1. Therapeutic effects of micro-RNAs in preclinical studies of acute kidney injury: a systematic review and meta-analysis
- Author
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Adrian Bailey, Kevin D. Burns, Jose L. Viñas, Rosendo A. Rodriguez, Sarah Zankar, David S. Allan, and Mayra Trentin-Sonoda
- Subjects
0301 basic medicine ,Male ,Science ,030232 urology & nephrology ,Drug Evaluation, Preclinical ,Renal function ,Apoptosis ,Pathogenesis ,Bioinformatics ,Kidney ,Article ,03 medical and health sciences ,chemistry.chemical_compound ,Mice ,0302 clinical medicine ,medicine ,PTEN ,Animals ,Adverse effect ,Creatinine ,Multidisciplinary ,Kidney diseases ,biology ,business.industry ,Acute kidney injury ,Antagomirs ,Acute Kidney Injury ,medicine.disease ,3. Good health ,Rats ,Experimental models of disease ,MicroRNAs ,030104 developmental biology ,medicine.anatomical_structure ,chemistry ,Nephrology ,Preclinical research ,Meta-analysis ,biology.protein ,Medicine ,Female ,business ,Kidney disease - Abstract
AKI has a high mortality rate, may lead to chronic kidney disease, and effective therapies are lacking. Micro-RNAs (miRNAs) regulate biologic processes by potently inhibiting protein expression, and pre-clinical studies have explored their roles in AKI. We conducted a systematic review and meta-analysis of miRNAs as therapeutics in pre-clinical AKI. Study screening, data extraction, and quality assessments were performed by 2 independent reviewers. Seventy studies involving 42 miRNA species were included in the analysis. All studies demonstrated significant effects of the miRNA intervention on kidney function and/or histology, with most implicating apoptosis and phosphatase and tensin homolog (PTEN) signaling. Fourteen studies (20.0%) examined the effect of miRNA-21 in AKI, and meta-analysis demonstrated significant increases in serum creatinine and kidney injury scores with miR-21 antagonism and pre-conditioning. No studies reported on adverse effects of miRNA therapy. Limitations also included lack of model diversity (100% rodents, 61.4% ischemia–reperfusion injury), and predominance of male sex (78.6%). Most studies had an unclear risk of bias, and the majority of miRNA-21 studies were conducted by a single team of investigators. In summary, several miRNAs target kidney function and apoptosis in pre-clinical AKI models, with data suggesting that miRNA-21 may mediate protection and kidney repair.Systematic review registration ID: CRD42019128854.
- Published
- 2021