MicroRNAs as Potential Biomarkers for the Diagnosis of Chronic Kidney Disease: A Systematic Review and Meta-Analysis

Abstract

For Chronic Kidney Disease (CKD), the study of microRNA as a biomarker has become an exciting area, so we carried out a meta-analysis to investigate the potential diagnostic values of miRNAs in CKD. We searched Pubmed, Cochrane Library, Embase, and Web of science databases to identify relevant publications published from the establishment of the database to April 30, 2021. We included a total of 26 articles containing 56 studies. There were 4,098 patients with CKD and 2,450 patients without CKD. We found that the overall sensitivity and specificity of miRNAs in CKD diagnosis were 0.86 (95% CI: 0.83–0.89) and 0.79 (95% CI: 0.75–0.83), respectively. In addition, we plotted the summary receiver operator characteristic (SROC) curve to assess diagnostic accuracy, with the area under the curve (AUC) of 0.90 (95% CI: 0.87–0.92). Subgroup analysis showed that sensitivity, specificity, and AUC of miRNAs in plasma and serum were 0.84, 0.78, 0.88; and 0.79, 0.76, 0.83, respectively, while miRNAs in urine were 0.89 for sensitivity, 0.82 for specificity, and 0.92 for AUC. Moreover, we found that the panel of microRNAs (miRNAs) could improve the pooled sensitivity (0.88, 0.81, and 0.91 for sensitivity, specificity, and AUC, respectively). We believe that miRNAs have great potential to become an effective diagnostic biomarker for CKD. Panels of miRNA have higher accuracy than single miRNAs. Additionally, miRNAs in both blood and urine have significant accuracy in the diagnosis of CKD; nevertheless, urine is superior.

MicroRNAs Associated with Chronic Kidney Disease in the General Population and High-Risk Subgroups—A Systematic Review

“…These discrepancies may be partly explained by the technical and methodological inter-study variabilities, such as the use of different biological samples, sample handling and processing procedures, miRNA extraction protocols, detection and quantification techniques, and normalizing controls [ 118 ]. Although the majority of included studies quantified miRNA expression in blood, recent evidence points to the superiority of urine miRNAs to serum/plasma miRNAs for CKD diagnosis with the non-invasive nature in which urine samples are collected, adding to its preference [ 119 ]. Another challenge is the lack of a standardized normalization control for miRNA expression studies.…”

Urinary microRNA profiling in pregnant women identifies placental microRNAs that are candidate biomarkers for monitoring placental health

“…Only limited medical fields have investigated urinary microRNA profiles. Examples are metabolic diseases, chronic kidney disease, and cancers such as clear cell renal cell carcinoma, and prostate cancer [8,13–16]. The main innovation of this study was to explore urinary microRNAs as a novel resource to be potentially utilized for monitoring the pregnancy course.…”

“…Only limited medical fields have investigated urinary microRNA profiles. Examples are metabolic diseases, chronic kidney disease, and cancers such as clear cell renal cell carcinoma, and prostate cancer [8,[13][14][15][16].…”

MicroRNA‐126 in dogs with immune complex‐mediated glomerulonephritis

“…4 Biofluid miRNAs could serve as promising noninvasive biomarkers of CKD onset, diagnosis, progression, therapeutic monitoring, and severity of kidney damage. [5][6][7] Circulating and urinary miRNAs are identified in humans with glomerular diseases. 6,[8][9][10][11][12][13][14] The most studied diagnostic categories include glomerulonephritis, diabetic nephropathy (DN), IgA nephropathy (IgA), acute kidney injury (AKI), and hypertensive nephropathy (HN), with a focus on miRNAs that affect the pathogenesis of tubulointerstitial fibrosis.…”

“…These miRNAs exist in cells and cell‐free biofluids, including serum, plasma, and urine 4 . Biofluid miRNAs could serve as promising noninvasive biomarkers of CKD onset, diagnosis, progression, therapeutic monitoring, and severity of kidney damage 5‐7 …”