TY - JOUR
T1 - Adverse maternal and fetal outcomes in a novel experimental model of pregnancy after recovery from renal ischemia-reperfusion injury
AU - Gillis, Ellen E.
AU - Brands, Michael W.
AU - Sullivan, Jennifer C.
N1 - Publisher Copyright:
Copyright © 2021 by the American Society of Nephrology.
PY - 2021/2
Y1 - 2021/2
N2 - Background Recent clinical studies report that women with a history of AKI have an increased incidence of maternal and fetal adverse outcomes during pregnancy, despite fully recovering renal function prior to conception. The mechanisms contributing to such adverse outcomes in pregnancy after AKI are not yet understood. Methods To develop a rodent model to investigate fetal and maternal outcomes in female animals with a history of AKI, we used ischemia-reperfusion injury as an experimental model of AKI in female Sprague Dawley rats. The 12-week-old animals underwent warm bilateral ischemia-reperfusion surgery involving clamping of both renal arteries for 45 minutes or sham surgery (control). Rats were allowed to recover for 1 month prior to mating. Recovery from ischemia-reperfusion injury was confirmed by measurements of plasma creatinine and urinary protein excretion. We assessed maternal and fetal outcomes during late pregnancy on gestational day 20. Results After recovery from ischemia-reperfusion injury, compared with healthy sham-surgery controls, dams exhibited pregnancy-induced renal insufficiency with increases in plasma creatinine and urea, along with increased urinary protein excretion. Additionally, recovered ischemia-reperfusion dams experienced worse fetal outcomes compared with controls, with intrauterine growth restriction leading to higher rates of fetal demise and smaller pups. Conclusions In this rat model, despite biochemical resolution of ischemia-reperfusion injury, subsequent pregnancy resulted in maternal renal insufficiency and significant impairments in fetal growth. This mirrors findings in recent reports in the clinical population, indicating that this model may be a useful tool to further explore the alterations in kidney function after AKI in women.
AB - Background Recent clinical studies report that women with a history of AKI have an increased incidence of maternal and fetal adverse outcomes during pregnancy, despite fully recovering renal function prior to conception. The mechanisms contributing to such adverse outcomes in pregnancy after AKI are not yet understood. Methods To develop a rodent model to investigate fetal and maternal outcomes in female animals with a history of AKI, we used ischemia-reperfusion injury as an experimental model of AKI in female Sprague Dawley rats. The 12-week-old animals underwent warm bilateral ischemia-reperfusion surgery involving clamping of both renal arteries for 45 minutes or sham surgery (control). Rats were allowed to recover for 1 month prior to mating. Recovery from ischemia-reperfusion injury was confirmed by measurements of plasma creatinine and urinary protein excretion. We assessed maternal and fetal outcomes during late pregnancy on gestational day 20. Results After recovery from ischemia-reperfusion injury, compared with healthy sham-surgery controls, dams exhibited pregnancy-induced renal insufficiency with increases in plasma creatinine and urea, along with increased urinary protein excretion. Additionally, recovered ischemia-reperfusion dams experienced worse fetal outcomes compared with controls, with intrauterine growth restriction leading to higher rates of fetal demise and smaller pups. Conclusions In this rat model, despite biochemical resolution of ischemia-reperfusion injury, subsequent pregnancy resulted in maternal renal insufficiency and significant impairments in fetal growth. This mirrors findings in recent reports in the clinical population, indicating that this model may be a useful tool to further explore the alterations in kidney function after AKI in women.
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U2 - 10.1681/ASN.2020020127
DO - 10.1681/ASN.2020020127
M3 - Article
C2 - 33408137
AN - SCOPUS:85100339534
SN - 1046-6673
VL - 32
SP - 375
EP - 384
JO - Journal of the American Society of Nephrology
JF - Journal of the American Society of Nephrology
IS - 2
ER -