Antiangiogenic Protein Under Study As Promising Preeclampsia Marker


CHICAGO — Measures of soluble fms-like tyrosine kinase 1 (sFlt-1), a circulating antiangiogenic protein secreted in excess by the placentas of women with preeclampsia, may prove to be a screening test for preeclampsia.

“Looking to the future, I have a lot of faith in blocking sFlt-1” as a possible treatment for preeclampsia, Dr. Sharon Maynard said in an interview after her presentation at a meeting on clinical nephrology sponsored by the National Kidney Foundation. The first phase I trial of an agent that blocks sFlt-1 will begin next year. If shown to be safe and effective, a potential treatment could be available within 3–4 years.

The ability to prevent and treat preeclampsia has long eluded medicine, said Dr. Maynard, a nephrologist at George Washington University. Most studies have addressed preventive therapies for preeclampsia: calcium, antioxidants, aspirin, magnesium, and blood pressure control.

Several small studies initially suggested that calcium supplementation could help prevent preeclampsia, but the findings did not hold up in later studies. Outcomes were comparable in one large trial that randomized more than 4,500 healthy nulliparous women to calcium or placebo (N. Engl. J. Med.1997;337:69–76). A subgroup analysis of these data indicated women with low baseline calcium levels may derive some benefit from supplements. A World Health Organization-sponsored trial of 5,000 women with low baseline calcium levels also revealed a lower risk of preeclampsia and neonatal death.

Antioxidants similarly failed to hold up to the rigors of a controlled trial in 2,395 women. In fact, the gravid women taking antioxidant supplements had a greater risk of low-birth-weight babies and stillbirths.

The data on aspirin in this population are “the most confusing of all,” noted Dr. Maynard. Although three large randomized controlled trials of 12,000 high-risk women found no differences with aspirin versus placebo, results were mixed in a subsequent metaanalysis of 51 trials involving 36,500 women. A Cochrane analysis showed that benefits were seen in small studies, but not in large ones. “I am really concerned that there may be no benefit at all,” she said.

Although magnesium has not been shown to prevent preeclampsia, it should be used “across the board. [It] clearly cuts the risk of seizures in half,” said Dr. Maynard.

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