HUPP-study -Hypertension and Urine Protease Activity in Preeclampsia
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 35
- 试验地点
- 2
- 主要终点
- urine Plasmin/plasminogen correlation to the severity of preeclampsia
研究概览
简要总结
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:
- 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.
- The degree of aldosterone suppression in PE determines placental development
详细描述
Selection of patients:
The selection of patients is based on outpatients with preeclampsia and patients with normal pregnancies recruited from gynecological-obstetric department, Aarhus University Hospital - Skejby, Denmark. Non- pregnant woman are recruited by posting notices at the workplace. Specifically by office facilities, canteen and in gynecological department at Skejby hospital, Aarhus.
Background information:
Registration of date of birth, sex, weight, height, abdominal circumference, and smoking status will be noted.
Furthermore, we will register current antihypertensive-, diuretic-, antidiabetic- and antiepileptic medicine and other current use of medicine. Also post-partum registration of gestation length, placentas weight and the infant weight will be noted.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 45 Years（Adult）
- 性别
- Female
- 接受健康志愿者
- 是
入选标准
- •Pregnancy week 28-36 (exclusion of patients with previously severe preeclampsia).
- •Singleton pregnancy
- •Preeclampsia- hypertension: repetitive high blood pressures (> 140/80 mm Hg) measured in the consultation and proteinuria (dip test, albumin).
- •Pregnant with microalbuminuria and proteinuria, but without hypertension (and therefore do not meet the diagnostic criteria for preeclampsia) can also be included. Proteinuria is the most important factor.
- •It is still possible to test our hypothesis with possible comorbidity such as diabetes, SLE(systemic lupus erythematosus), rheumatoid arthritis and therefore not a reason for exclusion.
排除标准
- •Hypertension in pregnancy without proteinuria.
- •Pregestational nephropathy by other unknown reasons.
- •Early severe preeclampsia.
- •Organic or systemic disease of clinical relevance, such as malignancy.
- •Pregnant controls-
- •Inclusion Criteria:
- •pregnancy week 28-36
- •Singleton pregnancy
- •Uncomplicated pregnancy
- •Exclusion Criteria:
- •Hypertension
- •Any kind of nephropathy
- •Organic or systemic disease of clinical relevance, such as malignancy.
- •Non-pregnant controls:
- •Inclusion Criteria:
- •woman, not pregnant
- •Matched by age and BMI
- •Exclusion Criteria:
- •Hypertension
- •Any kind of nephropathy
- •Organic or systemic disease of clinical relevance, such as malignancy.
结局指标
主要结局
urine Plasmin/plasminogen correlation to the severity of preeclampsia
时间窗: 3 years
We suggest that the loss of plasmin/plasminogen are shared for the diseases with proteinuria, including PE, and that plasmin- driven ENaC activation is a causal factor in the pathophysiology of established PE. We believe that high concentrations of plasmin/plasminogen in the urine correlates to the severity og preeclampsia. -Another outcome measure is the correlation between plasma aldosterone and the placental (under)development.
次要结局
- correlation between RAAS components in urine and severity of preeclampsia(3 years)
- Degree of aldosterone suppression in PE determines placental development(3 years)
研究者
Lise Hald Nielsen
doctor, Ph.D student
Odense University Hospital