title: Removal of Soluble Fms-Like Tyrosine Kinase-1 by Dextran Sulfate Apheresis in Preeclampsia.
abstract: Preeclampsia is a devastating complication of pregnancy. Soluble Fms-like tyrosine kinase-1 (sFlt-1) is an antiangiogenic protein believed to mediate the signs and symptoms of preeclampsia. We conducted an open pilot study to evaluate the safety and potential efficacy of therapeutic apheresis with a plasma-specific dextran sulfate column to remove circulating sFlt-1 in 11 pregnant women (20-38 years of age) with very preterm preeclampsia (23-32 weeks of gestation, systolic BP ≥140 mmHg or diastolic BP ≥90 mmHg, new onset protein/creatinine ratio >0.30 g/g, and sFlt-1/placental growth factor ratio >85). We evaluated the extent of sFlt-1 removal, proteinuria reduction, pregnancy continuation, and neonatal and fetal safety of apheresis after one (n=6), two (n=4), or three (n=1) apheresis treatments. Mean sFlt-1 levels were reduced by 18% (range 7%-28%) with concomitant reductions of 44% in protein/creatinine ratios. Pregnancy continued for 8 days (range 2-11) and 15 days (range 11-21) in women treated once and multiple times, respectively, compared with 3 days (range 0-14) in untreated contemporaneous preeclampsia controls (n=22). Transient maternal BP reduction during apheresis was managed by withholding pre-apheresis antihypertensive therapy, saline prehydration, and reducing blood flow through the apheresis column. Compared with infants born prematurely to untreated women with and without preeclampsia (n=22 per group), no adverse effects of apheresis were observed. In conclusion, therapeutic apheresis reduced circulating sFlt-1 and proteinuria in women with very preterm preeclampsia and appeared to prolong pregnancy without major adverse maternal or fetal consequences. A controlled trial is warranted to confirm these findings.
authors.affiliation: Division of Nephrology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts; rthadhani@mgh.harvard.edu.
authors.forename: Ravi
authors.initials: R
authors.lastname: Thadhani
authors.affiliation: Renal Division and Department of Medicine and Center for Molecular Medicine.
authors.forename: Henning
authors.initials: H
authors.lastname: Hagmann
authors.affiliation: Department of Obstetrics.
authors.forename: Wiebke
authors.initials: W
authors.lastname: Schaarschmidt
authors.affiliation: Department of Neonatology.
authors.forename: Bernhard
authors.initials: B
authors.lastname: Roth
authors.affiliation: Renal Division and Department of Medicine and Center for Molecular Medicine.
authors.forename: Tuelay
authors.initials: T
authors.lastname: Cingoez
authors.affiliation: Department of Medicine and Obstetrics and Gynecology, and Howard Hughes Medical Institute, Chevy Chase, Maryland.
authors.forename: S Ananth
authors.initials: SA
authors.lastname: Karumanchi
authors.affiliation: Division of Nephrology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts;
authors.forename: Julia
authors.initials: J
authors.lastname: Wenger
authors.affiliation: Division of Nephrology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts;
authors.forename: Kathryn J
authors.initials: KJ
authors.lastname: Lucchesi
authors.affiliation: Department of Cardiology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts; and.
authors.forename: Hector
authors.initials: H
authors.lastname: Tamez
authors.affiliation: Division of Nephrology, Department of Internal Medicine, Neurology, and Dermatology, and.
authors.forename: Tom
authors.initials: T
authors.lastname: Lindner
authors.affiliation: Department of Obstetrics and Gynecology.
authors.forename: Alexander
authors.initials: A
authors.lastname: Fridman
authors.affiliation: Department of Neonatology, University Hospital Leipzig, Leipzig, Germany;
authors.forename: Ulrich
authors.initials: U
authors.lastname: Thome
authors.affiliation: Department of Neonatology.
authors.forename: Angela
authors.initials: A
authors.lastname: Kribs
authors.affiliation: Department of Neonatology.
authors.forename: Marco
authors.initials: M
authors.lastname: Danner
authors.affiliation: Institute of Medical Statistics, Informatics and Epidemiology, and.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Hamacher
authors.affiliation: Department of Obstetrics and Gynecology.
authors.forename: Peter
authors.initials: P
authors.lastname: Mallmann
authors.affiliation: Department of Obstetrics.
authors.forename: Holger
authors.initials: H
authors.lastname: Stepan
authors.affiliation: Renal Division and Department of Medicine and Center for Molecular Medicine, Cologne Excellence Cluster on Cellular Stress Response in Aging Associated Diseases, University of Cologne, Cologne, Germany;
authors.forename: Thomas
authors.initials: T
authors.lastname: Benzing
mesh_terms: D000328:Adult; D001724:Birth Weight; D001781:Blood Component Removal / Q000009:adverse effects / Q000379:methods*; D001794:Blood Pressure; D016264:Dextran Sulfate / Q000737:chemistry / Q000627:therapeutic use*; D005260:Female; D005865:Gestational Age; D006340:Heart Rate, Fetal; D006801:Humans; D007231:Infant, Newborn; D010102:Oxygen Inhalation Therapy; D010865:Pilot Projects; D011225:Pre-Eclampsia / Q000097:blood / Q000628:therapy*; D011247:Pregnancy; D011255:Pregnancy Maintenance; D047928:Premature Birth / Q000517:prevention & control; D011507:Proteinuria / Q000628:therapy; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000097:blood* / Q000737:chemistry; D055815:Young Adult
chemical_list: D016264:Dextran Sulfate; C501162:FLT1 protein, human; D040281:Vascular Endothelial Growth Factor Receptor-1
keywords: clinical trial; preeclampsia; pregnancy; sFlt-1; therapeutic apheresis; vascular endothelial growth factor