>"In a normal pregnancy, the developing fetus signals the mother's body to widen blood vessels to the placenta, which supplies oxygen and nutrients to the fetus," explains Karumanchi. "But for women with preeclampsia, the blood vessels grow narrower, which causes a host of life-threatening complications. Our discovery suggested this was happening because the anti-angiogenic protein sFlt1 [soluble fms-like tyrosine kinase 1] was attaching to and absorbing two pro-angiogenic proteins, PIGF [placental growth factor] and VEGF [vascular endothelial growth factor]." Last year, in a study published in The New England Journal of Medicine, Karumanchi and co-investigators confirmed that sFlt1 levels do indeed rise while PIGF levels fall approximately five weeks prior to the onset of preeclampsia symptoms in pregnant women.

The objective of this latest study, he explains, was to find out if these same proteins could be measured in urine, the thinking being that if this proved to be the case a simple urine test could provide a less invasive and less expensive screening tool to detect preeclampsia at an early stage.

Because the sFlt1 molecule is too large to be filtered through urine, the investigators focused on the PIGF molecule, testing the hypothesis that urinary PIGF levels would drop prior to the development of hypertension and proteinuria in pregnant women and could, therefore, predict which women would go on to develop preeclampsia.

Using archived urine specimens from the Calcium for Preeclampsia Prevention Trial (a large cohort study based at the National Institute of Child Health and Development), Karumanchi, in collaboration with Richard Levine, MD, MPH, of the NICHD, compared the PIGF levels of 118 women who had normal pregnancies with those of 120 women who went on to develop preeclampsia.

The results demonstrated that urinary PIGF levels were dramatically lower in the preeclamptic patients at both the time of clinical symptoms and
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Contact: Bonnie Prescott
bprescot@bidmc.harvard.edu
617-667-7306
Beth Israel Deaconess Medical Center
4-Jan-2005

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