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Glomerulonephritis and Immunologic Disorders

Urinary exosomal miRNA-451a can be used as a potential noninvasive biomarker for diagnosis, reflecting tubulointerstitial damage and therapeutic response in IgA nephropathy

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Article: 2319326 | Received 27 Sep 2023, Accepted 09 Feb 2024, Published online: 20 Feb 2024
 

Abstract

To investigate the potential clinical value of urinary exosomal (uE) miR-451a as a biomarker for IgAN, urinary exosomes were isolated from 40 patients with IgAN, 30 patients with primary renal diseases without IgA as disease controls (non-IgAN group) and 21 healthy controls (HCs). The expression of miR-451a within exosomes was examined by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). uE miR-451a was significantly upregulated in patients with IgAN compared to non-IgAN and HCs. The uE miR-451a level was positively correlated with the change in eGFR and negatively correlated with serum creatinine, urinary macrophage migration inhibitory factor (MIF), interleukin-6 (IL-6) and tumor necrosis factor (TNF-α). A dual-luciferase reporter assay confirmed that MIF was a direct target of miR-451a. Receiver operating characteristic (ROC) curve analysis revealed that the expression of uE miR-451a showed potential diagnostic value for IgAN. Additionally, the uE miR-451a level could distinguish patients with IgAN with mild tubular atrophy/interstitial fibrosis from those with severe tubular atrophy/interstitial fibrosis. After a mean follow-up of 14.2 months, the levels of eGFR loss (ml/min/1.73 m2/year) were negatively correlated with baseline miR-451a. The levels of baseline miR-451a in the complete remission group were significantly higher than those in the non-complete remission group. uE miR-451a expression was significantly elevated in patients with IgA nephropathy and may serve as a potential biomarker for the diagnosis of IgAN and evaluation of tubulointerstitial damage, while the baseline levels of uE miR-451a may be predictors of therapeutic efficacy and disease progression.

Acknowledgments

We thank LetPub (www.letpub.com) for its linguistic assistance during the preparation of this manuscript.

Authors’ contributions

Conception and design of the work: QZ; Data collection: QZ, YZ, HZH, XLH, YKL, and YZ; Supervision: QZ; Analysis and interpretation of the data: QZ, YZ, HZH, XLH, and YKL; Statistical analysis: QZ and YZ; Drafting the manuscript: QZ; Critical revision of the manuscript: all authors. All authors contributed to the article and approved the submitted version.

Consent to publish

The manuscript has been read and approved for submission by all (co-)authors.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Ethical approval

This study was conducted in accordance with the ethical principles stated in the Declaration of Helsinki and was approved by the ethics committee of Shanxi Provincial People’s Hospital (reference numbers: (2021) Shanxi Medical Ethics Review No. 32). The patients/participants provided their written informed consent to participate in this study.

Patient consent

All participants provided their written informed consent to participate in this study.

Date availability statement

The original contributions presented in this study are included in the article material. Further inquiries may be directed to the corresponding author.

Additional information

Funding

This work was financially supported by the Four Batches of Scientific Research Projects of Shanxi Provincial Health Commission (No: 2021XM29) and the Central Guiding Local Science and Technology Development Fund Project (No: YDZJSX2021B014). Naturel Science Foundation of Shanxi Province; Innovative Project of Postgraduate Education in Shanxi Province.