The potential utility of microRNAs (miRNAs) as diagnostic or prognostic biomarkers, as well as therapeutic targets, for chronic kidney disease (CKD) has been advocated. However, studies evaluating the expression profile of the same miRNA signatures in CKD report contradictory findings. This review aimed to characterize miRNAs associated with CKD and/or measures of kidney function and kidney damage in the general population, and also in high-risk subgroups, including people with hypertension (HTN), diabetes mellitus (DM) and human immunodeficiency virus (HIV) infection. Medline via PubMed, Scopus, Web of Science, and EBSCOhost databases were searched to identify relevant studies published in English or French languages on or before 30 September 2022. A total of 75 studies fulfilled the eligibility criteria: CKD (n = 18), diabetic kidney disease (DKD) (n = 51) and HTN-associated CKD (n = 6), with no study reporting on miRNA profiles in people with HIV-associated nephropathy. In individuals with CKD, miR-126 and miR-223 were consistently downregulated, whilst in DKD, miR-21 and miR-29b were consistently upregulated and miR-30e and let-7a were consistently downregulated in at least three studies. These findings suggest that these miRNAs may be involved in the pathogenesis of CKD and therefore invites further research to explore their clinical utility for CKD prevention and control.
The asymptomatic nature of and lack of effective early-stage diagnostic tools in CKD, predisposes individuals to the risk of end-stage CKD and related complications. Whole blood microRNAs (miRNAs) have the potential for CKD risk screening. We evaluated the expression profile of six novel whole blood miRNAs as well as their ability to predict prevalent CKD in individuals with hypertension and/or diabetes. We included 911 individuals with hypertension and/or diabetes, of which 18.8% had prevalent CKD. The miRNA expression was analyzed using quantitative reverse transcription PCR (RT-PCR). Five of the six miRNAs, namely hsa-miR-novel-chr1_36178, hsa-miR-novel-chr2_55842, hsa-miR-novel-chr7_76196, hsa-miR-novel-chr5_67265, and hsa-miR-novel-chr13_13519, were significantly increased in people with CKD (all p < 0.028). Only the increased expression of hsa-miR-novel-chr2_55842 and hsa-miR-novel-chr7_76196 were independently associated with reduced estimated glomerular filtration rate (eGFR) (both p ≤ 0.038), while all the analyzed miRNAs were positively associated with prevalent CKD (all p ≤ 0.038). All the blood miRNAs were acceptable predictors of CKD (C-statistic > 0.7 for all), with similar predictive capacity (p = 0.202). However, hsa-miR-novel-chr13_13519 added to CKD prediction beyond conventional factors (p = 0.040). Novel whole blood miRNAs showed an acceptable discriminative power to predict prevalent CKD; thereby suggesting the potential use of these miRNAs, particularly hsa-miR-novel-chr13_13519, in clinical practice as a screening tool for CKD in high-risk individuals.
IntroductionChronic kidney disease (CKD) is a significant health and economic burden, owing to its ever-increasing global prevalence. Due to the limitations in the current diagnostic methods, CKD is frequently diagnosed at advanced stages, where there is an increased risk of cardiovascular complications and end-stage kidney disease. As such, there has been considerable interest in microRNAs (miRNAs) as potential markers for CKD detection. This review seeks to identify all miRNAs associated with CKD and/or markers of kidney function or kidney damage in the general population and high-risk subgroups, and explore their expression profiles in these populations.Methods and analysisA systematic search of published literature will be conducted for observational studies that report on miRNAs associated with CKD or kidney function or kidney damage markers (serum creatinine and cystatin C, estimated glomerular filtration rate and urinary albumin excretion) in adult humans. The electronic database search will be restricted to English and French publications up to 31 October 2021. Two investigators will independently screen and identify studies for inclusion, as well as extract data from eligible studies. Risk-of-bias and methodological quality will be assessed by the Newcastle-Ottawa Quality Assessment Scale for observational studies and Grading of Recommendations Assessment, Development and Evaluation tools. Appropriate meta-analytic techniques will be used to pool estimates from studies with similar miRNAs, overall and by major characteristics, including by country or region, sample size, gender and risk-of-bias score. Heterogeneity of the estimates across studies will be quantified and publication bias investigated. This protocol is reported according to Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols 2015 guidelines.Ethics and disseminationThis study design does not require formal ethical clearance and findings will be published in a peer-reviewed journal.ConclusionThis review will provide the expression pattern of miRNAs associated with CKD. This will allow for further research into the identified miRNAs, which could later be used as biomarkers for prediction and early detection of CKD, monitoring of disease progression to advanced stages and as potential therapeutic targets.PROSPERO registration numberCRD42021270028.
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