The Promise of Angiogenic Markers for the Early Diagnosis and Prediction of Preeclampsia
ABSTRACT An imbalance in circulating factors that regulate blood vessel formation and health, referred to as angiogenic factors, plays a central role in the pathogenesis of preeclampsia.
Several studies have demonstrated a strong association between altered circulating angiogenic factors and preeclampsia. These factors include circulating antiangiogenic proteins such as soluble fms-like tyrosine kinase 1 and soluble endoglin and proangiogenic protein such as placental growth factor. Abnormalities in these circulating angiogenic factors are not only present during clinical disease, but also antedate clinical signs and symptoms by several weeks. These alterations are particularly prominent in patients who present with preeclamptic signs and symptoms prematurely and/or in patients with severe preeclampsia. The availability of automated platforms for the rapid measurement of circulating angiogenic proteins in blood samples has now allowed researchers and clinicians to evaluate the utility of these assays in the diagnosis of the disease, in the stratification of patients in clinical trials, or in the monitoring of therapies. In this review we highlight the various studies that have been performed, with a focus on large validation studies.
Measurement of circulating angiogenic proteins for the diagnosis and prediction of preeclampsia is still at an early stage but is rapidly evolving. Standardization across the various automated platforms and prospective studies that demonstrate clinical utility are needed.
Article: Pathogenesis of preeclampsia.[Show abstract] [Hide abstract]
ABSTRACT: Preeclampsia is a gestational kidney disease characterized by glomerular endothelial injury, leading to maternal hypertension and proteinuria. If not addressed promptly, there is significant maternal and fetal morbidity and mortality. When severe, this disorder can cause hepatic and neurologic dysfunction. Understandably, this placental disease enters the focus of the obstetrician first; however, with progression, the nephrologist can also be enlisted. Typical complications include acute kidney injury, refractory hypertension, and acute pulmonary edema. This review summarizes recent literature on the pathogenesis of this condition and will highlight new diagnostic and therapeutic options for preeclampsia. Over the past decade, the role of soluble vascular factors in preeclampsia has shed light on the mechanism underlying this disease. During the last 2 years, several new therapeutics have been developed that target implicated circulating angiogenic factors, including soluble fms-like tyrosine kinase 1, an endogenous vascular endothelial growth factor inhibitor. Serum levels of angiogenic factors have been correlated with a constellation of hemodynamic and pathophysiologic changes. Thus, circulating levels of these factors may serve both diagnostic and prognostic purposes. Overall, our understanding of preeclampsia has developed significantly and the future holds promise for mechanism-based novel diagnostics and therapeutics.
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ABSTRACT: To assess how routine clinical use of the Roche fully automated Elecsys® sFlt-1/PlGF test changes decision-making of physicians to hospitalize pregnant women with suspected preeclampsia. The Preeclampsia Open Study (PreOS) study is a multicenter, prospective, open-label, non-interventional study in 150 women showing signs and symptoms of preeclampsia (suspected preeclampsia). Physicians record their intended procedures before and after knowledge of participants' sFlt-1/PlGF ratio. The study is conducted at five investigational sites in Germany and Austria. The PreOS study will provide evidence on how sFlt-1/PlGF ratio testing influences clinical decision-making in women with suspected preeclampsia in real-world clinical practice.
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ABSTRACT: Background: Higher 1 st trimester maternal serum levels of interferon-induced protein 10 (IP-10) and interferon inducible T-cell alpha chemoattractant (ITAC) are reported in gestations complicated with preeclampsia. However, parallel results in the fetal circulation are lacking. Objective: To compare IP-10 and ITAC levels in neonatal cord blood from gestations complicated by severe preeclampsia vs. gestational age-matched controls. Method: Umbilical cord vessels were sampled following delivery of women with severe preeclampsia (n = 30) ≥ 36 weeks to measure plasma IP-10 and ITAC levels and compared to corresponding controls matched for parity as well as maternal and gestational age. Chemokines were measured by specific ELISAs and expressed as pg/mL. Rho Spearman ’ s coefficients were calculated to establish correlations between chemokine values and various numeric variables. Results: Preeclamptic cases displayed significantly lower median plasma umbilical artery and vein levels of both chemokines when compared to controls (IP-10: 23.4 vs. 31.4 and 2.0 vs. 24.6 pg/mL, P < 0.05; and ITAC: 2.0 vs. 13.9 and 11.9 vs. 31.6 pg/mL, P < 0.05, in artery and vein, respectively). There was a significant correlation between levels of both chemokines (r 2 = 0.616, P = 0.0001), but not with other variables. Conclusion: In contrast to elevated 1 st trimester levels of IP-10 previously found in the maternal serum of women who later developed preeclampsia, this study found lower umbilical cord IP-10 and ITAC plasma levels in near-term gestations with established severe preeclampsia.Journal of Perinatal Medicine 05/2015; DOI:10.1515/jpm-2014-0371 · 1.43 Impact Factor