Role of Tissue Inhibitor of Metalloproteinases-2 and Insulin Like Growth Factor Binding Protein 7 for Early Recognition of Acute Kidney Injury in Critically Ill COVID-19 Patients (preprint)

Background: A high proportion of critically ill patients with COVID-19 develop acute kidney injury (AKI) and die. Early recognition of subclinical AKI could contribute to AKI prevention. Therefore, this study was aimed at exploring the role of the urinary biomarkers NGAL and [TIMP-2]•[IGFBP7] for early detection of AKI in this population. Methods: : This prospective, longitudinal cohort study included critically ill COVID-19 patients without AKI at study entry. Urine samples were collected on admission to critical care areas for determination of NGAL and [TIMP-2]•[IGFBP7] concentrations. Demographic information, comorbidities, clinical and laboratory data were recorded. The study outcomes were development of AKI and mortality during hospitalization. Comparisons of individuals who developed AKI during hospitalization vs. those without AKI were made using chi-squared test for categorical variables and Mann-Whitney U for continuous variables. Urinary biomarkers and their cutoff values were selected based on the highest sensitivity, specificity and area under the receiver-operating characteristics curve with 95% confidence intervals for prediction of AKI. Selected biomarkers and cutoffs were used in the Kaplan-Meier survival analyses for the time to AKI. Logistic regression analysis was used to identify the association between relevant covariates with AKI and mortality. For all analyses, two-sided P values £0.05 were considered statistically significant. Results: : Of the 51 individuals studied, 25 developed AKI during hospitalization (49%). The risk factors for AKI were male gender (HR=7.57, 95% CI: 1.28-44.8; p=0.026) and [TIMP-2]•[IGFBP7] ³ 0.2 (ng/ml) 2 /1000 (HR=7.23 , 95% CI: 0.99-52.4; p=0.050). Mortality during hospitalization was significantly higher in the group with AKI than in the group without AKI (p=0.004). Persistent AKI was a risk factor for mortality (HR=7.42, 95% CI: 1.04-53.04; p=0.046). Conclusions: : The combination of [TIMP-2]•[IGFBP7], together with clinical information, were useful for identification of subclinical AKI in critically ill COVID-19 patients. The role of additional biomarkers and their possible combinations for detection of AKI in critically ill COVID-19 patients remains to be explored in large clinical trials.

High-flow nasal cannula therapy for hypoxemic respiratory failure in patients with COVID-19 (preprint)

Purpose High-flow nasal cannula (HFNC) therapy in patients with hypoxemic respiratory failure due to COVID-19 is poorly understood and remains controversial.Methods We designed a prospective observational study of a large cohort of patients with COVID-19-related hypoxaemic respiratory failure at the Temporary COVID-19 Hospital in Mexico City. The primary outcome was the success rate of HFNC to prevent the progression to invasive mechanical ventilation (IMV). We also evaluated the risk factors associated with HFNC success or failure.Results This study included 378 patients who were admitted to the Temporary COVID-19 Hospital with a confirmed diagnosis of COVID-19 and hypoxemic respiratory failure. HFNC therapy effectively prevented IMV in 71.4% of patients (n = 270; 95% confidence interval [CI] 66.6–75.8%). Factors that were significantly different between patients who were only treated with HFNC therapy and those who progressed to IMV included age, the presence of hypertension, and the Charlson comorbidity index. Predictors of therapy failure included the CALL score at admission (adjusted hazard ratio [HR] 1.27; 95% CI 1.09–1.47; p < 0.01), Rox index at 1 hour (adjusted HR 0.82; 95% CI 0.7–0.96; p = 0.02), and no prior treatment with steroids (adjusted HR 0.34; 95% CI 0.19–0.62; p < 0.0001). Overall, therapy was significantly associated with a lower intensive care unit admission rate (7.0% vs 96.3%) and length of hospital stay (15.0 vs 26.5 days).Conclusions Treating patients with HFNC therapy at admission was effective and prevented the worsening of symptoms in some patients with COVID-19.

Acute kidney injury in patients with severe COVID-19 in Mexico (preprint)

Introduction: Some patients with COVID-19 pneumonia present systemic disease involving multiple systems. There is limited information about the clinical characteristics and events leading to acute kidney injury (AKI). We described the factors associated with the development of AKI and explored the relation of AKI and mortality in Mexican population with severe COVID-19. Methods: We retrospectively reviewed the medical records of individuals with severe pneumonia caused by SARS-CoV-2 hospitalized at the largest third-level reference institution for COVID-19 care in Mexico between March and April 2020. Demographic information, comorbidities, clinical and laboratory data, dates of mechanical ventilation and hospitalization, mechanical-ventilator settings and use of vasoactive drugs were recorded. Results: Of 99 patients studied, 58 developed AKI (58.6%). The group with AKI had higher body mass index (p=0.0003) and frequency of obesity (p=0.001); a higher requirement of invasive mechanical ventilation (p=0.008) and vasoactive drugs (p=0.004); greater levels of serum creatinine (p<0.001) and D-dimer on admission (p<0.001); and lower lymphocyte counts (p=0.001) than the non-AKI group. The multivariate analysis indicated that risk factors for AKI were obesity (adjusted hazard ratio (HR)=2.71, 95% confidence interval (CI)=1.33-5.51, p=0.005); higher serum creatinine (HR=1.44, CI=1.02-2.02, p=0.035) and D-dimer levels on admission (HR=1.14, CI=1.06-1.23, p<0.001). In-hospital mortality was higher in the AKI group than in the non-AKI group (65.5% vs. 14.6%; p=0.001). Conclusions: AKI was common in our cohort of patients with severe COVID-19 and it was associated with mortality. The risk factors for AKI were obesity, elevated creatinine levels and higher D-dimer levels on admission. Key words: Acute kidney injury; AKI; acute renal failure; COVID-19; SARS-CoV-2.