Evaluation of kidney dysfunction and angiotensinogen as an early novel biomarker of intrauterine growth restricted offspring rats.
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.


CONCLUSIONS
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.
Department of Pediatrics and Adolescent Medicine, Juntendo University Graduate School of Medicine, Tokyo, Japan.
Yayoi
Y
Murano
Department of Pediatrics and Adolescent Medicine, Juntendo University Faculty of Medicine, Tokyo, Japan.
Naoto
N
Nishizaki
Department of Pediatrics and Adolescent Medicine, Juntendo University Faculty of Medicine, Tokyo, Japan.
Amane
A
Endo
Department of Pediatrics and Adolescent Medicine, Juntendo University Graduate School of Medicine, Tokyo, Japan.
Naho
N
Ikeda
Department of Pediatrics and Adolescent Medicine, Juntendo University Faculty of Medicine, Tokyo, Japan.
Tomonosuke
T
Someya
Department of Pediatrics and Adolescent Medicine, Juntendo University Graduate School of Medicine, Tokyo, Japan.
Mayu
M
Nakagawa
Department of Pediatrics and Adolescent Medicine, Juntendo University Graduate School of Medicine, Tokyo, Japan.
Taichi
T
Hara
Division of Nephrology, Saitama Children's Medical Center, Saitama, Japan.
Koji
K
Sakuraya
Department of Pediatrics and Adolescent Medicine, Juntendo University Faculty of Medicine, Tokyo, Japan.
Satoshi
S
Hara
Department of Pediatrics, The Jikei University School of Medicine, Tokyo, Japan.
Daishi
D
Hirano
Department of Pediatrics and Adolescent Medicine, Juntendo University Graduate School of Medicine, Tokyo, Japan.
Mitsuyoshi
M
Suzuki
Department of Pediatrics and Adolescent Medicine, Juntendo University Graduate School of Medicine, Tokyo, Japan.
Hiromichi
H
Shoji
Department of Pediatrics, The Jikei University School of Medicine, Tokyo, Japan.
Shuichiro
S
Fujinaga
Department of Pediatrics and Adolescent Medicine, Juntendo University Faculty of Medicine, Tokyo, Japan.
Yoshiyuki
Y
Ohtomo
Department of Pediatrics and Adolescent Medicine, Juntendo University Graduate School of Medicine, Tokyo, Japan.
Toshiaki
T
Shimizu
D000367:Age Factors; D000808:Angiotensinogen / Q000378:metabolism* / Q000652:urine; D000818:Animals; D015415:Biomarkers / Q000652:urine; D001724:Birth Weight; D003404:Creatinine / Q000652:urine; D004195:Disease Models, Animal; D042241:Early Diagnosis; D005260:Female; D005317:Fetal Growth Retardation / Q000175:diagnosis / Q000209:etiology / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D007668:Kidney / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D007674:Kidney Diseases / Q000175:diagnosis / Q000209:etiology / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D008026:Ligation; D009929:Organ Size; D011237:Predictive Value of Tests; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D011507:Proteinuria / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology; D017207:Rats, Sprague-Dawley; D012084:Renin-Angiotensin System; D015854:Up-Regulation; D055988:Uterine Artery / Q000601:surgery
C534933:Agt protein, rat; D015415:Biomarkers; D000808:Angiotensinogen; D003404:Creatinine