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MicroRNAs as Biomarkers and Therapeutic Targets for Acute Kidney Injury.

ABSTRACT: Acute kidney injury (AKI) is a clinical syndrome where a rapid decrease in kidney function and/or urine output is observed, which may result in the imbalance of water, electrolytes and acid base. It is associated with poor prognosis and prolonged hospitalization. Therefore, an early diagnosis and treatment to avoid the severe AKI stage are important. While several biomarkers, such as urinary L-FABP and NGAL, can be clinically useful, there is still no gold standard for the early detection of AKI and there are limited therapeutic options against AKI. miRNAs are non-coding and single-stranded RNAs that silence their target genes in the post-transcriptional process and are involved in a wide range of biological processes. Recent accumulated evidence has revealed that miRNAs may be potential biomarkers and therapeutic targets for AKI. In this review article, we summarize the current knowledge about miRNAs as promising biomarkers and potential therapeutic targets for AKI, as well as the challenges in their clinical use.

SUBMITTER: Tsuji K

PROVIDER: S-EPMC10529274 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature

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MicroRNAs as Biomarkers and Therapeutic Targets for Acute Kidney Injury.

Tsuji Kenji K Nakanoh Hiroyuki H Fukushima Kazuhiko K Kitamura Shinji S Wada Jun J

Diagnostics (Basel, Switzerland) 20230909 18

Acute kidney injury (AKI) is a clinical syndrome where a rapid decrease in kidney function and/or urine output is observed, which may result in the imbalance of water, electrolytes and acid base. It is associated with poor prognosis and prolonged hospitalization. Therefore, an early diagnosis and treatment to avoid the severe AKI stage are important. While several biomarkers, such as urinary L-FABP and NGAL, can be clinically useful, there is still no gold standard for the early detection of AKI ...[more]

PMID: 37761260

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Project description:BackgroundSepsis and septic shock are life-threatening diseases with high mortality rate in intensive care unit (ICU). Acute kidney injury (AKI) is a common complication of sepsis, and its occurrence is a poor prognostic sign to septic patients. We analyzed co-differentially expressed genes (co-DEGs) to explore relationships between septic shock and AKI and reveal potential biomarkers and therapeutic targets of septic-shock-associated AKI (SSAKI).MethodsTwo gene expression datasets (GSE30718 and GSE57065) were downloaded from the Gene Expression Omnibus (GEO). The GSE57065 dataset included 28 septic shock patients and 25 healthy volunteers and blood samples were collected within 0.5, 24 and 48 h after shock. Specimens of GSE30718 were collected from 26 patients with AKI and 11 control patents. AKI-DEGs and septic-shock-DEGs were identified using the two datasets. Subsequently, Gene Ontology (GO) functional analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, and protein-protein interaction (PPI) network analysis were performed to elucidate molecular mechanisms of DEGs. We also evaluated co-DEGs and corresponding predicted miRNAs involved in septic shock and AKI.ResultsWe identified 62 DEGs in AKI specimens and 888, 870, and 717 DEGs in septic shock blood samples within 0.5, 24 and 48 h, respectively. The hub genes of EGF and OLFM4 may be involved in AKI and QPCT, CKAP4, PRKCQ, PLAC8, PRC1, BCL9L, ATP11B, KLHL2, LDLRAP1, NDUFAF1, IFIT2, CSF1R, HGF, NRN1, GZMB, and STAT4 may be associated with septic shock. Besides, co-DEGs of VMP1, SLPI, PTX3, TIMP1, OLFM4, LCN2, and S100A9 coupled with corresponding predicted miRNAs, especially miR-29b-3p, miR-152-3p, and miR-223-3p may be regarded as promising targets for the diagnosis and treatment of SSAKI in the future.ConclusionsSeptic shock and AKI are related and VMP1, SLPI, PTX3, TIMP1, OLFM4, LCN2, and S100A9 genes are significantly associated with novel biomarkers involved in the occurrence and development of SSAKI.

Project description:BackgroundAcute kidney injury (AKI) causes significant morbidity and mortality in humans, and there are currently no effective treatments to enhance renal recovery. MicroRNAs (miRNAs) are short chain nucleotides that regulate protein expression and have been implicated in the pathogenesis of AKI. Recently, preclinical studies in vivo have uncovered a therapeutic role for administration of specific miRNAs in AKI. However, the overall benefits of this strategy in preclinical studies have not been systematically reviewed, and the potential for translation to human studies is unclear.AimThe primary aim is to conduct a systematic review of the therapeutic properties of miRNAs in preclinical studies of AKI. The secondary aim is to determine potential adverse effects of miRNA administration in these studies.MethodsA comprehensive search strategy will identify relevant studies in AKI in vivo models, using the MEDLINE, EMBASE, OVID, PUBMED, and Web of Science databases. The search strategy will include terms for mammalian (non-human) AKI models, including injury related to ischemia/reperfusion, nephrotoxicity, sepsis, contrast agents, cardio-pulmonary bypass, and hemorrhagic shock. Interventions will be defined as direct administration of exogenous miRNAs or antagonists of miRNAs, as well as maneuvers that alter expression of miRNAs that are mechanistically linked to AKI outcomes. The primary outcomes will be indices of kidney function and structure, and there will be no restriction on comparator interventions. Two independent investigators will initially screen abstracts, and selected articles that meet eligibility criteria will be reviewed for data abstraction and analysis. The SYRCLE RoB tool for animal studies will determine risk of bias, and meta-analysis will be performed as appropriate. The GRADE methodology will assess the quality of evidence.DiscussionThe administration of selective miRNA mimics or antagonists exerts beneficial effects in mammalian models of AKI, although multiple obstacles must be addressed prior to translation to human clinical trials. The proposed systematic review will document key miRNA candidates, and determine effect size estimates and sources of outcome bias. The review will also identify gaps in knowledge and guide future directions in AKI research.Systematic review registrationPROSPERO CRD42019128854.

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MicroRNAs as Biomarkers and Therapeutic Targets for Acute Kidney Injury.

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MicroRNAs as Biomarkers and Therapeutic Targets for Acute Kidney Injury.

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