title: Pilot study of extracorporeal removal of soluble fms-like tyrosine kinase 1 in preeclampsia.
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.
  
  
  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.
authors.affiliation: Division of Nephrology, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA. thadhani.r@mgh.harvard.edu
authors.forename: Ravi
authors.initials: R
authors.lastname: Thadhani
authors.forename: Tuelay
authors.initials: T
authors.lastname: Kisner
authors.forename: Henning
authors.initials: H
authors.lastname: Hagmann
authors.forename: Verena
authors.initials: V
authors.lastname: Bossung
authors.forename: Stefanie
authors.initials: S
authors.lastname: Noack
authors.forename: Wiebke
authors.initials: W
authors.lastname: Schaarschmidt
authors.forename: Alexander
authors.initials: A
authors.lastname: Jank
authors.forename: Angela
authors.initials: A
authors.lastname: Kribs
authors.forename: Oliver A
authors.initials: OA
authors.lastname: Cornely
authors.forename: Claudia
authors.initials: C
authors.lastname: Kreyssig
authors.forename: Linda
authors.initials: L
authors.lastname: Hemphill
authors.forename: Alan C
authors.initials: AC
authors.lastname: Rigby
authors.forename: Santosh
authors.initials: S
authors.lastname: Khedkar
authors.forename: Tom H
authors.initials: TH
authors.lastname: Lindner
authors.forename: Peter
authors.initials: P
authors.lastname: Mallmann
authors.forename: Holger
authors.initials: H
authors.lastname: Stepan
authors.forename: S Ananth
authors.initials: SA
authors.lastname: Karumanchi
authors.forename: Thomas
authors.initials: T
authors.lastname: Benzing
mesh_terms: D000328:Adult; D001781:Blood Component Removal / Q000379:methods*; D002482:Cellulose / Q000737:chemistry; D016264:Dextran Sulfate / Q000737:chemistry; D005260:Female; D006801:Humans; D010865:Pilot Projects; D011225:Pre-Eclampsia / Q000097:blood* / Q000628:therapy*; D011247:Pregnancy; D017434:Protein Structure, Tertiary; D012995:Solubility; D016896:Treatment Outcome; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000097:blood* / Q000737:chemistry / Q000302:isolation & purification; D055815:Young Adult
chemical_list: D002482:Cellulose; D016264:Dextran Sulfate; C501162:FLT1 protein, human; D040281:Vascular Endothelial Growth Factor Receptor-1