Pilot study of extracorporeal removal of soluble Fms-like tyrosine kinase 1 in preeclampsia

Ravi Thadhani*, Tuelay Kisner, Henning Hagmann, Verena Bossung, Stefanie Noack, Wiebke Schaarschmidt, Alexander Jank, Angela Kribs, Oliver A. Cornely, Claudia Kreyssig, Linda Hemphill, Alan C. Rigby, Santosh Khedkar, Tom H. Lindner, Peter Mallmann, Holger Stepan, S. Ananth Karumanchi, Thomas Benzing

*Korrespondierende/r Autor/-in für diese Arbeit
238 Zitate (Scopus)

Abstract

Background-: Targeted therapies to stabilize the clinical manifestations and prolong pregnancy in preeclampsia do not exist. Soluble fms-like tyrosine kinase 1 (sFlt-1), an alternatively spliced variant of the vascular endothelial growth factor receptor 1, induces a preeclampsia-like phenotype in experimental models and circulates at elevated levels in human preeclampsia. Removing sFlt-1 may benefit women with very preterm (<32 weeks) preeclampsia. Methods and results-: We first show that negatively charged dextran sulfate cellulose columns adsorb sFlt-1 in vitro. In 5 women with very preterm preeclampsia and elevated circulating sFlt-1 levels, we next demonstrate that a single dextran sulfate cellulose apheresis treatment reduces circulating sFlt-1 levels in a dose-dependent fashion. Finally, we performed multiple apheresis treatments in 3 additional women with very preterm (gestational age at admission 28, 30, and 27+4 weeks) preeclampsia and elevated circulating sFlt-1 levels. Dextran sulfate apheresis lowered circulating sFlt-1, reduced proteinuria, and stabilized blood pressure without apparent adverse events to mother and fetus. Pregnancy lasted for 15 and 19 days in women treated twice and 23 days in a woman treated 4 times. In each, there was evidence of fetal growth. Conclusions-: This pilot study supports the hypothesis that extracorporeal apheresis can lower circulating sFlt-1 in very preterm preeclampsia. Further studies are warranted to determine whether this intervention safely and effectively prolongs pregnancy and improves maternal and fetal outcomes in this setting.

OriginalspracheEnglisch
ZeitschriftCirculation
Jahrgang124
Ausgabenummer8
Seiten (von - bis)940-950
Seitenumfang11
ISSN0009-7322
DOIs
PublikationsstatusVeröffentlicht - 23.08.2011

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