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

Pediatr Res. 2015 Dec;78(6):678-82. doi: 10.1038/pr.2015.153. Epub 2015 Aug 13.

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.

MeSH terms

  • Age Factors
  • Angiotensinogen / metabolism*
  • Angiotensinogen / urine
  • Animals
  • Biomarkers / urine
  • Birth Weight
  • Creatinine / urine
  • Disease Models, Animal
  • Early Diagnosis
  • Female
  • Fetal Growth Retardation / diagnosis
  • Fetal Growth Retardation / etiology
  • Fetal Growth Retardation / genetics
  • Fetal Growth Retardation / metabolism*
  • Fetal Growth Retardation / physiopathology
  • Kidney / metabolism*
  • Kidney / pathology
  • Kidney / physiopathology
  • Kidney Diseases / diagnosis
  • Kidney Diseases / etiology
  • Kidney Diseases / genetics
  • Kidney Diseases / metabolism*
  • Kidney Diseases / physiopathology
  • Ligation
  • Organ Size
  • Predictive Value of Tests
  • Pregnancy
  • Prenatal Exposure Delayed Effects
  • Proteinuria / etiology
  • Proteinuria / metabolism
  • Proteinuria / physiopathology
  • Rats, Sprague-Dawley
  • Renin-Angiotensin System
  • Up-Regulation
  • Uterine Artery / surgery

Substances

  • Agt protein, rat
  • Biomarkers
  • Angiotensinogen
  • Creatinine