Kidney Week

Abstract: FR-PO0960

Epigenetic Analysis of Kidney Tissue to Elucidate the Pathophysiology of CKD Associated with Preterm Birth and Low Birth Weight

Session Information

• Pediatric Nephrology: Genetic Diseases, Development, Neonatal Nephrology, Glomerular Diseases, and More
  October 23, 2026 | Location: Exhibit Hall A, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Pediatric Nephrology

• 1800 Pediatric Nephrology

Authors

• Ishimori, Shingo, Kobe University Graduate School of Medicine, Kobe, Japan

Shingo Ishimori, MD, PhD

• Fujimura, Junya, Kakogawa Chuo Shimin Byoin, Kakogawa, Hyogo Prefecture, Japan

Junya Fujimura, MD

• Ishiko, Shinya, Takatsuki Byoin, Takatsuki, Osaka Prefecture, Japan

Shinya Ishiko, MD, PhD

• Nishimura, Ryo, Kobe University Graduate School of Medicine, Kobe, Japan

Ryo Nishimura

• Baba, Minato, Kobe University Graduate School of Medicine, Kobe, Japan

Minato Baba

• Fujiwara, Ayako, Kobe University Graduate School of Medicine, Kobe, Japan

Ayako Fujiwara

• Yamamoto, Asahi, Kobe University Graduate School of Medicine, Kobe, Japan

Asahi Yamamoto, MD

• Kimura, Yuka, Kobe University Graduate School of Medicine, Kobe, Japan

Yuka Kimura, MD

• Aoyama, Shuhei, Kobe University Graduate School of Medicine, Kobe, Japan

Shuhei Aoyama, MD

• Ichikawa, Yuta, Kobe University Graduate School of Medicine, Kobe, Japan

Yuta Ichikawa

• Inoki, Yuta, Kobe University Graduate School of Medicine, Kobe, Japan

Yuta Inoki, MD, MEd

• Horinouchi, Tomoko, Kobe University Graduate School of Medicine, Kobe, Japan

Tomoko Horinouchi, MD, PhD

• Yamamura, Tomohiko, Kobe University Graduate School of Medicine, Kobe, Japan

Tomohiko Yamamura, MD, PhD

• Sakakibara, Nana, Kobe University Graduate School of Medicine, Kobe, Japan

Nana Sakakibara, MD, PhD

• Nagano, China, Kobe University Graduate School of Medicine, Kobe, Japan

China Nagano, MD, PhD

• Nozu, Kandai, Kobe University Graduate School of Medicine, Kobe, Japan

Kandai Nozu, MD, PhD

Background

Preterm birth (PB) and low birth weight (LBW) are established risk factors for chronic kidney disease (CKD), primarily through nephron underdevelopment, which is thought to drive tubulointerstitial fibrosis. Postnatal epigenetic alterations could contribute to the progression of PB- and LBW-associated CKD; however, these mechanisms have not yet been evaluated.

Methods

We conducted an epigenome-wide association study using genomic DNA (gDNA) extracted from 16 kidney biopsy specimens (8 cases of PB- and LBW-associated CKD and 8 controls). DNA methylation across more than 900,000 CpG sites was analyzed.

Results

Only two DMRs showing hypermethylation with a Δβ value > 0.05 were detected at a false discovery rate < 0.05: OSBPL8, which encodes a protein involved in lipid transport and intermembrane lipid exchange, and SHISA5, which encodes a protein that mediates endoplasmic reticulum (ER) stress responses and apoptosis (Fig. 1). The DMR in OSBPL8 was located within intron 1 and was annotated as an enhancer-like signature, whereas the DMR in SHISA5 was located in the promoter region 1–2 kb upstream of the transcription start site. In epigenetic clock analysis using gDNA derived from kidney specimens, an earlier gestational age was significantly associated with increased HorvathAge estimator acceleration (Fig. 2). p16^INK4a immunostaining for the evaluation of cellular senescence was predominantly detected in the distal tubules of children with PB- and LBW-associated CKD (Fig. 3).

Conclusion

Hypermethylation of the enhancer-like signature in OSBPL8 may lead to impaired intracellular lipid transport and lipotoxicity, whereas hypermethylation of the promoter region in SHISA5 may result in decreased tolerance to ER stress. Consequently, PB and LBW may predispose the kidney to functional impairment by rendering tubular cells vulnerable to chronic stress through epigenetically mediated processes that promote aging and cellular senescence.