Hypertension and Urine Protease Activity in Preeclampsia

Summary

Preeclampsia (PE) is a common disorder of pregnancy that complicates 4-7% of all pregnancies. It is a serious condition with acute proteinuria and hypertension and varying degrees of edema after 20 weeks of gestation. PE leads to a severe risk of low birth weight because of prematurity with inherent complications. The pathogenesis is unknown but is assumed to involve placental ischemia.The primary placental disorder results in renal glomerular injury. Established PE is associated with paradoxical suppression of the renin-angiotensin-aldosterone system, RAAS.

Despite suppressed RAAS, patients with PE retain NaCl(sodium chloride) after an intravenous isotonic NaCl overload compared to healthy pregnant women on a low NaCl diet. The investigators believe to have data that provide a possible explanation for the overall relationship between proteinuria, NaCl retension, suppression of RAAS, hypertension and underdevelopment of placenta. Earlier data, which the investigators have confirmed, shows abnormal glomerular loss of the enzyme plasmin/plasminogen from plasma to the urine in PE. Active plasmin in urine from patients with nephrotic syndrome and PE activates the epithelial sodium channel ( ENaC ) in renal collecting duct cells. The investigators hypothesize that loss of plasmin/plasminogen are shared for the diseases with proteinuria, including PE, and that plasmin- driven ENaC (epithelial sodium channel) activation is a causal factor in the pathophysiology of established PE. Hyperactive ENaC causes primary renal sodium retention with secondary suppression of the renin-angiotensin-aldosterone system. Aldosterone is recently established as a placental growth factor.

Plasma-aldosterone levels are significant higher in normal pregnant women. PE is characterized by low aldosterone levels (a discovery the investigators have also confirmed) and by placental underdevelopment.

Study Aim: To test specific hypothesis regarding established PE´s pathophysiological mechanisms.

Study Hypothesis:

1. Excretion of urine proteases (plasmin/plasminogen) in PE leads to an activation of ENaC and hence RAAS is less NaCl sensitive while the blood pressure is more NaCl sensitive compared to healthy pregnant women.
2. The degree of aldosterone suppression in PE determines placental development

Conditions

• Preeclampsia
• Hypertension
• Proteinuria
• Pregnancy

Interventions

DIETARY_SUPPLEMENT

Sodium

supplemental sodium tablets 150-200 mmol/day in 5 days

DIETARY_SUPPLEMENT

Placebo

Placebo are given in 5 days

Sponsors & Collaborators

• The Danish Council for Strategic Research

  collaborator OTHER

• Lundbeck Foundation

  collaborator OTHER

• Odense University Hospital

  lead OTHER

Principal Investigators

• Boye L. Jensen, Professor · cardiovascular and renal research department, Odense University Hospital

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Model

CROSSOVER

Eligibility

Min Age

18 Years

Max Age

45 Years

Sex

FEMALE

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2013-05-31

Primary Completion

2015-10-31

Completion

2015-10-31

Countries

• Denmark

Study Locations