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.
Phase:
N/A
Details
Lead Sponsor:
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)