URINARY EXOSOMAL MIRNAS AS BIOMARKERS IN CHRONIC KIDNEY DISEASE PROGRESSION

Abstract

Chronic Kidney Disease (CKD) remains a global health burden, necessitating novel biomarkers for early detection and progression monitoring. This study investigated the utility of urinary exosomal microRNAs (miRNAs) as non-invasive biomarkers in CKD by profiling their expression across varying disease stages. A cohort comprising 60 CKD patients (stages 1–5) and 30 healthy controls was analyzed. Urinary exosomes were isolated and characterized using electron microscopy and nanoparticle tracking, followed by RNA extraction and qRT-PCR to quantify selected miRNAs, including miR-21, miR-29a, miR-192, miR-200c, and miR-223. The results demonstrated significant upregulation of miR-192 (4.8-fold), miR-21 (3.5-fold), and miR-200c (3.0-fold) in stage 5 CKD patients compared to controls (p < 0.01). These miRNAs were strongly correlated with decreased eGFR (r = –0.72 for miR-192) and increased serum creatinine, indicating their potential in reflecting renal dysfunction. Further, the gut-derived uremic toxins that were extremely high in stage 5 patients included indoxyl sulfate and p-cresyl sulfate which showed positive correlation (r= 0.68 and 0.60) with miR-192 expression and systemic inflammation (CRP levels). The findings from these studies emphasize the crosstalk between the gut microbiome, toxic uremic build-up and the miRNA derangement at the gut-kidney axis. The research also revealed that urinary exosomal miRNAs provide a robust, reliable, accessible and sensitive platform for post-CKD progression and metabolic problems screening. Due to their association with the existing renal function markers and inflammatory mediators with good correlations, these miRNAs can contribute to risk stratification and timely clinical interventions. In conclusion, urinary exosomal miRNAs, and particularly miR-192, become promising non-invasive biomarkers with diagnostic and prognostic significance in CKD, which needs further validation in bigger and more diverse cohorts.