Search

Introduction: Drug-induced acute kidney injury (DI-AKI) is a frequent adverse event. The identification of DI-AKI is challenged by competing etiologies, clinical heterogeneity among patients, and a lack of accurate diagnostic tools. Our research aims to describe the clinical characteristics and predictive variables of DI-AKI., Methods: We analyzed data from the Drug-Induced Renal Injury Consortium (DIRECT) study (NCT02159209), an international, multicenter, observational cohort study of enriched clinically adjudicated DI-AKI cases. Cases met the primary inclusion criteria if the patient was exposed to at least 1 nephrotoxic drug for a minimum of 24 hours prior to AKI onset. Cases were clinically adjudicated, and inter-rater reliability (IRR) was measured using Krippendorff's alpha. Variables associated with DI-AKI were identified using L1 regularized multivariable logistic regression. Model performance was assessed using the area under the receiver operating characteristic curve (ROC AUC)., Results: A total of 314 AKI cases met the eligibility criteria for this analysis, and 271 (86%) cases were adjudicated as DI-AKI. The majority of the AKI cases were recruited from the United States (68%). The most frequent causal nephrotoxic drugs were vancomycin (48.7%), nonsteroidal antiinflammatory drugs (18.2%), and piperacillin/tazobactam (17.8%). The IRR for DI-AKI adjudication was 0.309. The multivariable model identified age, vascular capacity, hyperglycemia, infections, pyuria, serum creatinine (SCr) trends, and contrast media as significant predictors of DI-AKI with good performance (ROC AUC 0.86)., Conclusion: The identification of DI-AKI is challenging even with comprehensive adjudication by experienced nephrologists. Our analysis identified key clinical characteristics and outcomes of DI-AKI compared to other AKI etiologies., (© 2023 International Society of Nephrology. Published by Elsevier Inc.)

A marine yeast, Yarrowia lipolytica, was evaluated for morphological, physiological and biochemical responses towards uranium (U) exposure at pH 7.5. The yeast revealed biphasic U binding - a rapid biosorption resulting in ∼35% U binding within 15-30 min followed by a slow biomineralization process, binding up to ∼45.5% U by 24 h on exposure to 50 μM of uranyl carbonate. Scanning electron microscopy coupled with Energy Dispersive X-ray spectroscopy analysis of 24 h U challenged cells revealed the deposition of uranyl precipitates due to biomineralization. The loss of intracellular structures together with surface and subcellular localization of uranyl precipitates in 24 h U exposed cells were visualized by transmission electron microscopy. Cells treated with 50 μM U exhibited membrane permeabilization which was higher at 200 μM U. Enhanced reactive oxygen species (ROS) accumulation and lipid peroxidation, transient RNA degradation and protein oxidation were observed in U exposed cells. High superoxide dismutase levels coupled with uranium binding and bioprecipitation possibly helped in counteracting U stress in 50 μM U treated cells. Resistance to U toxicity apparently developed under prolonged uranyl (50 μM) incubations. However, cells could not cope up with toxicity at 200 μM U due to impairment of resistance mechanisms., (Copyright © 2019 Elsevier B.V. All rights reserved.)