Acute Kidney Injury During Pregnancy Leads to Memory Impairment but not Anxiety in Rats with a History of Severe Preeclampsia/HELLP Syndrome
Authors: Griffin Ashley , Bowles Teylor , Robinson Reanna , Szczepanski Jamie , Spencer Shauna-Kay , Williams Jan , Dumas John Polk , Shaffery James , Wallace Kedra 
Published: April 2020

OBJECTIVE

Women with hypertensive conditions of pregnancy such as severe PE (preeclampsia)/HELLP (hemolysis, elevated liver enzyme, and low platelets) syndrome are at an increased risk of developing Acute Kidney Injury (AKI). New reports suggest that AKI during pregnancy can lead to the progression of chronic kidney disease (CKD). Between 27–67% of patients with CKD have evidence of depression, cognitive impairment and dementia that is directly linked to renal damage. Among these deficits are impairments in memory, orientation, reasoning and executive function. Incidentally, women with a history of hypertensive disorders with and without AKI have an increased risk of developing mental health and cognitive disorders. Using an established animal model of severe PE/HELLP syndrome we sought to test the hypothesis that AKI in the presence of severe PE/HELLP exacerbates cognitive impairment and anxiety in the postpartum period.

STUDY DESIGN

On gestational day (GD) 12, sFlt‐1 and sEng was infused via mini‐osmotic pump into the abdominal space of timed‐pregnant Sprague Dawley rats to induce severe PE/HELLP. A subset of HELLP and normal pregnant (NP) rats underwent bilateral renal ischemia‐reperfusion surgery for 45 minutes on GD18 to induce AKI. All rats delivered on GD21, underwent behavioral testing between postpartum weeks (PPW) 11–13 and were euthanized at PPW15. FITC‐sinistrin which was used to assess glomerular filtration (measure of kidney function), blood pressure via carotid catheter, and urinary creatinine were all measured during PPW15. N’s per group = 7 –10.

RESULTS

Compared to NP rats (p=0.01), HELLP, NP+AKI and HELLP+AKI rats had significant impairments in learning and memory. HELLP rats spent significantly less time in the open arms of the zero maze compared to NP (p=0.04) and NP+AKI (p=0.04). The time in open arms for HELLP+AKI rats were significantly less, as well, compared to NP (p=0.01) and NP+AKI (p=0.01) rats. Kidney function significantly declined in H+AKI (p= 0.001) and NP+AKI (p=0.009) rats compared to NP rats, as well as HELLP+AKI (p=0.03) rats compared to HELLP rats. Urinary creatinine was significantly increased in HELLP+AKI rats compared to NP (p=0.03) and HELLP (p=0.007) rats as well as NP+AKI (p=0.01) rats to HELLP rats. Blood pressure was significantly increased in NP+AKI (p=0.003), HELLP+AKI (p=0.0007), and HELLP (p=0.02) rats compared to NP rats.

CONCLUSION

The results from this study suggest that HELLP during pregnancy impairs learning and memory and is exacerbated by AKI. Anxiety was only impaired in rats with a history of severe PE/HELLP with/without AKI suggesting that renal injury may lead to selective psychological impairments. Hypertension persisted into the post‐partum period for rats with a history of severe PE/HELLP. Renal function wasn’t recovered into the post‐partum period for rats with history of AKI.

Support or Funding Information

This work was sponsored by P20GM121334 and the UMMC Office of Sponsored Program.