Circulating Soluble Urokinase Plasminogen Activator Receptor as a Predictive Indicator for COVID-19-Associated Acute Kidney Injury and Mortality: Clinical and Bioinformatics Analysis.

Urokinase receptors regulate the interplay between inflammation, immunity, and blood clotting. The soluble urokinase plasminogen activator system is an immunologic regulator affecting endothelial function and its related receptor; the soluble urokinase plasminogen activator receptor (suPAR) has been reported to impact kidney injury. This work aims to measure serum levels of suPAR in COVID-19 patients and correlate the measurements with variable clinicolaboratory parameters and patient outcomes. In this prospective cohort study, 150 COVID-19 patients and 50 controls were included. The circulating suPAR levels were quantified by Enzyme-linked immunosorbent assay (ELISA). Routine COVID-19 laboratory assessments, including CBC, CRP, LDH, serum creatinine, and estimated glomerular filtration rates, were performed. The need for oxygen therapy, CO-RAD score, and survival rates was assessed. Bioinformatic analysis and molecular docking were run to explore the urokinase receptor structure/function and to characterize molecules as potential anti-suPAR therapeutic targets, respectively. We found higher circulating suPAR levels in COVID-19 patients vs. controls (p < 0.001). Circulating suPAR levels positively correlated with COVID-19 severity, the need for O2 therapy, the total leukocytes count, and the neutrophils to lymphocyte ratio, while they were negatively correlated with the O2 saturation level, albumin, blood calcium, lymphocytic count, and GFR. In addition, the suPAR levels were associated with poor prognostic outcomes such as a high incidence of acute kidney injury (AKI) and mortality rate. Kaplan-Meier curves showed a lower survival rate with higher suPAR levels. The logistic regression analysis confirmed the significant association of suPAR levels with the occurrence of AKI related to COVID-19 and with increased mortality probability within three months of COVID-19 follow-up. Some compounds that can act similarly to uPAR were discovered and tested by molecular docking to identify the possible ligand-protein interactions. In conclusion, higher circulating suPAR levels were associated with COVID-19 severity and could be considered a putative predictor of AKI development and mortality.

Adherence to hemodialysis and medical regimens among patients with end-stage renal disease during COVID-19 pandemic: a cross-sectional study.

BACKGROUND: Adherence of patients with End-Stage Renal Disease (ESRD) to Hemodialysis (HD), prescribed medications, diet and fluid restrictions is essential to get the desirable outcome and prevent complications. During COVID-19 pandemic, ESRD patients became more concerned with attending the HD sessions and following the protective measures because of the potential for increased susceptibility to COVID-19. The aim of this study was to evaluate the impact of the pandemic on patients' adherence to HD and medical regimens. METHODS: Two hundred five ESRD patients on HD were interviewed with the ESRD Adherence Questionnaire (ESRD-AQ) and the Fear-of-COVID-19 Scale (FCV-19S). Clinical and laboratory correlates of adherence were retrieved from patients' records. RESULTS: Self-reported adherence to HD showed that 19.5% were not adherent to HD during the pandemic compared to 11.7% before the pandemic (p < 0.001), with a significant agreement with the actual attendance of HD sessions (Kappa = 0.733, p < 0.001). Twenty-five patients (12.2%) had a history of COVID-19. The FCV-19S had a mean score of 18.8 and showed significant positive correlations with the pre-dialysis phosphorus and potassium. Multivariate analysis showed that the main predictors of non-adherence were the history of COVID-19, understanding and perception scores, and the Fear-of-COVID score. CONCLUSIONS: The COVID-19 pandemic adversely affected the adherence of ESRD patients to HD and medical regimen. Strategies to mitigate patients' fears of COVID-19 and improve their understanding and perceptions of adherence to HD and medical regimen should be adopted in HD centers during the pandemic.