Increased urinary exosomal microRNAs in children with idiopathic nephrotic syndrome
Tingting Chen1, Cheng Wang1, Hanqing Yu2
1Department of Clinical Laboratory, Jinling Hospital, Nanjing School of Clinical Medicine, Southern Medical University, State Key Laboratory of Analytical Chemistry for Life Science, Nanjing, China; State Key Laboratory of Pharmaceutical Biotechnology, Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, Advance Research Institute of Life Sciences, Nanjing University, School of Life Sciences, Nanjing, China.
Background:
Urinary exosomal miRNAs are gaining increasing attention for their potential as ideal non-invasive biomarkers for kidney diseases; however, little is known about their diagnostic ability for paediatric nephrotic syndrome (NS). This study explored the clinical value of urinary exosomal miRNAs for paediatric idiopathic NS.
Methods:
Urine samples were collected from 129 NS children and 126 age-/sex-matched healthy controls. The miRNA profile of urinary exosomes was analysed by high-throughput Illumina sequencing via synthesis (SBS) technology followed by verification with a quantitative reverse-transcription polymerase chain reaction (RT-qPCR) assay arranged in two independent cohorts. Additionally, paired urine samples from 65 of these patients were collected before and after treatment.
Findings:
The Illumina SBS identified 30 markedly increased urinary exosomal miRNAs in NS children compared with controls (≥ 5-fold, P < .05). Fifteen miRNAs were selected for further investigation, of which 5 (miR-194-5p, miR-146b-5p, miR-378a-3p, miR-23b-3p and miR-30a-5p) were verified by RT-qPCR to be significantly and steadily increased in NS (> 3-fold, P < .01) and markedly reduced during the clinical remission period (P < .001). Moreover, the concentrations of miR-194-5p and miR-23b-3p were significantly positively correlated with the urine protein content and were markedly higher in the high urine protein group than in the low urine protein group (P < .001 and P < .01, respectively).
Interpretations:
We identified 5 altered urinary exosomal miRNAs in NS children with disease progression and treatment. These urinary exosomal miRNAs could be promising and non-invasive potential biomarker candidates for diagnosing, monitoring and stratifying paediatric NS. FUND: National Natural Science Foundation of China; Fund of State Key Laboratory of Analytical Chemistry for Life Science; National Basic Research Programme of China; Foundation of Jiangsu Provincial Medical Youth Talent.
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