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Plasma volume expansion is impaired in pregnancy after recovery from renal ischemia reperfusion injury
Author(s) -
Gillis Ellen,
Sullivan Jennifer
Publication year - 2021
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2021.35.s1.03496
Subject(s) - medicine , pregnancy , renal function , renal ischemia , creatinine , kidney , urology , endocrinology , ischemia , reperfusion injury , biology , genetics
Healthy pregnancy is characterized by plasma volume expansion resulting in a significant increase in renal demands. Low plasma volume expansion during pregnancy is associated with poor fetal outcomes, including intrauterine growth restriction, and is also associated with decreased maternal renal function. Previous studies in our laboratory report that after recovery from renal ischemia reperfusion (IR) injury, female Sprague Dawley rats fail to increase renal function during pregnancy with poor maternal and fetal outcomes. The goal of the current study was to assess plasma volume and renal changes during pregnancy in our model of pregnancy after IR. We hypothesized that plasma volume expansion is impaired in pregnancy in dams after recovery from IR injury. Female Sprague Dawley rats (12 weeks of age, n=4‐6) were randomized to receive either 45 minutes of warm, bilateral renal ischemia or sham surgery. IR injury was confirmed by a significant increase in plasma creatinine 24 hours after surgery (compared to sham controls). Rats were then given one month to recover. Full recovery from IR was confirmed by return of plasma creatinine and urinary protein excretion to baseline levels. Control and IR rats were randomized to either be mated with age‐matched males with pregnancy confirmed by vaginal cytology or serve as virgin controls. Plasma volume was measured during late pregnancy on gestational day 20 by the Evans blue method in the pregnant rats and in age‐matched virgin controls. Kidneys were collected for histological analysis by H&E staining, and glomerular area was measured in 20 glomeruli/kidney. Plasma volume increased during pregnancy in both control and IR dams compared to virgin controls, but the increase was greater in control dams than IR dams (Table, 2‐Way ANOVA, P pregnancy <0.01, P IR <0.01, P Interaction <0.01). Pregnancy also resulted in an increase in glomerular size in both control and IR dams compared to virgin controls, but this increase was also greater in the controls dams (Table, 2‐Way ANOVA, P pregnancy <0.01, P IR =0.01, P Interaction =0.02). These data suggest that despite recovery from IR injury, female rats fail to increase plasma volume in pregnancy along with failure to increase glomerular size. We propose that this failure to increase plasma volume in pregnancy is responsible for the poor fetal outcomes observed in this model. Further studies will examine the mechanisms responsible for plasma volume expansion in pregnancy, and why plasma volume fails to expand after recovery from IR injury.

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