TY - JOUR
T1 - Pilot study of extracorporeal removal of soluble Fms-like tyrosine kinase 1 in preeclampsia
AU - Thadhani, Ravi
AU - Kisner, Tuelay
AU - Hagmann, Henning
AU - Bossung, Verena
AU - Noack, Stefanie
AU - Schaarschmidt, Wiebke
AU - Jank, Alexander
AU - Kribs, Angela
AU - Cornely, Oliver A.
AU - Kreyssig, Claudia
AU - Hemphill, Linda
AU - Rigby, Alan C.
AU - Khedkar, Santosh
AU - Lindner, Tom H.
AU - Mallmann, Peter
AU - Stepan, Holger
AU - Karumanchi, S. Ananth
AU - Benzing, Thomas
PY - 2011/8/23
Y1 - 2011/8/23
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=80052149662&partnerID=8YFLogxK
U2 - 10.1161/CIRCULATIONAHA.111.034793
DO - 10.1161/CIRCULATIONAHA.111.034793
M3 - Journal articles
C2 - 21810665
AN - SCOPUS:80052149662
SN - 0009-7322
VL - 124
SP - 940
EP - 950
JO - Circulation
JF - Circulation
IS - 8
ER -