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Aims: Immunoglobulin A nephropathy (IgAN) is the most common primary glomerular disease to cause end‐stage kidney disease. This study investigated the difference in urinary exosomal circular RNA (circRNA) expression profiles between patients with IgAN and healthy controls (HCs), for better understanding of gene regulation in exosomes of IgAN patients. Methods: A pairwise comparison of urinary circRNA expression profiles between IgAN patients and HCs was performed using methods, including high‐throughput sequencing and quantitative polymerase chain reaction. Moreover, the potential functions of differentially expressed circRNAs (DECs) in IgAN were investigated by gene ontology (GO) enrichment analysis; Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis; and the circRNA‐miRNA‐mRNA network. Results: We identified 450 upregulated and 26 downregulated circRNAs in the IgAN patients. GO analysis showed that these enriched circRNAs might regulate primary miRNA processing, the ability of angiotensin receptor binding, and stress fibre function. KEGG analysis suggested these DECs may be closely associated with the phosphoinositide‐3‐kinase‐protein kinase B/Akt (PI3K‐Akt) signalling pathways. Network analysis revealed the relationship between circRNAs and their target genes. Conclusion: The identified DECs may be useful for both researches on molecular aetiology of IgAN and development of potentially novel non‐invasive biomarkers of IgAN. SUMMARY AT A GLANCE: An RNA‐sequence analysis of RNAs in urinary exosomes identified a number of differentially expressed circular RNAs in immunoglobulin A nephropathy (IgAN) patients as compared to healthy controls. These circRNAs are associated with the regulation of pathways relevant to IgAN and may provide useful non‐invasive biomarkers for this condition. [ABSTRACT FROM AUTHOR]

The present study aimed to detect the levels of microRNA (miR)-33a-5p in the renal tissue, serum and urine of patients with primary IgA nephropathy (IgAN), thereby preliminarily exploring the association between the levels of miR-33a-5p and the condition of primary IgAN to provide evidence for the expression of miR-33a-5p in the serum and urine of IgAN patients as a clinical marker. Reverse-transcription quantitative PCR was performed to evaluate the level of miR-33a-5p in IgAN patients according to severity and pathological classification. The results suggested that the levels of miR-33a-5p in the serum, urine and kidney tissues of patients with IgAN were lower than those of the control tissues obtained from cancer patients (0.28±0.25 vs. 1.00±0.45, P<0.05; 0.34±0.28 vs. 1.00±0.53, P<0.05; 0.47±0.27 vs. 1.00±0.38, P<0.05, respectively). Receiver operating characteristic curve analysis suggested that the serum and urine levels of miR-33a-5p may be used as a marker to differentiate renal injury in IgAN patients from healthy individuals. At the same time, according to the estimated glomerular filtration rate (eGFR) and Lee classification of nephropathy, it was determined that with the progression of renal failure and the increase of the pathological grade of kidney tissue, the relative level of miR-33a-5p in kidney tissue also decreased (eGFR <50 ml/min vs. eGFR ≥50 ml/min/1.73 m2 group: 0.38±0.27 vs. 1.00±0.34, P<0.001; Lee grade ≤3 group vs. Lee grade >3: 1.00±0.48 vs. 0.38±0.45, P<0.05). This result suggested that the levels of miR-33a-5p in serum, urine and kidney tissues decreased with the severity of renal injury and the progression of renal failure in patients with IgAN. Hence, miR-33a-5p detected in the serum and urine may be used as a non-invasive biomarker to reflect the progression of renal injury and renal failure in patients with IgAN. [ABSTRACT FROM AUTHOR]