Selections from the 25th Annual Meeting of the Society for Maternal-Fetal Medicine, February 9-12, Reno, Nevada
Urinary angiogenic factors cluster hypertensive disorders and identify women with severe preeclampsia

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Objective

Serum levels of soluble fms-like tyrosine kinase 1 (sFlt-1), vascular endothelial growth factor (VEGF), and placental growth factor (PlGF) are altered in women with clinical preeclampsia. We sought to identify whether similar alterations in urinary levels of these proteins cluster hypertensive disorders in pregnancy, and identify women with severe preeclampsia (sPE).

Study design

Free urinary levels of sFlt-1, VEGF, and PlGF were measured by immunoassay in 68 women enrolled prospectively in the following groups: nonpregnant reproductive age (NP-CTR n = 14), healthy pregnant control (P-CTR n = 16), pregnant hypertensive and proteinuric women who did not meet criteria for severe preeclampsia (pHTN n = 21), and women with sPE (n = 17).

Results

There was no difference in gestational age at the time of enrollment among groups (median [range]: sPE: 31 [24-40], pHTN: 34 [16-40], P-CTR: 28 [7-39] wks). Urinary excretion of VEGF was significantly increased in sPE women compared with NP-CTR (P = .023), but did not differ among pregnant groups. Urinary PlGF levels were significantly increased in pregnant compared with nonpregnant women, but were decreased in all hypertensive women compared with healthy P-CTR (P < .001). Urinary sFlt-1 concentrations were significantly increased in women with sPE relative to all other groups (P < .001). pHTN women had higher sFlt-1 urinary output compared with P-CTR group (P = .001). A cutoff >2.1 in the ratio log [sFlt-1/PlGF] had 88.2% sensitivity and 100% specificity in differentiating women with sPE from normotensive controls. We also described that the log[sFlt-1/PlGF] ratio identified women with sPE better than proteinuria alone (P = .03). Our regression model revealed that uric acid correlated best with log[sFlt-1/PlGF] ratio (r = 0.628; P = .005).

Conclusion

sPE is associated with increased urinary output of the antiangiogenic factor sFlt-1 and a decreased output of PlGF at the time of clinical manifestation, providing a rapid noninvasive screening of hypertensive women based on a sFlt/PlGF ratio. This ratio may be used as representation for severity of the disease, and appears to be superior to random urinary protein measurements.

Section snippets

Participants and sample collection

We studied samples of urine from 68 women admitted at Yale New Haven Hospital between February and August 2004. Samples were collected under protocols approved by the Human Investigation Committee of Yale University. Written informed consent was obtained from all participants. Gestational age was established based on menstrual date and/or ultrasonographic examination before 20 weeks' gestation. All women solicited for enrollment in the study agreed to participate. We requested enrollment from

Characteristics of women

Out of 68 patients enrolled in this study, 17 met criteria for sPE. By study design, our patients were enrolled prospectively, so that at the time of enrollment we were aware only whether a subject is or is not hypertensive and proteinuric, and whether it meets or does not meet the clinical criteria for sPE. Because at the time of enrollment we could not precisely establish the nature of the hypertensive condition, the pHTN group (n = 21) was heterogeneous, consisting of women with mild

Comment

We found that urinary sFlt-1 and PlGF are altered in women with hypertensive disorders during pregnancy. We further observed that a ratio between the two functionally opposing angiogenic factors, sFlt-1 and PlGF, has high sensitivity and specificity in differentiating women with sPE from normotensive controls. Most importantly, we discovered that the ratios between sFlt-1 and PlGF could discriminate sPE from other forms of proteinuric hypertensive disorders, including mild preeclampsia with or

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    Oral presentation at the 25th Annual Meeting of the Society for Maternal-Fetal Medicine, February 7-12, 2005, Reno, Nev.

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