Ps-bpb06-6: renal injury associated with arginine vasopressin induction in a rat model of preeclampsia

Objective: Worldwide, preeclampsia (PE) accounts for 2–8% of pregnancies and is a main cause of maternal and fetal morbidity and mortality. In vivo murine studies confirm the use of arginine vasopressin (AVP) in replicating the clinical symptoms of PE development, suggestive of a role for PE prediction. The renal effects that AVP may have in PE remains elusive, hence this study aimed to explore the physiological effects of AVP on the kidneys of pregnant rats in an effort to determine its role in PE development. Design and method: Twenty-four female Sprague Dawley rats (non-pregnant saline, pregnant saline, non-pregnant AVP and pregnant AVP) were surgically implanted with ALZET mini osmotic pumps infusing with either saline or AVP for 18 days. Blood pressure measurements and urine samples were taken on gestational days (GD) 8, 14 and 18. Placental and fetal weights were recorded following sacrifice on GD18. Urinary levels of kidney injury molecule-1 (KIM-1) were determined using the rat kidney toxicity immunoassay panel 1 (#RKTX1MAG-37K). Immunohistochemistry was used to determine the expression of KIM-1 in rat kidney tissue. Results: Systolic [143.00 (139.67–144.00) mmHg vs 125.00 (124.00–127.00) mmHg; p < 0.05] and diastolic blood pressures [103.50 (100.33–106.88) mmHg vs 81.00 (80.00–87.00) mmHg; p < 0.001] were significantly higher in the pregnant AVP vs pregnant saline group. Urinary protein levels in pregnant AVP rats [0.45 (0.42–0.48) g/L] were significantly elevated in comparison to pregnant saline rats [0.24 (0.21–0.32) g/L; p < 0.05]. Pregnant AVP rats also demonstrated a significant decrease in individual placental [0.39 (0.31–0.46) g v s 0.59 (0.55–0.63) g; p < 0.05] and pup weights [1.57 (1.45–1.67) g vs 1.79 (1.70–1.85) g; p < 0.05] in comparison to pregnant saline rats. Urinary KIM-1 levels are significantly elevated in the pregnant AVP (0.53 ± 0.05 ng/mL) vs pregnant saline group (0.17 ± 0.02 ng/mL; p < 0.001). Qualitative analysis revealed that KIM-1 expression is markedly upregulated on the apical membrane surface of epithelial cells of the proximal convoluted tubules in AVP treated rats. Conclusions: AVP infusion increases blood pressure, urine protein levels and urinary and tissue expression of KIM-1. Our findings indicate that there is significant kidney injury associated with AVP treatment, indicative of the utility of this model in studying the mechanisms driving renal damage in PE.