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- Bülow Anderberg, Sara
(author)
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Inflammatory aspects of acute kidney injury development during severe infections
- 2024
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Doctoral thesis (other academic/artistic)abstract
- Acute kidney injury is common in intensive care. In this setting sepsis, by definition a dysregulated inflammatory response secondary to infection, is the most common cause. Sepsis associated acute kidney injury is in turn linked to worse outcome. The syndrome is considered to be the result of multiple mechanisms elicited by the inflammatory response and not merely hypoperfusion. COVID-19 has become an additional cause of acute kidney injury in critically ill patients. The present thesis focused on investigating contributing aspects of the inflammatory response in regard to acute kidney injury development in sepsis and COVID-19.The innate immune response recognizes invading pathogens through preserved molecular structures. When detected small and short-acting immunomodulatory molecules, cytokines, are produced shaping the reaction. Neutrophils are quickly mobilized. They engage in degranulation and expulsion of extracellular traps aiming at eradicating pathogens but may in doing so cause collateral tissue damage. Neutrophils are proposed contributors to renal dysfunction during sepsis and COVID-19.We investigated the effect of hydrocortisone, a glucocorticoid, on renal function and neutrophil infiltration in an ovine sepsis model with associated renal impairment. The observed reduction in glomerular filtration and tubular sodium transport efficiency during sepsis was ameliorated. Neutrophil infiltration which was observed post mortem in renal tissue was not reduced by hydrocortisone.The progression of organ dysfunction and by extension also acute kidney injury during severe COVID-19 was early on considered caused by a hyperinflammatory state. We analysed plasma cytokine concentrations in patients admitted to intensive care because of respiratory failure secondary to COVID-19. Only a moderate increase of theses mediators was found. The majority of the cytokines analysed were in turn associated with acute kidney injury development.Human neutrophil lipocalin is a neutrophil granular protein. It was used to first evaluate neutrophil reactivity by measuring its concentration after ex vivo stimulation and second systemic activity by estimating its concentration in plasma. In turn the association with renal dysfunction in severe COVID-19 was explored. Increased concentrations in both instances were linked to a greater risk of developing severe acute kidney injury.Lastly, the effect of dexamethasone, another glucocorticoid, on AKI development and neutrophil extracellular markers including histones and myeloperoxidase-DNA in critical COVID-19 was investigated. Dexamethasone was associated with lower AKI incidence and reduced extracellular trap formation.
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| 2. |
- Venge, Per, et al.
(author)
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Plasma Biomarkers Associated to Outcome in Patients with Sars-Cov-2 Infection
- 2024
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In: Journal of Clinical and Laboratory Medicine. - : Sci Forschen, Inc.. - 2572-9578. ; 7:1
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Journal article (peer-reviewed)abstract
- Background: A serious consequence of respiratory infections with SARS-CoV-2 is Acute Kidney Injury (AKI). The aim of this study was to evaluate some novel biomarkers measured in plasma for their associations with the outcome of this infection as to AKI and mortality. Methods: Four different HNL (Human Neutrophil Lipocalin) assays were constructed using different antibody configurations, reflecting both neutrophil and epithelial cell activities. TK-1 (Thymidine kinase-1) was measured as a sign of cell destruction and proliferation. For comparison the plasma concentrations of NGAL (Neutrophil Gelatinase Associated Lipocalin), the cytokines IL-6, IL-8 and IFN-γ and of cystatin C, and procalcitonin were also measured. One hundred and three patients with severe respiratory failure admitted to the ICU were sampled for blood at admittance and at day three (n=67) after admittance. Results: Sixty-five percent of the patients developed AKI. The performance of the HNL assay 763/8F was most closely associated to outcome as to AKI and mortality with Area Under the Receiver Operating Characteristics Curve (AUC) of 0.87 and a sensitivity of 80% and a specificity of 88% in COVID-19 patients with and without severe AKI (p<0.0001). TK-1 was significantly related to the development of AKI (p=0.01) and the three cytokines were related to mortality (p=0.004-p<0.001). Conclusion: The HNL variant 763/8F and TK-1 are novel biomarkers that might become useful and novel tools in the management of COVID-19 patients, but likely also in other patients affected by AKI.
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