Accuracy of Urine Kidney Injury Molecule-1 in Predicting Acute Kidney Injury in Children; a Systematic Review and Meta-Analysis
ARCHIVES OF ACADEMIC EMERGENCY MEDICINE
Authors: Fazel, Mojtaba; Sarveazad, Mash; Ali, Kosar Mohamed; Yousefifard, Mahmoud; Hosseini, Mostafa
Abstract
Introduction: There is considerable controversy on the accuracy of Kidney InjuryMolecule-1 (KIM-1) in prediction of acute kidney injury (AKI) in children. Therefore, the present study intends to provide a systematic review and meta-analysis of the value of this biomarker in predicting AKI in children. Methods: An extensive search was performed on the Medline, Embase, Scopus and Web of Science databases by the end of 2019. Cohort and case-control studies on children were included. Urinary KIM-1 levels were compared between AKI and non-AKI groups. Findings were reported as an overall standardized mean difference (SMD) with a 95% confidence interval (CI). Also, the overall area under the receiver operating characteristic (ROC) curve (AUC) of KIM-1 in predicting AKI in children was calculated. Results: Data from 13 articles were included. Urinary KIM-1 levels in children with stage 1 AKI were higher than the non-AKI group only when assessed within the first 12 hours after admission (SMD = 0.95; 95% CI: 0.07 to 1.84; p = 0.034). However, urinary KIM-1 levels in children with stage 2-3 AKI were significantly higher than non-AKI children (p < 0.01) at all times. The AUC of urinary KIM-1 in predicting AKI in children was 0.69 (95% CI: 0.62 to 0.77). Conclusion: Based on the available evidence, KIM-1 seems to have moderate value in predicting AKI in children. Since previous meta-analyses have provided other urinary and serum biomarkers that have better discriminatory accuracy than KIM-1, so it had better not to use KIM-1 in predicting AKI in children.
In vitro study of putative genomic biomarkers of nephrotoxicity through differential gene expression using gentamicin
TOXICOLOGY MECHANISMS AND METHODS
Authors: Teixeira Silva, Sarah Cristina; de Almeida, Leonardo Augusto; Soares, Stellamaris; Grossi, Marina Felipe; Santana Valente, Anete Maria; Tagliati, Carlos Alberto
Abstract
Drug-induced nephrotoxicity is one of the most frequently observed effects in long-term pharmacotherapy. The effects of nephrotoxicity are commonly discovered later due to a lack of sensitivity in in vivo methods. Therefore, researchers have tried to develop in vitro alternative methods for early identification of toxicity. In this study, LLC-PK1 cells were exposed to gentamicin through MTT and trypan blue assay. Concentrations of 4 (low), 8 (medium) and 12 (high) mM, were used to evaluate differential gene expression. A panel of genes was selected based on gene expression changes. The search for sequences of mRNA encoding proteins previously associated with kidney damage was conducted in the databases of the National Center for Biotechnology Information (USA). RNA was extracted from the cells, and RT-qPCR was performed to evaluate differential expression profiles of the selected genes. Among the 11 analyzed genes, four proved to be differentially up-regulated in cells exposed to gentamicin: HAVcr1, caspase 3, ICAM-1 and EXOC6. According to this study's results, we suggest that these genes play an important role in the mechanism of in vitro nephrotoxicity caused by gentamicin and can be used as early in vitro biomarkers to identify nephrotoxicity when developing safer drugs.