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Victor Hugo Ahumada Topete,1,* Kevin Jesus de Dios Sanchez,1,* Gustavo Alejandro Casas Aparicio,2 Graciela Hernandez Silva,2 Cesar Emmanuel Lopez Vejar,1 Luz Maria Torres Espíndola,3 Arnoldo Aquino-Galvez,4 Odalis Rodriguez Ganen,5 Manuel de Jesus Castillejos Lopez1 1Hospital Epidemiology and Infectology Unit, National Institute of Respiratory Diseases Ismael Cosío Villegas, Mexico City, Mexico; 2Department of Infectious Disease Research, National Institute of Respiratory Diseases Ismael Cosío Villegas, Mexico City, Mexico; 3Laboratory of Pharmacology, National Institute of Pediatrics, Mexico City, Mexico; 4Molecular Biology Laboratory, National Institute of Respiratory Diseases Ismael Cosío Villegas, Mexico City, Mexico; 5Department of Hospital Pharmacy, National Institute of Respiratory Diseases Ismael Cosío Villegas, Mexico City, Mexico*These authors contributed equally to this workCorrespondence: Manuel de Jesus Castillejos Lopez; Arnoldo Aquino Galvez, Email mcastillejos@gmail.com; araquiga@yahoo.comAbstract: 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.Keywords: colistin, colistimethate, nephrotoxicity, neurotoxicity, resistance mechanism, multidrug-resistant gram-negative bacteria, risk factors, high doses, toxicity

Background: Patients with COVID-19 may experience a persistent increase in the blood urea nitrogen over creatinine ratio (PI-BUN/Cr). Its elevation could reflect multiple underlying pathophysiological processes beyond prerenal injury but also warrants nuanced interpretation due to its complex interplay with various factors, underscoring the importance of investigating its effects on mortality and acute kidney injury in this population., Methods: We analized a retrospective and longitudinal cohort of patients admitted to a single center in Mexico City for patients with severe COVID-19. Between March 5, 2020 and August 25, 2021, we included patients with confirmed positive diagnosis for SARS-CoV-2, age > 18 years, disease severity was defined by clinical data of respiratory distress syndrome and a ratio of partial oxygen pressure to inspired oxygen fraction < 300 mmHg on admission. We excluded patients with End Stage Kidney Disease. Data was obtained from electronic medical records. PI-BUN/Cr was defined as an increase in the BUN/Cr ratio > 30 in more than 60% of measurements in the hospital. The outcomes included: risk factors to mortality and AKI in-hospital., Results: The cohort included 3,007 patients with a median age of 54.6 ± 14.5 years. 35% of patients died; 44.6% developed PI-BUN/Cr ratio and 71.4% AKI. Mortality was associated with older age > 60 years [Hazard ratio (HR)] = 1.45, 95% CI: 1.28-1.65; p < 0.001); male (HR 1.25, 95% CI 1.09-1.44; p = 0.002) and AKI (HR 3.29, 95% CI 2.42-4.46; p < 0.001); PI-BUN/CR & Non-AKI (HR = 2.82, 95% CI: 1.61-4.93; p < 0.001); Non PI-BUN/CR & AKI (HR = 5.47, 95% CI: 3.54-8.44; p < 0.001); and PI-BUN/CR & AKI (HR = 4.26, 95% CI: 2.75-6.62, p < 0.001). Only hiperuricemia was a risk factor for AKI (HR = 1.71, 95% CI: 1.30-2.25, p < 0.001)., Conclusions: While PI-BUN/Cr alone may not directly associate with mortality, its capacity to sub-phenotype patients according to their AKI status holds significant promise in offering valuable insights into patient prognosis and outcomes. Understanding the nuanced relationship between PI-BUN/Cr and AKI enhances our comprehension of renal function dynamics. It equips healthcare providers with a refined tool for risk stratification and personalized patient management strategies., (© 2024. The Author(s).)

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.

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.

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)-1β 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.

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.

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.