Glomerular Injury of Preeclampsia

This study has been completed.
Sponsor:
Collaborator:
Information provided by:
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
ClinicalTrials.gov Identifier:
NCT00275158
First received: January 10, 2006
Last updated: January 12, 2010
Last verified: January 2010
  Purpose

Pre-eclampsia complicates 7 - 10% of pregnancies and constitutes a leading cause of fetal growth retardation and premature birth, as well as infant and maternal morbidity and mortality. The kidney is the primary site of injury resulting in high blood pressure, loss of protein into the urine and decreased kidney function. The release of vasoconstrictors over vasodilators from an abnormal placenta may underlie pre-eclampsia. Nitric Oxide (NO) is an important vasodilator that is thought to play an important role in the kidneys ability to accommodate to a healthy pregnancy. Normal pregnancy in the rat is accompanied by increased production of NO and its second messenger cGMP. There is a parallel increase in renal expression of constitutive nitric oxide synthase (NOS), the enzyme that generates NO from arginine. In the pregnant rat, an infusion of NG-nitro-L-arginine methyl ester (L-NAME), an exogenous inhibitor of NOS, has been shown to replicate some of the hemodynamic features of the syndrome of pre-eclampsia. In a recent animal study, L-arginine supplementation reversed the adverse effects of L-NAME on pregnancy by attenuating the high blood pressure and by significantly decreasing protein loss in the urine. To date, studies of the use of L-arginine supplementation to treat women with pre-eclampsia have been small or uncontrolled and have only assessed blood pressure as a primary outcome measure. We report a single center, randomized, placebo-controlled trial of L-arginine supplementation for the treatment of pre-eclampsia, in which precise physiological techniques have been utilized to assess kidney dysfunction in addition to blood pressure.


Condition Intervention
Pre-Eclampsia
Drug: L-Arginine Supplementation

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double-Blind
Primary Purpose: Treatment
Official Title: Effect of L-Arginine Therapy on the Glomerular Injury of Pre-Eclampsia: A Randomized Controlled Trial

Resource links provided by NLM:


Further study details as provided by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK):

Primary Outcome Measures:
  • Mean Arterial Pressure [ Designated as safety issue: No ]
  • Glomerular Filtration Rate (inulin clearance)
  • Proteinuria (albumin to creatinine ratio)

Secondary Outcome Measures:
  • Vasoactive hormone levels - Nitric Oxide, Endothelin, cGMP, ADMA
  • Neonatal Outcomes

Estimated Enrollment: 45
Study Start Date: January 2000
Study Completion Date: December 2003
Detailed Description:

OBJECTIVE: To assess the benefit of L-arginine, the precursor to nitric oxide (NO), to blood pressure and recovery of the glomerular lesion in pre-eclampsia.

METHODS: 45 women with pre-eclampsia were randomized to receive either L-arginine or placebo until day 10 post-partum. Primary outcome measures including MAP, glomerular filtration rate and proteinuria were assessed on the third and tenth days postpartum by inulin clearance and albumin-to-creatinine (A/C) ratio. NO, cyclic guanosine 3'5' monophosphate (cGMP), endothelin-1 (ET) and asymmetric-dimethyl-arginine (ADMA) and arginine levels were assayed prior to delivery, on the third and tenth day postpartum. Healthy gravid women provided control values. Assuming a standard deviation of 10 mmHg, the study was powered to detect a 10 mmHg difference in MAP (alpha 0.05, beta 0.20) between the study groups.

RESULTS: No significant differences existed between the groups with pre-eclampsia prior to randomization. Compared to the gravid control group, women with pre-eclampsia did not reveal significantly depressed levels of serum arginine, but did reveal significantly increased serum levels of ET, cGMP and ADMA prior to delivery. Despite a significant increase in serum arginine levels due to treatment, no differences were found in the levels of NO, ET, cGMP or ADMA between the two groups with pre-eclampsia. Further, there were no significant differences in any of the primary outcome measures with both groups demonstrating equivalent improvements in both blood pressure and proteinuria.

CONCLUSION: Blood pressure and kidney function improve markedly in pre-eclampsia by the tenth day postpartum. L-arginine supplementation does not hasten this recovery.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

- Women selected for the study were diagnosed with pre-eclampsia in the second half of pregnancy.

i.) an elevation of blood pressure to levels in excess of 140 systolic over 90 diastolic ii.) proteinuria determined by a urine dipstick value ≥ 2+, or quantitated at ≥ 0.5 g either per gram of creatinine or in a 24 hour urine collection.

Exclusion Criteria:

  • Women with a history of underlying renal disease defined as a pre-pregnancy azotemia (serum creatinine ≥ 1.2 mg/dl) or proteinuria
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00275158

Locations
United States, California
Stanford University Medical Center
Stanford, California, United States, 94305
Sponsors and Collaborators
Investigators
Principal Investigator: Bryan D Myers, MD Stanford University
  More Information

No publications provided

Responsible Party: Bryan Myers, Stanford University
ClinicalTrials.gov Identifier: NCT00275158     History of Changes
Other Study ID Numbers: DK-52876 (completed), DK-52876
Study First Received: January 10, 2006
Last Updated: January 12, 2010
Health Authority: United States: Federal Government

Keywords provided by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK):
Pre-Eclampsia
Glomerular Filtration Rate (GFR)
Inulin clearance
Hypertension
L-Arginine
Nitric Oxide
cGMP
Endothelin
ADMA

Additional relevant MeSH terms:
Eclampsia
Pre-Eclampsia
Wounds and Injuries
Hypertension, Pregnancy-Induced
Pregnancy Complications

ClinicalTrials.gov processed this record on July 22, 2014