Urinary micrornas are potential biomarkers of severity of urinary tract dysfunction in patients with posterior urethral valves

You have accessJournal of UrologyCME1 Apr 2023MP53-19 URINARY MICRORNAS ARE POTENTIAL BIOMARKERS OF SEVERITY OF URINARY TRACT DYSFUNCTION IN PATIENTS WITH POSTERIOR URETHRAL VALVES Elizabeth Mann, Melissa Mogle, Aditi Paranjpe, Marion Schulte, and Pramod Reddy Elizabeth MannElizabeth Mann More articles by this author , Melissa MogleMelissa Mogle More articles by this author , Aditi ParanjpeAditi Paranjpe More articles by this author , Marion SchulteMarion Schulte More articles by this author , and Pramod ReddyPramod Reddy More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003301.19AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Current management strategy for patients presenting with posterior urethral valves (PUV) includes monitoring of renal function to determine when urinary tract (UT) intervention such as intermittent catheterization or urinary diversion is indicated. The challenge with this approach is that ongoing renal injury may no longer be reversible and exposes the child to progression of chronic kidney disease (CKD). We hypothesize that microRNAs (miRNA) derived from urinary small extracellular vesicles (sEV) reflect the physiological status of the UT and may serve as real-time indicators of lower urinary tract injury. These biomarkers could permit the development of a proactive strategy of serial monitoring of the lower UT in patients with PUV and permit timely intervention prior to the progression of renal injury. METHODS: We have undertaken an IRB approved prospective study. Informed consent was obtained at time of enrollment. Urine samples are collected for each patient at least once a year and urinalysis performed. We excluded samples with active infections. Patients (1-18 yrs) with PUV were stratified into clinical categories based on the severity of the involvement of their UT. Patients with isolated genital pathology and a normal UT served as negative controls. sEVs were isolated from the urine by ultracentrifugation and total RNA extracted. Next-generation small RNA sequencing and differential expression analysis was performed. RT-qPCR was used to verify the expression of candidate miRNAs. RESULTS: A total of 76 PUV Patients and 35 controls have been enrolled in the study, with 244 urine samples collected. Principle component analysis of the most variable miRNAs demonstrated a clear clustering of the patients in the moderate/severe category compared to the patients with mild disease and non-PUV controls. We have identified 61 miRNAs that were upregulated and 45 miRNAs that were downregulated in the moderate/severe patients (≥1.5-fold, p≤0.05). We selected 4 miRNAs to analyze further by RT-qPCR and confirmed the decreased expression of miRNA-30a-5p in moderate/severe cases (>5-fold, p≤0.01). CONCLUSIONS: This study demonstrates that urinary miRNAs can serve as biomarkers of the severity of UT dysfunction in patients with PUV. Ongoing studies seek to further validate these findings. The development of a noninvasive urinary assay for a set of predictive miRNA biomarkers will enhance our ability to care for patients with PUV and enable real-time assessment of the health of their lower urinary tract. Source of Funding: None © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e719 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Elizabeth Mann More articles by this author Melissa Mogle More articles by this author Aditi Paranjpe More articles by this author Marion Schulte More articles by this author Pramod Reddy More articles by this author Expand All Advertisement PDF downloadLoading ...