Kidney Week

Abstract: FR-PO931

The Transcriptomic Landscape of microRNAs Encapsulated in Circulating Extracellular Vesicles and CKD Progression in Japanese Adults

Session Information

• CKD Epidemiology, Risk Factors, Prevention - II
  November 03, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: CKD (Non-Dialysis)

• 2301 CKD (Non-Dialysis): Epidemiology, Risk Factors, and Prevention

Authors

• Inaba, Shunsuke, Department of Nephrology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo, Japan

Shunsuke Inaba,

• Mandai, Shintaro, Department of Nephrology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo, Japan

Shintaro Mandai,

• Nakano, Yuta, Department of Nephrology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo, Japan

Yuta Nakano,

• Matsuki, Hisazumi, Department of Nephrology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo, Japan

Hisazumi Matsuki,

• Fujiki, Tamami, Department of Nephrology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo, Japan

Tamami Fujiki,

• Mori, Yutaro, Department of Nephrology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo, Japan

Yutaro Mori,

• Ando, Fumiaki, Department of Nephrology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo, Japan

Fumiaki Ando,

• Mori, Takayasu, Department of Nephrology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo, Japan

Takayasu Mori,

• Susa, Koichiro, Department of Nephrology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo, Japan

Koichiro Susa,

• Iimori, Soichiro, Department of Nephrology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo, Japan

Soichiro Iimori,

• Naito, Shotaro, Department of Nephrology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo, Japan

Shotaro Naito,

• Sohara, Eisei, Department of Nephrology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo, Japan

Eisei Sohara,

• Uchida, Shinichi, Department of Nephrology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo, Japan

Shinichi Uchida,

Background

The global economic burden of chronic kidney disease (CKD) and end-stage-kidney disease (ESKD) is still increasing. However, non-invasive techniques to predict CKD progression have yet to be established. This study aimed to determine circulating small extracellular vesicle (cEV)-encapsulated miRNAs predictive of kidney outcome in patients with CKD.

Methods

We enrolled 36 Japanese adults with non-dialysis-dependent CKD patients from the previously published cohort studies. We performed miRNA transcriptomic analyses using cEVs extracted from the serum of the participants. The patients were followed up until death, transfer, or ESKD requiring dialysis. The correlation between miRNA expressions and baseline eGFR was examined with the linear regression model. A stratified Cox regression model was used to assess the risk of a kidney composite outcome including ESKD or 30% eGFR reduction. We also performed the logistic regression analysis to examine the risk of rapid eGFR decline, which was defined as eGFR reduction <-5 mL/min/1.73 m²/year or dialysis initiation within a follow-up of six months. All analyses were adjusted for potential confounders including age, sex, diabetes mellitus, and cardiovascular disease.

Results

The median age of the participants was 71 years (interquartile range, 61-79), 25% was female, and the median baseline eGFR was 31 (21-53) mL/min/1.73 m². After a median follow-up period of 636 days, the kidney composite outcome and rapid eGFR decline occurred in 16 and 16 patients, respectively. Among 2578 miRNAs identified, all three criteria including the negative association between miRNA expression levels and baseline eGFR (P < 0.1), increased hazards ratios for a risk of the kidney composite outcome (HR ≥ 1.5; P < 0.05), and increased odds ratios (ORs) for a risk of rapid eGFR decline (OR ≥ 1.5; P < 0.1) were met for three miRNAs. The KEGG molecular pathways associated with miRNA target molecules found ubiquitin-mediated proteolysis, Hippo signaling pathway, protein processing in endoplasmic reticulum, and MAPK signaling pathway.

Conclusion

This study uncovered miRNA signature encapsulated in cEVs that is strongly associated with a risk of CKD progression in adults.

Funding

• Private Foundation Support