Abstract 123: Female Rats With History Of Acute Kidney Injury Develop Endothelial Dysfunction, Increased Renal Inflammation And Decreased Aldosterone During Pregnancy

Abstract

Clinical data report a 3-5 fold increase in adverse pregnancy outcomes among women with prior acute kidney injury (AKI), despite clinical recovery of renal function (creatinine clearance) before pregnancy. We showed that female Sprague-Dawley (SD) rats with recovered renal function from bilateral renal ischemia-reperfusion (AKI) develop decreased creatinine clearance, increased uterine artery resistance and decreased fetal growth in pregnancy via mechanisms unknown. We tested the hypothesis that AKI prior to pregnancy induces endothelial dysfunction, renal inflammation and dysregulated renin-angiotensin aldosterone system (RAAS) activation. Female SD rats received either 45-minute AKI or sham surgery and mated after 30 days (N=9 Sham, N=10 AKI). Gestation day 1 (GD1) was identified through vaginal smear and on GD19, rats were placed in metabolic cages before sacrificed on GD20 for plasma and tissue collection. Vascular function was assessed via wire myography on 3 rd order mesenteric arteries while renal inflammation was quantified via flow cytometry. Pre-pregnancy AKI reduced endothelial-dependent relaxation to acetylcholine (ACh) compared to sham (concentration-response, 1nM-10uM range, 2-way ANOVA, RM, *P<0.05), indicating endothelial dysfunction. LNAME incubation ablated ACh-mediated relaxation equivocally in post-AKI and sham rats, indicating AKI induces a non-NO mediated endothelial dysfunction. Renal CD3+ T cells increased (4.4±0.23 vs 2.4±0.14%Total Renal Cells, *P<0.05) while renal IL-10 decreased (3.0±0.8 vs 12.4±2.2%CD3+ T cells) in post-AKI pregnant rats compared to sham. Urinary volume/day (29.6±5 vs 18.6±2 ml/day, *P<0.05), water intake (54.7±5 vs 40.6±1 ml/day*P<0.05) and kidney weight (2.777±0.3/mg/g vs 2.4245±0.3) increased in post-AKI pregnant rats compared to sham. In addition, urinary aldosterone levels measured by ELISA decreased in post-AKI pregnant rats compared to sham (188±34 vs 312±35 pg/ml/day, *P<0.05), suggesting disruption of fluid homeostasis and RAAS by pre-pregnancy AKI. Collectively, these data indicate that AKI prior to conception induces endothelial dysfunction, increases renal inflammation and decreases RAAS activation in pregnancy.