THE CRITICAL ROLE OF CYTOKINE DYSREGULATION IN ACUTE KIDNEY INJURY DEVELOPMENT IN PATIENTS WITH COVID-19

ABSTRACT

BACKGROUND AND AIMS: One of the complications described in critically ill patients in intensive care units with severe COVID-19 was acute kidney injury (AKI). The pathophysiology of AKI in patients with COVID-19 is multifactorial. In addition to the direct virulence of SARS-CoV-2 in renal cells, the tissue inflammation and local immune cell infiltration, cytokine storm, secondary infections and nephrotoxicity associated drugs may contribute to AKI [1]. Mounting evidence throughout the pandemic suggests that patients with severe COVID-19 may have a cytokine storm syndrome, one of the possible causes of AKI in these patients [2]. The present prospective cohort study analysed the correlation between circulating cytokine profile and estimated glomerular filtration rate (eGFR) in patients with COVID-19. METHOD: After signing the informed consent, patients positive for SARS-CoV- 2 infection (n = 74) had blood samples (n = 139) collected at hospital admission until the day of the outcome. ELISA measured the cytokines IL-10, IL-4, L-6, TNF- α and IFN-γ , and the eGFR was calculated by the CKD-EPI Cystatin C equation. Statistics description Continuous variables were checked for normality and presented as mean ± standard deviation or median and interquartile range. The association between continuous variables is shown in scatterplots, and a predicted response with 95% confidence interval (95% CI) is plotted using fractional polynomials. For linear correlations, we obtained P-values using Pearson's correlation coefficient. RESULTS: There is a more significant distribution of eGFR below 90 mL/min in the population studied, associated with older patients. Glomerular filtration rates were negatively correlated with age as expected (-0.60;P < 0.0001). Lower eGFR was correlated with levels of proinflammatory cytokines such as IL-6 (-0.33;P < .0007) and TNF- α (-0.21;P < .03);but without positive correlation with IL-10 (0.04;P < 0.68) or IFN-γ (-0.14;P < .16), even though higher IFN-γ levels have been linked to a worse prognosis in patients with severe COVID-19 [3]. Curiously, a positive correlation was observed between lower eGFR and IL-4 levels. CONCLUSION: These results demonstrate that a shift in the immune response profile, cytokines with a Th2 profile such as IL-4, and cytokines with systemic functions such as IL-6 and TNF-α can be related to renal failure. The elucidation of the potential pathophysiological mechanisms of AKI associated with COVID-19 as well as monitoring of cytokine levels can (a) help to identify patients with severe COVID-19 at risk of loss of renal function, (b) provide information on specific therapeutic strategies. (Figure Presented).