Kidney Week

Abstract: FR-PO682

Role of Angiotensinogen in Children with a History of Preterm Birth and Nephron Hypertrophy

Session Information

• Pediatric Nephrology - 1
  October 25, 2024 | Location: Exhibit Hall, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Pediatric Nephrology

• 1900 Pediatric Nephrology

Authors

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

Shingo Ishimori, MD, PhD

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

Yuka Kimura

• Kitakado, Hideaki, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan

Hideaki Kitakado, MD

• Ueda, Chika, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan

Chika Ueda, MD

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

Yuta Inoki, MD

• Tanaka, Yu, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan

Yu Tanaka, MD

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

Junya Fujimura, MD

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

Tomoko Horinouchi, MD, PhD

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

Tomohiko Yamamura, MD, PhD

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

Nana Sakakibara, MD, PhD

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

China Nagano, MD, PhD

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

Kandai Nozu, MD, PhD

Background

A history of preterm birth and low birth weight (preterm) is a risk factor for chronic kidney disease, which is primarily characterized by tubulointerstitial damage resulting from a decrease in nephron number and compensatory nephron hypertrophy (NH). While the renin–angiotensin system (RAS) plays a crucial role in renal development, no pathological studies have examined the association between RAS and tubulointerstitial lesions in children with a history of preterm birth.

Methods

We performed immunohistochemical staining of renal biopsy specimens collected from 2000 to 2023. Patients were eligible if they had pathological minimal change (MC) or NH without other types of nephritis, and if the indication for renal biopsy was asymptomatic proteinuria, nephrotic syndrome, or decreased renal function. Immunohistochemical staining of angiotensinogen (AGT) was used as a marker of intrarenal RAS, and angiotensin II was used as a marker of systemic RAS.

Results

We enrolled 36 children with a median age at the renal biopsy of 13.4 years. AGT staining was negative in the glomeruli of children with NH but positive in the renal tubules (Fig. a). The positive area of AGT staining in the renal tubules was significantly correlated with an increase in the average area of a single glomerulus (p<0.01, Fig. b). The positive area of AGT staining in the renal tubules of preterm children with NH (n=8), full-term children with NH (n=5), and preterm children with MC (n=5) was significantly more extensive than that in full-term children with MC (n=18) (65.8, 153.2, and 53.0 μm² vs 19.4 μm², all p<0.01; Fig. c). Angiotensin II staining was weakly positive in the renal tubules across all four groups, with no significant difference between the groups.

Conclusion

AGT may play a major role as an indicator of intrarenal RAS in preterm children even before the onset of NH.