Fluid Status Assessment in Critically Ill Patients with COVID-19: A Retrospective Cohort Study.

Fluid status (FS) is a diagnostic challenge in critically ill patients with COVID-19. Here, we compared parameters related to FS derived from cumulative fluid balance (CFB), bioelectrical impedance analysis (BIA) and venous congestion assessed by ultrasound (VExUS) to predict mortality. We retrospectively reviewed the medical records of individuals with severe pneumonia due to COVID-19 between July and November 2021 in a single center. Comorbidities, demographic, clinical and laboratory data as well as results from CFB, BIA and VExUS measurements were collected on admission and weekly afterwards for two consecutive evaluations. Seventy-nine patients were included, of which eighteen (14.2%) died. Abnormalities of FS were only identified by BIA. Extracellular water/total body water ratio (ECW/TBW) > 0.394 (overhydrated) by BIA was a good predictor of mortality (AUC = 0.78, 95% CI: 0.067-0.89). Mortality risk was higher in overhydrated patients (OR: 6.2, 95% CI: 1.2-32.6, p = 0.02) and in persistently overhydrated patients (OR: 9.57, 95% CI: 1.18-77.5, p = 0.03) even after adjustment to age, serum albumin and acute kidney injury (AKI) in stages 2-3. Time to death was shorter in overhydrated patients (HR: 2.82, 95% CI: 1.05-7.5, log-rank test p = 0.03). Abnormalities in FS associated with mortality were only identified by BIA in critically ill patients with COVID-19.

Adverse Events and Drug Resistance in Critically Ill Patients Treated with Colistimethate Sodium: A Review of the Literature.

The adverse events related to sodium colistimethate have had variability regarding the prevalence of nephrotoxicity, neurotoxicity, and less frequent respiratory depression. In recent years, its use has been relevant due to the increase of multidrug-resistant bacteria since it is considered the last-line drug, being its main adverse event and reason for discrepancies between authors' nephrotoxicity. The indiscriminate use of antibiotic therapy has generated multiple mechanisms of resistance, the most common being related to Colistin, the bactericidal escape effect. Based on the search criteria, no randomized clinical trials were identified showing safety and efficacy with the use of Colistin, inferring that the application of the appropriate dose is governed by expert opinion and retrospective and prospective observational studies, which confounding factors such as the severity of the patient and the predisposition to develop acute renal failure are constant. In this review, we focus on identifying the mechanism of nephrotoxicity and bacterial resistance, where much remains to be known.

Longitudinal Analysis of Urinary Cytokines and Biomarkers in COVID-19 Patients with Subclinical Acute Kidney Injury.

In hospitalized COVID-19 patients, disease progression leading to acute kidney injury (AKI) may be driven by immune dysregulation. We explored the role of urinary cytokines and their relationship with kidney stress biomarkers in COVID-19 patients before and after the development of AKI. Of 51 patients, 54.9% developed AKI. The principal component analysis indicated that in subclinical AKI, epidermal growth factor (EGF) and interferon (IFN)-α were associated with a lower risk of AKI, while interleukin-12 (IL-12) and macrophage inflammatory protein (MIP)-1ß were associated with a higher risk of AKI. After the manifestation of AKI, EGF and IFN-α remained associated with a lower risk of AKI, while IL-1 receptor (IL-1R), granulocyte-colony stimulating factor (G-CSF), interferon-gamma-inducible protein 10 (IP-10) and IL-5 were associated with a higher risk of AKI. EGF had an inverse correlation with kidney stress biomarkers. Subclinical AKI was characterized by a significant up-regulation of kidney stress biomarkers and proinflammatory cytokines. The lack of EGF regenerative effects and IFN-α antiviral activity seemed crucial for renal disease progression. AKI involved a proinflammatory urinary cytokine storm.

What Did We Learn about Coronavirus Disease-19-Associated Acute Kidney Injury During the Pandemic?

ABSTRACT Initial reports suggested that kidney involvement after coronavirus disease 19 (COVID-19) infection was uncommon, but this premise appears to be incorrect. Acute kidney injury can occur through various mechanisms and complicate the course of up to 25% of patients with COVID-19 hospitalized in our Institution, and of over 50% of those on invasive mechanical ventilation. Mechanisms of injury include direct kidney injury and predominantly tubular, although glomerular injury has been reported, and resulting from severe hypoxic respiratory failure, secondary infection, and exposure to nephrotoxic drugs. The mainstay of treatment remains the prevention of progressive kidney damage and, in some cases, the use of renal replacement therapy. Although the use of blood purification techniques has been proposed as a potential treatment, results to date have not been conclusive. In this manuscript, the mechanisms of kidney injury by COVID-19, risk factors, and the mainstays of treatment are reviewed.

What did we learn about coronavirus disease-19-associated acute kidney injury during the pandemic?

Initial reports suggested that kidney involvement after coronavirus disease 19 (COVID-19) infection was uncommon, but this premise appears to be incorrect. Acute kidney injury can occur through various mechanisms and complicate the course of up to 25% of patients with COVID-19 hospitalized in our Institution, and of over 50% of those on invasive mechanical ventilation. Mechanisms of injury include direct kidney injury and predominantly tubular, although glomerular injury has been reported, and resulting from severe hypoxic respiratory failure, secondary infection, and exposure to nephrotoxic drugs. The mainstay of treatment remains the prevention of progressive kidney damage and, in some cases, the use of renal replacement therapy. Although the use of blood purification techniques has been proposed as a potential treatment, results to date have not been conclusive. In this manuscript, the mechanisms of kidney injury by COVID-19, risk factors, and the mainstays of treatment are reviewed.

Role of Urinary Kidney Stress Biomarkers for Early Recognition of Subclinical Acute Kidney Injury in Critically Ill COVID-19 Patients.

A high proportion of critically ill patients with COVID-19 develop acute kidney injury (AKI) and die. The 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 the early detection of AKI in this population. 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. The demographic information, comorbidities, clinical, and laboratory data were recorded. The study outcomes were the development of AKI and mortality during hospitalization. Of the 51 individuals that were studied, 25 developed AKI during hospitalization (49%). Of those, 12 had persistent AKI (23.5%). The risk factors for AKI were male gender (HR = 7.57, 95% CI: 1.28-44.8; p = 0.026) and [TIMP-2] × [IGFBP7] ≥ 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). AKI was frequent in critically ill COVID-19 patients. The combination of [TIMP-2] × [IGFBP7] together with clinical information, were useful for the identification of subclinical AKI in critically ill COVID-19 patients. The role of additional biomarkers and their possible combinations for detection of AKI in ritically ill COVID-19 patients remains to be explored in large clinical trials.

Low phase angle is associated with 60-day mortality in critically ill patients with COVID-19.

BACKGROUND: Malnutrition status, body composition indicators, and bioelectrical impedance analysis (BIA) parameters have been associated with increased risk of death in several pathologies. The aim of this study was to describe the associations between phase angle (PhA) indicators obtained by BIA with length of hospital stay, days on mechanical ventilation, and 60-day mortality in critically ill patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). METHODS: This is a prospective cohort of mechanically ventilated patients with coronavirus disease 2019 (COVID-19). We assessed nutrition risk and body composition with BIA within 48 h from intensive care unit admission. Logistic and linear regression models were used to analyze the association between variables and clinical outcomes. Survival analysis by PhA value was performed using Kaplan-Meier curves. RESULTS: Sixty-seven patients were included. PhA (odds ratio [OR], 0.36; P = .002), standardized PhA (SPA) (OR, 0.45; P = .001), and extracellular water/total body water ratio (OR, 3.25; P = .002) were significant predictors of 60-day mortality. PhA <3.85° in females and <5.25° in males showed good and fair discrimination, respectively, for mortality prediction. Using cutoff values, low PhA was associated with a significantly increased risk of 60-day mortality (hazard ratio, 3.08; 95% CI, 1.12-8.41; P = .02). No association was detected for SPA. CONCLUSION: Low PhA values could be a predictor of 60-day mortality in critically ill patients with COVID-19. This biological marker could be incorporated as part of nutrition and mortality risk assessment in this population.

Acute kidney injury in patients with severe COVID-19 in Mexico.

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 invasive mechanical ventilation (IMV) and hospitalization, mechanical-ventilator settings and use of vasoactive drugs were recorded. RESULTS: Of 99 patients studied, 58 developed AKI (58.6%). The risk factors for AKI were older age (OR = 1.07, 95% CI = 1.01-1.13, p = 0.024); obesity (OR = 6.58, 95% CI = 1.8-24.05, p = 0.040); and the need for IMV (OR = 6.18, CI = 1.29-29.58, p = 0.023). The risk factors for mortality were obesity (OR = 5.57, 95% CI = 1.48-20.93, p = 0.011); requirement of vasoactive drugs on admission (OR = 5.35, 95% CI = 1.16-24.61, p = 0.031); and AKI (OR = 8.61, 95% CI = 2.24-33.1, p = 0.002). In-hospital mortality was significantly higher in patients with AKI stage 3 (79.3%) and AKI stage 2 (68.7%) compared with those with AKI stage 1 (25%; p = 0.004). Fifty-three patients underwent the furosemide stress test (FST) to predict progression to AKI stage 3. Of those, 12 progressed to AKI stage 3 (22%). The ROC curve for the FST had an AUC of 0.681 (p = 0.009); a sensitivity of 81.6% and a specificity of 54.5%. CONCLUSIONS: AKI was common in our cohort of patients with severe pneumonia caused by SARS-CoV-2 infection. The risk factors for AKI were older age, obesity and the need for of IMV on admission. The risk factors for mortality were obesity, requirement of vasoactive drugs on admission and AKI. Mortality was more frequent in patients with AKI stages 2-3. The FST had an acceptable predictive capacity to identify patients progressing to AKI stage 3.

Aggressive fluid accumulation is associated with acute kidney injury and mortality in a cohort of patients with severe pneumonia caused by influenza A H1N1 virus.

INTRODUCTION: Fluid accumulation is associated with adverse outcomes such as acute kidney injury (AKI) in critically ill patients. This study aimed to describe the factors associated with AKI in individuals with influenza A H1N1 severe pneumonia, and explore the relation of fluid accumulation with AKI and mortality. MATERIAL AND METHODS: We reviewed medical records of individuals with influenza A H1N1 severe pneumonia and no history of chronic kidney disease, attending a national referral center for respiratory diseases between November 2014 and May 2015. Demographic information, risk factors for AKI, physiologic and laboratory data, outcomes and information on fluid intake and output were recorded. Categorical variables were compared using the chi-square test. Quantitative variables were compared using the Mann-Whitney test. Factors associated with AKI and mortality were identified by binary logistic regression. Linear models of fluid accumulation rates for individuals and groups were estimated using segmented linear regression. RESULTS: Of 60 patients studied, 43 developed AKI (71.6%). Male gender was protective for AKI (p = 0.019). AKI was associated with nephrotoxic drugs (p = 0.016); PEEP>10 cm H2O on admission (p = 0.031); mortality (p = 0.037); and fluid accumulation ≥10% (fluid overload) at day 7 of hospitalization (p = 0.00026). Mortality was associated with older age (p = 0.009); nephrotoxic drugs (p = 0.034); and higher Pneumonia Severity Index score (112 vs. 76, p = 0.008) on admission. The Deceased-AKI group had a higher rate of fluid accumulation (expressed as ml/kg/body weight) than the Survivors-No AKI group during the study period of 7 days (Survivors-No AKI = 13.31 vs. Deceased-AKI = 22.76, p = 0.019). During the highest phase of fluid accumulation, the Survivors-No AKI group had a slower rate of fluid accumulation than the Survivors-AKI group (14.91 vs. 28.49, p = 0.001). CONCLUSIONS: A high rate of fluid accumulation was associated with AKI and mortality. We support the approach of resuscitation in acute illness, with an early transition to neutral and then negative fluid balances.

Hsp72 is a novel biomarker to predict acute kidney injury in critically ill patients.

BACKGROUND AND OBJECTIVES: Acute kidney injury (AKI) complicates the course of disease in critically ill patients. Efforts to change its clinical course have failed because of the fail in the early detection. This study was designed to assess whether heat shock protein (Hsp72) is an early and sensitive biomarker of acute kidney injury (AKI) compared with kidney injury molecule (Kim-1), neutrophil gelatinase-associated lipocalin (NGAL), and interleukin-18 (IL-18) biomarkers. METHODS: A total of 56 critically ill patients fulfilled the inclusion criteria. From these patients, 17 developed AKI and 20 were selected as controls. In AKI patients, Kim-1, IL-18, NGAL, and Hsp72 were measured from 3 days before and until 2 days after the AKI diagnosis and in no-AKI patients at 1, 5 and 10 days after admission. Biomarker sensitivity and specificity were determined. To validate the results obtained with ROC curves for Hsp72, a new set of critically ill patients was included, 10 with AKI and 12 with no-AKI patients. RESULTS: Urinary Hsp72 levels rose since 3 days before the AKI diagnosis in critically ill patients; this early increase was not seen with any other tested biomarkers. Kim-1, IL-18, NGAL, and Hsp72 significantly increased from 2 days before AKI and remained elevated during the AKI diagnosis. The best sensitivity/specificity was observed in Kim-1 and Hsp72: 83/95% and 100/90%, respectively, whereas 1 day before the AKI diagnosis, the values were 100/100% and 100/90%, respectively. The sensibility, specificity and accuracy in the validation test for Hsp72 were 100%, 83.3% and 90.9%, respectively. CONCLUSIONS: The biomarker Hsp72 is enough sensitive and specific to predict AKI in critically ill patients up to 3 days before the diagnosis.