Abstract
Women with severe preeclampsia and HELLP syndrome (sPE/HELLP) are more likely to develop acute kidney injury (AKI) compared to women without sPE/HELLP. AKI during pregnancy is associated with rates of maternal mortality and fetal loss that range from 30-60%. Women with a history of sPE/HELLP are more likely to develop hypertension, and have higher incidences of chronic kidney disease, end stage renal failure and cognitive failure compared to women with histories of normal pregnancies. We tested the hypothesis sPE/HELLP leads to brain damage during pregnancy which is exacerbated by AKI. On gestational day (GD) 12, mini-osmotic pumps infusing sFlt-1 and sEng were placed into rats to induce HELLP. A subset of HELLP and NP rats underwent bilateral renal ischemia-reperfusion surgery for 45 minutes on GD18 to create AKI. After rats had recovered, all rats were placed in metabolic cages for 24hrs. Mean arterial pressure was measured on GD19 followed by Evan’s blue infusion to assess blood brain barrier permeability, or tissue collection and euthanization. During pregnancy HELLP+AKI rats had a significant decrease in urine output compared to NP rats (1.4+0.28 vs. 0.48+ 0.12mL/hr; p=0.01). MAP was significantly increased in HELLP rats (p<0.0001) and HELLP+AKI rats (p=0.03) compared to NP rats. Kidney weight was also significantly increased in NP+AKI compared to NP rats (p=0.005) and in HELLP+AKI compared to HELLP rats (p=0.003). Urine creatinine levels were significantly lower in all groups of rats compared to NP rats (p=0.01). NP pups were significantly larger compared to HELLP (p=0.006), NP+AKI (p=0.0002) and HELLP+AKI (p=0.0005) pups. Rats with HELLP had increased blood brain barrier permeability in the brainstem/cerebellum compared to NP rats (p=0.04). Similar results were seen in NP+AKI (p=0.04) and HELLP+AKI (p=0.01) rats compared to NP rats. Whole brain water weight was significantly increased in HELLP+AKI rats compared to NP rats (p=0.03). The results from the current study suggest that AKI during pregnancy contributes to oliguria, hypertension, decreased urine creatinine, maternal brain injury and reduced pup size. In the setting of HELLP+AKI brain injury was worsened compared to rats with just AKI or HELLP syndrome. Studies are currently ongoing to examine the progression to chronic kidney disease and cognitive failure in rats with a history of sPE/HELLP with and without AKI during pregnancy.
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