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:	Sahra Pajenda, Florence Zawedde, Sebastian Kapps, Ludwig Wagner, Alice Schmidt, Wolfgang Winnicki, David O’Connell, Daniela Gerges
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/5c9531bd07f640dba23212dace453c27
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spelling	oai:doaj.org-article:5c9531bd07f640dba23212dace453c272021-11-25T06:10:59ZUrinary C3 levels associated with sepsis and acute kidney injury—A pilot study1932-6203https://doaj.org/article/5c9531bd07f640dba23212dace453c272021-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8589214/?tool=EBIhttps://doaj.org/toc/1932-6203Acute 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.Sahra PajendaFlorence ZaweddeSebastian KappsLudwig WagnerAlice SchmidtWolfgang WinnickiDavid O’ConnellDaniela GergesPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 16, Iss 11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Sahra Pajenda Florence Zawedde Sebastian Kapps Ludwig Wagner Alice Schmidt Wolfgang Winnicki David O’Connell Daniela Gerges Urinary C3 levels associated with sepsis and acute kidney injury—A pilot study
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.
format	article
author	Sahra Pajenda Florence Zawedde Sebastian Kapps Ludwig Wagner Alice Schmidt Wolfgang Winnicki David O’Connell Daniela Gerges
author_facet	Sahra Pajenda Florence Zawedde Sebastian Kapps Ludwig Wagner Alice Schmidt Wolfgang Winnicki David O’Connell Daniela Gerges
author_sort	Sahra Pajenda
title	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_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_sort	urinary c3 levels associated with sepsis and acute kidney injury—a pilot study
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/5c9531bd07f640dba23212dace453c27
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Urinary C3 levels associated with sepsis and acute kidney injury—A pilot study

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