TY - JOUR
T1 - Complement levels at admission reflecting progression to severe acute kidney injury (AKI) in Coronavirus Disease 2019 (COVID-19)
T2 - A multicenter prospective cohort study
AU - Henry, Brandon M
AU - Sinkovits, György
AU - Szergyuk, Ivan
AU - de Oliveira, Maria Helena Santos
AU - Lippi, Giuseppe
AU - Benoit, Justin L
AU - Favaloro, Emmanuel J
AU - Pode-Shakked, Naomi
AU - Benoit, Stefanie W
AU - Cooper, David S
AU - Müller, Veronika
AU - Iványi, Zsolt
AU - Gál, János
AU - Réti, Marienn
AU - Gopcsa, László
AU - Reményi, Péter
AU - Szathmáry, Beáta
AU - Lakatos, Botond
AU - Szlávik, János
AU - Bobek, Ilona
AU - Prohászka, Zita Z
AU - Förhécz, Zsolt
AU - Csuka, Dorottya
AU - Hurler, Lisa
AU - Kajdácsi, Erika
AU - Cervenak, László
AU - Mező, Blanka
AU - Kiszel, Petra
AU - Masszi, Tamás
AU - Vályi-Nagy, István
AU - Prohászka, Zoltán
N1 - Publisher Copyright:
Copyright © 2022 Henry, Sinkovits, Szergyuk, de Oliveira, Lippi, Benoit, Favaloro, Pode-Shakked, Benoit, Cooper, Müller, Iványi, Gál, Réti, Gopcsa, Reményi, Szathmáry, Lakatos, Szlávik, Bobek, Prohászka, Förhécz, Csuka, Hurler, Kajdácsi, Cervenak, Mező, Kiszel, Masszi, Vályi-Nagy and Prohászka.
PY - 2022/4/29
Y1 - 2022/4/29
N2 - Background: Dysregulation of complement system is thought to be a major player in development of multi-organ damage and adverse outcomes in patients with coronavirus disease 2019 (COVID-19). This study aimed to examine associations between complement system activity and development of severe acute kidney injury (AKI) among hospitalized COVID-19 patients. Materials and Methods: In this multicenter, international study, complement as well as inflammatory and thrombotic parameters were analyzed in COVID-19 patients requiring hospitalization at one US and two Hungarian centers. The primary endpoint was development of severe AKI defined by KDIGO stage 2+3 criteria, while the secondary endpoint was need for renal replacement therapy (RRT). Complement markers with significant associations with endpoints were then correlated with a panel of inflammatory and thrombotic biomarkers and assessed for independent association with outcome measures using logistic regression. Results: A total of 131 hospitalized COVID-19 patients (median age 66 [IQR, 54–75] years; 54.2% males) were enrolled, 33 from the US, and 98 from Hungary. There was a greater prevalence of complement over-activation and consumption in those who developed severe AKI and need for RRT during hospitalization. C3a/C3 ratio was increased in groups developing severe AKI (3.29 vs. 1.71; p < 0.001) and requiring RRT (3.42 vs. 1.79; p < 0.001) in each cohort. Decrease in alternative and classical pathway activity, and consumption of C4 below reference range, as well as elevation of complement activation marker C3a above the normal was more common in patients progressing to severe AKI. In the Hungarian cohort, each standard deviation increase in C3a (SD = 210.1) was independently associated with 89.7% increased odds of developing severe AKI (95% CI, 7.6–234.5%). Complement was extensively correlated with an array of inflammatory biomarkers and a prothrombotic state. Conclusion: Consumption and dysregulation of complement system is associated with development of severe AKI in COVID-19 patients and could represent a promising therapeutic target for reducing thrombotic microangiopathy in SARS-CoV-2 infection.
AB - Background: Dysregulation of complement system is thought to be a major player in development of multi-organ damage and adverse outcomes in patients with coronavirus disease 2019 (COVID-19). This study aimed to examine associations between complement system activity and development of severe acute kidney injury (AKI) among hospitalized COVID-19 patients. Materials and Methods: In this multicenter, international study, complement as well as inflammatory and thrombotic parameters were analyzed in COVID-19 patients requiring hospitalization at one US and two Hungarian centers. The primary endpoint was development of severe AKI defined by KDIGO stage 2+3 criteria, while the secondary endpoint was need for renal replacement therapy (RRT). Complement markers with significant associations with endpoints were then correlated with a panel of inflammatory and thrombotic biomarkers and assessed for independent association with outcome measures using logistic regression. Results: A total of 131 hospitalized COVID-19 patients (median age 66 [IQR, 54–75] years; 54.2% males) were enrolled, 33 from the US, and 98 from Hungary. There was a greater prevalence of complement over-activation and consumption in those who developed severe AKI and need for RRT during hospitalization. C3a/C3 ratio was increased in groups developing severe AKI (3.29 vs. 1.71; p < 0.001) and requiring RRT (3.42 vs. 1.79; p < 0.001) in each cohort. Decrease in alternative and classical pathway activity, and consumption of C4 below reference range, as well as elevation of complement activation marker C3a above the normal was more common in patients progressing to severe AKI. In the Hungarian cohort, each standard deviation increase in C3a (SD = 210.1) was independently associated with 89.7% increased odds of developing severe AKI (95% CI, 7.6–234.5%). Complement was extensively correlated with an array of inflammatory biomarkers and a prothrombotic state. Conclusion: Consumption and dysregulation of complement system is associated with development of severe AKI in COVID-19 patients and could represent a promising therapeutic target for reducing thrombotic microangiopathy in SARS-CoV-2 infection.
KW - acute kidney injury
KW - complement system
KW - coronavirus disease 2019
KW - renal replacement therapy (RRT)
KW - SARS-CoV-2
UR - http://www.scopus.com/inward/record.url?scp=85130293780&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85130293780&partnerID=8YFLogxK
U2 - 10.3389/fmed.2022.796109
DO - 10.3389/fmed.2022.796109
M3 - Article
C2 - 35572977
SN - 2296-858X
VL - 9
SP - 1
EP - 12
JO - Frontiers in medicine
JF - Frontiers in medicine
M1 - 796109
ER -
