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https://www.arca.fiocruz.br/handle/icict/56769
ACUTE KIDNEY INJURY ASSOCIATED TO COVID-19 LEADS TO A STRONG UNBALANCE OF CIRCULANT IMMUNE MEDIATORS
Author
Medeiros, Thalia
Guimarães, Gabriel Macedo Costa
Carvalho, Fabiana Rabe
Alves, Lilian Santos
Faustino, Renan
Azevedo, Ana Carolina Campi
Pascoal, Vanessa Peruhype Magalhães
Carvalho, Andréa Teixeira de
Gomes, Matheus de Souza
Amaral, Laurence Rodrigues do
Martins Filho, Olindo Assis
Lugon, Jocemir Ronaldo
Almeida, Jorge Reis
Silva, Andrea Alice
Guimarães, Gabriel Macedo Costa
Carvalho, Fabiana Rabe
Alves, Lilian Santos
Faustino, Renan
Azevedo, Ana Carolina Campi
Pascoal, Vanessa Peruhype Magalhães
Carvalho, Andréa Teixeira de
Gomes, Matheus de Souza
Amaral, Laurence Rodrigues do
Martins Filho, Olindo Assis
Lugon, Jocemir Ronaldo
Almeida, Jorge Reis
Silva, Andrea Alice
Affilliation
Multiuser Laboratory for Research Support in Nephrology and Medical Sciences. Hospital Universitario Antonio Pedro. Faculty of Medicine. Universidade Federal Fluminense. Niteroi, RJ, Brazil/ Department of Pathology. Faculty of Medicine. Universidade Federal Fluminense. Niterói, RJ, Brazil.
Multiuser Laboratory for Research Support in Nephrology and Medical Sciences. Hospital Universitario Antonio Pedro. Faculty of Medicine. Universidade Federal Fluminense. Niteroi, RJ, Brazil
Multiuser Laboratory for Research Support in Nephrology and Medical Sciences. Hospital Universitario Antonio Pedro. Faculty of Medicine. Universidade Federal Fluminense. Niteroi, RJ, Brazil
Multiuser Laboratory for Research Support in Nephrology and Medical Sciences. Hospital Universitario Antonio Pedro. Faculty of Medicine. Universidade Federal Fluminense. Niteroi, RJ, Brazil
Multiuser Laboratory for Research Support in Nephrology and Medical Sciences. Hospital Universitario Antonio Pedro. Faculty of Medicine. Universidade Federal Fluminense. Niteroi, RJ, Brazil
Fundação Oswaldo Cruz. Instituto René Rachou. Belo Horizonte, Minas Gerais, Brazil.
Fundação Oswaldo Cruz. Instituto René Rachou. Belo Horizonte, Minas Gerais, Brazil.
Fundação Oswaldo Cruz. Instituto René Rachou. Belo Horizonte, Minas Gerais, Brazil.
Laboratory of Bioinformatics and Molecular Analysis. Federal University of Uberlandia. Patos de Minas, MG, Brazil.
Laboratory of Bioinformatics and Molecular Analysis. Federal University of Uberlandia. Patos de Minas, MG, Brazil.
Fundação Oswaldo Cruz. Instituto René Rachou. Belo Horizonte, Minas Gerais, Brazil.
Multiuser Laboratory for Research Support in Nephrology and Medical Sciences. Hospital Universitario Antonio Pedro. Faculty of Medicine. Universidade Federal Fluminense. Niteroi, RJ, Brazil/Department of Clinical Medicine – Nephrology. Faculty of Medicine. Universidade Federal Fluminense. Niteroi, RJ, Brazil.
Multiuser Laboratory for Research Support in Nephrology and Medical Sciences. Hospital Universitario Antonio Pedro. Faculty of Medicine. Universidade Federal Fluminense. Niteroi, RJ, Brazil
Multiuser Laboratory for Research Support in Nephrology and Medical Sciences. Hospital Universitario Antonio Pedro. Faculty of Medicine. Universidade Federal Fluminense. Niteroi, RJ, Brazil/ Department of Pathology. Faculty of Medicine. Universidade Federal Fluminense. Niterói, RJ, Brazil.
Multiuser Laboratory for Research Support in Nephrology and Medical Sciences. Hospital Universitario Antonio Pedro. Faculty of Medicine. Universidade Federal Fluminense. Niteroi, RJ, Brazil
Multiuser Laboratory for Research Support in Nephrology and Medical Sciences. Hospital Universitario Antonio Pedro. Faculty of Medicine. Universidade Federal Fluminense. Niteroi, RJ, Brazil
Multiuser Laboratory for Research Support in Nephrology and Medical Sciences. Hospital Universitario Antonio Pedro. Faculty of Medicine. Universidade Federal Fluminense. Niteroi, RJ, Brazil
Multiuser Laboratory for Research Support in Nephrology and Medical Sciences. Hospital Universitario Antonio Pedro. Faculty of Medicine. Universidade Federal Fluminense. Niteroi, RJ, Brazil
Fundação Oswaldo Cruz. Instituto René Rachou. Belo Horizonte, Minas Gerais, Brazil.
Fundação Oswaldo Cruz. Instituto René Rachou. Belo Horizonte, Minas Gerais, Brazil.
Fundação Oswaldo Cruz. Instituto René Rachou. Belo Horizonte, Minas Gerais, Brazil.
Laboratory of Bioinformatics and Molecular Analysis. Federal University of Uberlandia. Patos de Minas, MG, Brazil.
Laboratory of Bioinformatics and Molecular Analysis. Federal University of Uberlandia. Patos de Minas, MG, Brazil.
Fundação Oswaldo Cruz. Instituto René Rachou. Belo Horizonte, Minas Gerais, Brazil.
Multiuser Laboratory for Research Support in Nephrology and Medical Sciences. Hospital Universitario Antonio Pedro. Faculty of Medicine. Universidade Federal Fluminense. Niteroi, RJ, Brazil/Department of Clinical Medicine – Nephrology. Faculty of Medicine. Universidade Federal Fluminense. Niteroi, RJ, Brazil.
Multiuser Laboratory for Research Support in Nephrology and Medical Sciences. Hospital Universitario Antonio Pedro. Faculty of Medicine. Universidade Federal Fluminense. Niteroi, RJ, Brazil
Multiuser Laboratory for Research Support in Nephrology and Medical Sciences. Hospital Universitario Antonio Pedro. Faculty of Medicine. Universidade Federal Fluminense. Niteroi, RJ, Brazil/ Department of Pathology. Faculty of Medicine. Universidade Federal Fluminense. Niterói, RJ, Brazil.
Abstract
Background: Severe cases of coronavirus disease 2019 (COVID-19) have increased risk for acute kidney injury (AKI). The exacerbation of the immune response seems to contribute to AKI development, but the immunopathological process is not completely understood.
Objectives: To analyze levels of circulant immune mediators in COVID-19 patients evolving with or without AKI. We have also investigated possible associations of these mediators with viral load and clinical outcomes.
Methods: This is a longitudinal study performed with hospitalized patients with moderate to severe COVID-19. Serum levels of 27 immune mediators were measured by a multiplex immunoassay. Data were analyzed at two timepoints during the follow-up: within the first 13 days of the disease onset (early sample) and from the 14th day to death or hospital discharge (follow-up sample).
Results: We studied 82 COVID-19 patients (59.5 ± 17.5 years, 54.9% male). Of these, 34 (41.5%) developed AKI. These patients presented higher SARS-CoV-2 viral load (P = 0.03), higher frequency of diabetes (P = 0.01) and death (P = 0.0004). Overall, AKI patients presented significantly higher and sustained levels (P < 0.05) of CCL-2, CCL-3, CCL-4, CXCL-8, CXCL-10, IFN-γ, IL-2, IL-6, TNF-α, IL-1Ra, IL-10 and VEGF. Importantly, higher levels of CCL-2, CXCL-10, IL-2, TNF-α, IL-10, FGFb, and VEGF were observed in AKI patients independently of death. ROC curves demonstrated that early alterations in CCL-2, CXCL-8, CXCL-10, IFN-γ, IL-6, IL-1Ra and IL-10 show a good predictive value regarding AKI development. Lastly, immune mediators were significantly associated with each other and with SARS-CoV-2 viral load in AKI patients.
Conclusions: COVID-19 associated AKI is accompanied by substantial alterations in circulant levels of immune mediators, which could significantly contribute to the establishment of kidney injury.
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