Abstract
Background:Acute kidney injury (AKI) is a common complication of hospitalization with high morbidity and mortality for which no effective treatments exist and for which current diagnostic tools have limitations for earlier identification. MicroRNAs (miRNAs) are small non-coding RNAs that have been implicated in the pathogenesis of AKI, and some miRNAs have shown promise as therapeutic tools in animal models of AKI. However, less is known about the role of miRNAs in human AKI.Objective:To evaluate the role of miRNAs in human subjects with AKI.Design:Systematic review and meta-analysisMeasurements:Quantification of miRNA levels from human blood, urine, or kidney biopsy samples, and measures of renal function as defined in the study protocol.Methods:A comprehensive search strategy for Ovid MEDLINE All, Embase, Web of Science, and CENTRAL will be developed to identify investigational studies that evaluated the relationship between miRNA levels and human AKI. Primary outcomes will include measurements of kidney function and miRNA levels. Study screening, review and data extraction will be performed independently by 2 reviewers. Study quality and certainty of evidence will be assessed with validated tools. A narrative synthesis will be included and the possibility for meta-analysis will be assessed according to characteristics of clinical and statistical heterogeneity between studies.Limitations:These include (1) lack of randomized trials of miRNAs for the prevention or treatment of human AKI, (2) quality of included studies, and (3) sources of clinical and statistical heterogeneity that may affect strength and reproducibility of results.Conclusion:Previous studies of miRNAs in different animal models of AKI have generated strong interest on their use for the prevention and treatment of human AKI. This systematic review will characterize the most promising miRNAs for human research and will identify methodological constraints from miRNA research in human AKI to help inform the design of future studies.Systematic review registration:PROSPERO CRD42020201253
Highlights
Acute kidney injury (AKI) is a common complication of hospitalization with high morbidity and mortality for which no effective treatments exist and for which current diagnostic tools have limitations for earlier identification
Acute kidney injury affects up to 20% of hospitalized patients in those admitted to intensive care units (ICU).[1]
In a meta-analysis of 82 studies with 2 million hospitalized adults followed for minimum 1 year, AKI was associated with a nearly 2-fold increased risk of death, a 3-fold increased risk of new or progressive chronic kidney disease (CKD), and a 4-fold increased risk of kidney failure compared to patients without AKI.[2]
Summary
Acute kidney injury (AKI) is a common complication of hospitalization with high morbidity and mortality for which no effective treatments exist and for which current diagnostic tools have limitations for earlier identification. In a meta-analysis of 82 studies with 2 million hospitalized adults followed for minimum 1 year, AKI was associated with a nearly 2-fold increased risk of death, a 3-fold increased risk of new or progressive chronic kidney disease (CKD), and a 4-fold increased risk of kidney failure compared to patients without AKI.[2] The incremental cost of AKI in Canada is estimated to exceed CAN$200 million per year, and greater severity AKI is associated with incremental increases in both hospital length of stay and costs.[3] Despite the health and economic burden of AKI, no effective interventions currently exist for treatment,[4] preventative measures are limited,[5] and current diagnostic tools including serum creatinine and urine output have major limitations for earlier identification.[6]
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