Abstract
Background:
Few studies have addressed the growing concerns of chronic kidney diseases in children with intrauterine growth restriction (IUGR). Therefore, the purpose of this study was to evaluate long-term kidney dysfunction and determine if urinary angiotensinogen (AGT) was suitable as a novel early biomarker for kidney dysfunction in IUGR offspring.
Methods:
Pregnant rats underwent bilateral uterine artery ligation, and as a control group, sham surgeries were performed.
Results:
The birth weight was reduced, the urinary AGT to creatinine ratio was significantly higher at week 20, and urinary protein levels were significantly higher at week 32 in IUGR rats than in control rats. On the other hand, the histological findings at week 32 revealed long-term kidney dysfunction, more severe glomerulosclerosis, and greater glomerular diameters in IUGR rats. Moreover, AGT mRNA expression and immunohistological staining were significantly increased in IUGR rats; this suggests that the intrarenal renin–angiotensin system (RAS) contributes to renal dysfunction of IUGR offspring.
Conclusion:
Urinary AGT elevation prior to urinary protein levels suggests that AGT is an early biomarker. At week 32, kidney dysfunction was severe in IUGR rats and intrarenal RAS appeared to be one of the causes.
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Acknowledgements
The authors thank Yumiko Sakurai, of the Department of Pediatrics and Adolescent Medicine, Juntendo University; Tomomi Ikeda; and Takako Ikegami of the Division of Molecular and Biochemical Research, Biomedical Research Center, Juntendo University Graduate School of Medicine; Yuuko Kojima and Shinji Nakamura, of the Division of Biomedical Imaging Research, Juntendo University Graduate School of Medicine, for their extended technical support; and Takeshi Asakura and Enago (www.enago.jp) for the English language review for detailed and precise advice related to the writing of this article.
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Murano, Y., Nishizaki, N., Endo, A. et al. Evaluation of kidney dysfunction and angiotensinogen as an early novel biomarker of intrauterine growth restricted offspring rats. Pediatr Res 78, 678–682 (2015). https://doi.org/10.1038/pr.2015.153
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DOI: https://doi.org/10.1038/pr.2015.153
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