TY - JOUR
T1 - Host Response Protein Biomarkers Indicative of Persistent Acute Kidney Injury in Critically Ill COVID-19 Patients
AU - Steenvoorden, Thei S.
AU - de Kruijf, Koen C.
AU - Appelman, Brent
AU - Moggre, Bas
AU - Bos, Lieuwe D.J.
AU - Vlaar, Alexander P.J.
AU - Douma, Reneé A.
AU - Uhel, Fabrice
AU - Kers, Jesper
AU - Oppelaar, Jetta J.
AU - van Vught, Lonneke A.
AU - Beudel, Martijn
AU - Elbers, Paul W.G.
AU - Joost Wiersinga, W.
AU - van der Poll, Tom
AU - Vogt, Liffert
AU - Peters-Sengers, Hessel
AU - van de Beek, Diederik
AU - de Bruin, Sanne
AU - Rusch, Daisy
AU - Simsek, Suat
AU - Brinkman, Kees
AU - van den Oever, Niels Gritters
AU - van den Bergh, Joop
AU - Moeniralam, Hamza
AU - Bokhizzou, N.
AU - de Kruif, Martijn
AU - Leavis, Helen
N1 - Publisher Copyright:
Copyright © 2025 The Authors.
PY - 2025/3/13
Y1 - 2025/3/13
N2 - IMPORTANCE: Sepsis-related host-response anomalies contribute to acute kidney injury (AKI) duration. Data on the host-response specific to COVID-19associated AKI (COVID-AKI) in critically ill patients is limited. OBJECTIVES: We postulated that persistent COVID-AKI (> 48hr) differs in host response from transient (< 48hr) or no COVID-AKI. DESIGN, SETTING, AND PARTICIPANTS: This prospective biomarker study observed patients with severe acute respiratory syndrome coronavirus 2 infection, without chronic kidney disease, in three ICUs from March 2020 to July 2020. AKI was assessed by hourly urine output and daily plasma creatinine. MAIN OUTCOMES AND MEASURES: Luminex and enzyme-linked immunosorbent assay were used to analyze 48 plasma protein biomarkers across six pathophysiological domains, which were tested with mixed-effects models. RESULTS: Of 177 included patients, 106 (59.9%) had AKI within the first 48 hours of admission, of whom 76 (71.7%) had persistent AKI and 30 (28.3%) transient AKI. Those with persistent AKI often had obesity, hypertension, and a higher Sequential Organ Failure Assessment score due to the renal component. Longitudinal analyses revealed that seven proteins were elevated in persistent AKI compared with no AKI. These were related to inflammation (triggering receptor expressed on myeloid cells 1, p < 0.001; tumor necrosis factor receptor 1, p < 0.001; procalcitonin, p = 0.001), complement activation (mannan-binding lectin serine protease-2, p = 0.001), kidney dysfunction (cystatin C, p < 0.001; neutrophil gelatinase-associated lipocalin, p < 0.001), and lung dysfunction (Clara cell secretory protein 16, p < 0.001). AKI (duration) was not associated with differences in the cytokine signaling, endothelial cell activation, or coagulation domains. CONCLUSIONS AND RELEVANCE: In contrast with sepsis-associated AKI, primarily inflammation-related biomarker levels correlated with COVID-AKI persistence. This study offers insights into COVID-AKI and may guide approaches to mitigate its persistence.
AB - IMPORTANCE: Sepsis-related host-response anomalies contribute to acute kidney injury (AKI) duration. Data on the host-response specific to COVID-19associated AKI (COVID-AKI) in critically ill patients is limited. OBJECTIVES: We postulated that persistent COVID-AKI (> 48hr) differs in host response from transient (< 48hr) or no COVID-AKI. DESIGN, SETTING, AND PARTICIPANTS: This prospective biomarker study observed patients with severe acute respiratory syndrome coronavirus 2 infection, without chronic kidney disease, in three ICUs from March 2020 to July 2020. AKI was assessed by hourly urine output and daily plasma creatinine. MAIN OUTCOMES AND MEASURES: Luminex and enzyme-linked immunosorbent assay were used to analyze 48 plasma protein biomarkers across six pathophysiological domains, which were tested with mixed-effects models. RESULTS: Of 177 included patients, 106 (59.9%) had AKI within the first 48 hours of admission, of whom 76 (71.7%) had persistent AKI and 30 (28.3%) transient AKI. Those with persistent AKI often had obesity, hypertension, and a higher Sequential Organ Failure Assessment score due to the renal component. Longitudinal analyses revealed that seven proteins were elevated in persistent AKI compared with no AKI. These were related to inflammation (triggering receptor expressed on myeloid cells 1, p < 0.001; tumor necrosis factor receptor 1, p < 0.001; procalcitonin, p = 0.001), complement activation (mannan-binding lectin serine protease-2, p = 0.001), kidney dysfunction (cystatin C, p < 0.001; neutrophil gelatinase-associated lipocalin, p < 0.001), and lung dysfunction (Clara cell secretory protein 16, p < 0.001). AKI (duration) was not associated with differences in the cytokine signaling, endothelial cell activation, or coagulation domains. CONCLUSIONS AND RELEVANCE: In contrast with sepsis-associated AKI, primarily inflammation-related biomarker levels correlated with COVID-AKI persistence. This study offers insights into COVID-AKI and may guide approaches to mitigate its persistence.
KW - acute kidney injury
KW - COVID-19
KW - host response
KW - intensive care unit
UR - https://www.scopus.com/pages/publications/105001641171
U2 - 10.1097/CCE.0000000000001222
DO - 10.1097/CCE.0000000000001222
M3 - Article
AN - SCOPUS:105001641171
SN - 2639-8028
VL - 7
JO - Critical care explorations
JF - Critical care explorations
IS - 3
ER -