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Urinary exosomal circular RNAs of sex chromosome origin are associated with gender-related risk differences of clinicopathological features in patients with IgA nephropathy

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Abstract

Background

There are arguments for individualized treatments and the necessity of non-invasive biomarkers for patients with IgA nephropathy (IgAN) according to gender, but the rationale remains unclear. We aimed to investigate the relationship between urine exosomal circular RNA (circRNA) levels, related genes, clinical features, and renal pathological features in IgA nephropathy patients of different genders.

Methods

Clinicopathological data from patients of different genders from a multicenter cohort were retrospectively analyzed. We used the Oxford classification to examine the severity of pathological damage in these patients. We compared clinical features and renal pathologies between IgAN patients of different genders. Using findings of urine exosomal circRNAs from male IgAN patients, we analyzed the relationship between this factor, the regulated genes located on the sex chromosomes, and renal pathologies.

Results

A total of 502 IgAN patients were included. The proportion of male patients with crescent formation was higher than that of females (p = 0.019). Multivariate logistic regression analysis showed that proteinuria was an independent marker for crescent formation in male and female patients with IgAN, while smoking and higher low-density lipoprotein cholesterol (LDL-C) levels were independent risk factors for crescent formation in males alone. Urine exosomal circRNA chrY:15478147-15481229- located on the Y chromosome in male patients was negatively correlated with the expressions of UTY in specific regions of the Y chromosome.

Conclusion

Compared with female patients, males with IgAN had more severe renal dysfunction and a higher probability of glomerular crescent formation. Urine exosomal circRNA chrY:15478147-15481229- might participate in the pathogenesis of IgAN in male patients by altering UTY expressions.

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Data availability

All data generated or analyzed during this study are included in this article.

Code availability

Not applicable.

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Funding

This study was supported by the Hygiene and Health Technology Innovation Project of Health Commission of Jilin Province (No. 2020J037).

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Author notes

  1. Rumei Luan and Geng Tian contributed equally to this work.

Authors and Affiliations

  1. Department of Nephrology, The Second Hospital of Jilin University, 218 Ziqiang Street, Changchun, 130041, Jilin, China

    Rumei Luan, Hong Zhang, Xiaolei Shi, Jicui Li & Xuehong Lu

  2. Department of Gynaecology and Obstetrics, The Second Hospital of Jilin University, Changchun, 130041, China

    Geng Tian

  3. Department of Nephrology, The People’s Hospital of Jilin Province, Changchun, 130012, China

    Rui Zhang

Authors
  1. Rumei Luan
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  2. Geng Tian
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  4. Xiaolei Shi
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Contributions

LRM and TG carried out the experiment and wrote the paper. ZH analyzed the clinical data. SXL and ZR collected the clinical data. LJC collected urine samples. LXH conceived the research idea and analyzed the experimental data. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Xuehong Lu.

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The authors report no conflict of interest.

Ethical approval

The current study was approved by the Ethics Committee of the Second Hospital of Jilin University (No.2020001) and adhered to the Helsinki Declaration guidelines.

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Luan, R., Tian, G., Zhang, H. et al. Urinary exosomal circular RNAs of sex chromosome origin are associated with gender-related risk differences of clinicopathological features in patients with IgA nephropathy. J Nephrol 35, 1069–1078 (2022). https://doi.org/10.1007/s40620-021-01118-7

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  • DOI: https://doi.org/10.1007/s40620-021-01118-7

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