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.

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.

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.