Abstract
AKI during pregnancy is associated with high rates of maternal morbidity/mortality as well as fetal loss. Unfortunately women with HELLP (hemolysis, elevated liver, and low platelet) syndrome and preeclampsia are at an increased risk of developing AKI. For most women AKI during pregnancy resolves shortly after pregnancy and the effects have been thought to be temporary. However, new reports suggest that AKI during pregnancy can lead to progression of CKD. Using an established animal model of HELLP syndrome, the objective of the current study was to determine if AKI during pregnancy was associated with hypertension in the post-partum period. On gestational day (GD) 12, mini-osmotic pumps infusing sFlt-1 and sEng were placed into rats to induce HELLP (n=12). A subset of HELLP (n=7) and normal pregnant (NP; n=6) rats underwent bilateral renal ischemia-reperfusion surgery for 45 minutes on GD18. Untreated NP rats served as controls (n=9). All rats delivered on GD21 and were euthanized at post-partum week (PPW) 15. HELLP (6.2±0.08g; p=0.04), NP+AKI (5.3±0.09g; p<0.01) and HELLP+AKI (5.8±0.11g; p<0.01) rat pups were significantly smaller compared to NP rat pups (6.6±0.06g). Blood pressure was significantly increased in NP+AKI rats compared to NP rats (146±3.2 vs. 137±3.9mmHg; p=0.05) and in HELLP compared to NP rats (159±6.2mmHg; p=0.01) at PPW13. GFR was not increased in HELLP compared to NP (p=0.06) but was increased in NP+AKI rats (p=0.03) when measured at PPW14. Immune cells were examined via flow cytometry and NP+AKI had increased infiltrating renal CD4 + T cells compared to NP rats (11.2% vs. 3.4%; p=0.04). The ratio of M1/M2 macrophages in the kidneys of NP+AKI (19.2%; p=0.01) and HELLP (5.9%; p=0.05) was increased compared to NP rats (2.7%). Currently there are only 2 HELLP+AKI rats that survived to PPW13 (p=0.008) as 71.5% of the group died prior to post-partum day 5. The results from this study suggest that AKI during pregnancy contributes to progressive kidney injury and immune cell infiltration into the kidney. Additionally both NP+AKI and HELLP rats remained hypertensive 3 months post-partum. These results suggest that the cardiovascular and renal affects that occur during pregnancy can have a chronic affect and contribute to the worsening of maternal health.
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