2nd messenger for A(2A) and A(2B) adenosine receptors, i.e., 3’,5’-cAMP. Moreover, in COVID-19 patients with AKI, urine levels of 8-aminoguanine (endogenous inhibitor of inosine and guanosine metabolism) were nearly abolished (P < 0.0001). In contrast, the “upstream” precursors of renoprotective purines, namely 5’-AMP and 5’-GMP, were not significantly altered in COVID-19 patients with AKI, suggesting defective conversion of these precursors by CD73 (converts 5’-AMP to adenosine and 5’-GMP to guanosine). These findings imply that an imbalance in renoprotective purines may contribute to AKI in COVID-19 patients and that pharmacotherapy targeted to restore levels of renoprotective purines may attenuate the risk of AKI in susceptible patients with COVID-19. Nature Publishing Group UK 2022-10-17 /pmc/articles/PMC9574168/ /pubmed/36253495 http://dx.doi.org/10.1038/s41598-022-22349-z Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Jackson, Edwin K.
Kitsios, Georgios D.
Lu, Michael Y.
Schaefer, Caitlin M.
Kessinger, Cathy J.
McVerry, Bryan J.
Morris, Alison
Macatangay, Bernard J. C.
Suppressed renoprotective purines in COVID-19 patients with acute kidney injury
title Suppressed renoprotective purines in COVID-19 patients with acute kidney injury
title_full Suppressed renoprotective purines in COVID-19 patients with acute kidney injury
title_fullStr Suppressed renoprotective purines in COVID-19 patients with acute kidney injury
title_full_unstemmed Suppressed renoprotective purines in COVID-19 patients with acute kidney injury
title_short Suppressed renoprotective purines in COVID-19 patients with acute kidney injury
title_sort suppressed renoprotective purines in covid-19 patients with acute kidney injury
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9574168/
https://www.ncbi.nlm.nih.gov/pubmed/36253495
http://dx.doi.org/10.1038/s41598-022-22349-z
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