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Abstract: SA-OR108

Novel Experimental Model of Poor Pregnancy Outcomes After Recovery from Ischemia-Reperfusion Injury

Session Information

Category: Women’s Health and Kidney Diseases

  • 2000 Women’s Health and Kidney Diseases

Authors

  • Gillis, Ellen Elizabeth, Augusta University, Augusta, Georgia, United States
  • Sullivan, Jennifer C., Augusta University, Evans, Georgia, United States
Background

Recent clinical studies have reported that women with a history of acute kidney injury (AKI) have a greater incidence of maternal and fetal adverse outcomes during pregnancy, despite fully recovering renal function prior to conception. The mechanisms contributing to these adverse outcomes in pregnancy after AKI are not yet understood. In the current study, a rodent model of recovered AKI (r-AKI) was developed in an effort to elucidate the mechanisms contributing to adverse pregnancy outcomes after AKI. We hypothesize that female Sprague Dawley (SD) rats will have poor pregnancy outcomes after recovery from ischemia reperfusion (IR) injury, our experimental model of AKI.

Methods

IR surgery was performed on female SD rats (10 wks age) by clamping both renal arteries for 45 minutes. Rats were then allowed to recover for 1 month before they were mated. Recovery from IR was confirmed by plasma creatinine and urinary protein excretion (UPE). Vaginal smears were performed daily once mating began, with sperm on the slide indicative of day 1 of pregnancy. Rats were then sacrificed during late pregnancy on gestational day 20.

Results

UPE, a crude marker of renal injury, was significantly higher in r-AKI dams in late pregnancy (Table, *p<0.05, T-test). r-AKI dams also had significantly higher plasma creatinine and urea levels than control dams, suggesting that subclinical injury after IR leaves these dams unable to handle the hemodynamic changes in pregnancy, resulting in renal insufficiency (Table). In addition to adverse maternal outcomes, fetal outcomes were also significantly worse in r-AKI dams, as measured by decreases in fetal weight and an increase in fetal death (Table).

Conclusion

Pregnancy after recovery from AKI resulted in maternal renal insufficiency and significant impairments in fetal growth in the current study. This mimics what has recently been reported in the clinical population, indicating that this model is a useful tool to further explore the alterations in kidney function after AKI in females. Ongoing studies in the lab are further exploring the maternal syndrome in these rats, focusing on alterations in renal immune cells.

 UPE (mg/d)Plasma Creatinine (mg/dL)Plasma Urea (mg/dL)Pup Weight (g)Fetal Death (%)
Control4.2±0.660.25±0.0133.0±0.574.0±0.080
r-AKI18.4±0.61*0.37±0.01*40.8±0.44*2.3±0.03*10.3±5.7*

Funding

  • Other NIH Support