O14. Is preeclampsia a variant of Liddles syndrome with enhanced activity of the epithelial sodium channel in the kidneys?

Abstract

Introduction Preeclampsia is characterized by hypertension accompanied by proteinuria. The plasma protease plasmin is aberrantly filtered to pre-urine in preeclampsia and may activate the epithelial sodium channel ENaC in the renal collecting ducts. This mechanism could contribute to impaired sodium excretion, suppression of renin–angiotensin–aldosterone and hypertension which are features of preeclampsia. Objectives It was hypothesized that established hypertension of pregnancy/preeclampsia share features with Liddles syndrome and display hyper-active ENaC and therefore blood pressure is more sensitive to NaCl intake compared to normal pregnancy whereas the renin–angiotensin–aldosterone system is suppressed and less sensitive. Experiments were designed to test the effect of controlled high and low dietary salt intake in patients with preeclampsia, healthy pregnant controls and non-pregnant controls. 24 h urine Na excretion, blood pressure, cardiac output – and extracellular volume (ECV) and plasma renin and aldosterone were measured. Secondary outcomes were pulsatile index (PI) in the umbilical artery and in the uterine artery. Methods The study (clintrialsgov NCT01828138) which is ongoing, is a randomized, cross-over, double-blinded, dietary intervention study (Ethic committee approval: 1-10-72-600-12). 7 patients with PE, 15 healthy pregnant women and 11 non pregnant women were included. The intervention was a fixed low-sodium diet (50–60 mmol/24 h) with addition of either placebo or salt tablets (200mmol) for 4 + 4 days. 24 h urine was collected for dietary compliance. After baseline measurements, outcome was measured after each of the two interventions. Results A significantly elevated systolic blood pressure (4 mmHg) was found in the healthy pregnant group ( P = 0.008) on a high salt diet. Plasma renin decreased significantly on a high salt diet in the healthy pregnant groups ( P = 0.02) and in non-pregnant group ( P P = 0.4). Comparing the delta values between groups, there was no difference. Plasma aldosterone decreased significantly on a high salt diet in all groups. Delta aldosterone was not different between groups. There was no statistically significant difference in cardiac output found in any of the groups. ECV increased significantly on a high salt diet in all groups. Umbilical artery PI was unaltered due to the intervention in both pregnant groups. PI in the uterine artery was significantly decreased in the group of preeclamptic women on a low salt diet ( P = 0.02) contrary to the healthy pregnant group ( P = 0.9). Conclusion There was a reduced reactivity of plasma renin concentration to altered salt intake in the pre-eclamptic group. Low salt intake was well-tolerated. PE/hypertension in pregnancy with proteinuria display features compatible with impaired sodium excretion that could involve ENaC activity.