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Urinary C3 levels associated with sepsis and acute kidney injury—A pilot study

Acute kidney injury (AKI) is an abrupt deterioration of renal function often caused by severe clinical disease such as sepsis, and patients require intensive care. Acute-phase parameters for systemic inflammation are well established and used in routine clinical diagnosis, but no such parameters are...

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Autores principales: Pajenda, Sahra, Zawedde, Florence, Kapps, Sebastian, Wagner, Ludwig, Schmidt, Alice, Winnicki, Wolfgang, O’Connell, David, Gerges, Daniela
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8589214/
https://www.ncbi.nlm.nih.gov/pubmed/34767613
http://dx.doi.org/10.1371/journal.pone.0259777
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author Pajenda, Sahra
Zawedde, Florence
Kapps, Sebastian
Wagner, Ludwig
Schmidt, Alice
Winnicki, Wolfgang
O’Connell, David
Gerges, Daniela
author_facet Pajenda, Sahra
Zawedde, Florence
Kapps, Sebastian
Wagner, Ludwig
Schmidt, Alice
Winnicki, Wolfgang
O’Connell, David
Gerges, Daniela
author_sort Pajenda, Sahra
collection PubMed
description Acute kidney injury (AKI) is an abrupt deterioration of renal function often caused by severe clinical disease such as sepsis, and patients require intensive care. Acute-phase parameters for systemic inflammation are well established and used in routine clinical diagnosis, but no such parameters are known for AKI and inflammation at the local site of tissue damage, namely the nephron. Therefore, we sought to investigate complement factors C3a/C3 in urine and urinary sediment cells. After the development of a C3a/C3-specific mouse monoclonal antibody (3F7E2), urine excretion from ICU sepsis patients was examined by dot blot and immunoblotting. This C3a/C3 ELISA and a C3a ELISA were used to obtain quantitative data over 24 hours for 6 consecutive days. Urine sediment cells were analyzed for topology of expression. Patients with severe infections (n = 85) showed peak levels of C3a/C3 on the second day of ICU treatment. The majority (n = 59) showed C3a/C3 levels above 20 μg/ml at least once in the first 6 days after admission. C3a was detectable on all 6 days. Peak C3a/C3 levels correlated negatively with peak C-reactive protein (CRP) levels. No relationship was found between peak C3a/C3 with peak leukocyte count, age, or AKI stage. Analysis of urine sediment cells identified C3a/C3-producing epithelial cells with reticular staining patterns and cells with large-granular staining. Opsonized bacteria were detected in patients with urinary tract infections. In critically ill sepsis patients with AKI, urinary C3a/C3 inversely correlated with serum CRP. Whether urinary C3a/C3 has a protective function through autophagy, as previously shown for cisplatin exposure, or is a by-product of sepsis caused by pathogenic stimuli to the kidney must remain open in this study. However, our data suggest that C3a/C3 may function as an inverse acute-phase parameter that originates in the kidney and is detectable in urine.
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spelling pubmed-85892142021-11-13 Urinary C3 levels associated with sepsis and acute kidney injury—A pilot study Pajenda, Sahra Zawedde, Florence Kapps, Sebastian Wagner, Ludwig Schmidt, Alice Winnicki, Wolfgang O’Connell, David Gerges, Daniela PLoS One Research Article Acute kidney injury (AKI) is an abrupt deterioration of renal function often caused by severe clinical disease such as sepsis, and patients require intensive care. Acute-phase parameters for systemic inflammation are well established and used in routine clinical diagnosis, but no such parameters are known for AKI and inflammation at the local site of tissue damage, namely the nephron. Therefore, we sought to investigate complement factors C3a/C3 in urine and urinary sediment cells. After the development of a C3a/C3-specific mouse monoclonal antibody (3F7E2), urine excretion from ICU sepsis patients was examined by dot blot and immunoblotting. This C3a/C3 ELISA and a C3a ELISA were used to obtain quantitative data over 24 hours for 6 consecutive days. Urine sediment cells were analyzed for topology of expression. Patients with severe infections (n = 85) showed peak levels of C3a/C3 on the second day of ICU treatment. The majority (n = 59) showed C3a/C3 levels above 20 μg/ml at least once in the first 6 days after admission. C3a was detectable on all 6 days. Peak C3a/C3 levels correlated negatively with peak C-reactive protein (CRP) levels. No relationship was found between peak C3a/C3 with peak leukocyte count, age, or AKI stage. Analysis of urine sediment cells identified C3a/C3-producing epithelial cells with reticular staining patterns and cells with large-granular staining. Opsonized bacteria were detected in patients with urinary tract infections. In critically ill sepsis patients with AKI, urinary C3a/C3 inversely correlated with serum CRP. Whether urinary C3a/C3 has a protective function through autophagy, as previously shown for cisplatin exposure, or is a by-product of sepsis caused by pathogenic stimuli to the kidney must remain open in this study. However, our data suggest that C3a/C3 may function as an inverse acute-phase parameter that originates in the kidney and is detectable in urine. Public Library of Science 2021-11-12 /pmc/articles/PMC8589214/ /pubmed/34767613 http://dx.doi.org/10.1371/journal.pone.0259777 Text en © 2021 Pajenda et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Pajenda, Sahra
Zawedde, Florence
Kapps, Sebastian
Wagner, Ludwig
Schmidt, Alice
Winnicki, Wolfgang
O’Connell, David
Gerges, Daniela
Urinary C3 levels associated with sepsis and acute kidney injury—A pilot study
title Urinary C3 levels associated with sepsis and acute kidney injury—A pilot study
title_full Urinary C3 levels associated with sepsis and acute kidney injury—A pilot study
title_fullStr Urinary C3 levels associated with sepsis and acute kidney injury—A pilot study
title_full_unstemmed Urinary C3 levels associated with sepsis and acute kidney injury—A pilot study
title_short Urinary C3 levels associated with sepsis and acute kidney injury—A pilot study
title_sort urinary c3 levels associated with sepsis and acute kidney injury—a pilot study
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8589214/
https://www.ncbi.nlm.nih.gov/pubmed/34767613
http://dx.doi.org/10.1371/journal.pone.0259777
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