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: Ravi Thadhani, Henning Hagmann, Wiebke Schaarschmidt, Bernhard Roth, Tuelay Cingoez, S Ananth Karumanchi, Julia Wenger, Kathryn J Lucchesi, Hector Tamez, Tom Lindner, Alexander Fridman, Ulrich Thome, Angela Kribs, Marco Danner, Stefanie Hamacher, Peter Mallmann, Holger Stepan, Thomas Benzing
• Journal: Journal of the American Society of Nephrology : JASN (J Am Soc Nephrol) Vol. 27 Issue 3 Pg. 903-13 (Mar 2016) ISSN: 1533-3450 [Electronic] United States
• PMID: 26405111 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2016 by the American Society of Nephrology.

Chemical References

• Dextran Sulfate
• FLT1 protein, human
• Vascular Endothelial Growth Factor Receptor-1

Topics

• Adult
• Birth Weight
• Blood Component Removal (adverse effects, methods)
• Blood Pressure
• Dextran Sulfate (chemistry, therapeutic use)
• Female
• Gestational Age
• Heart Rate, Fetal
• Humans
• Infant, Newborn
• Oxygen Inhalation Therapy
• Pilot Projects
• Pre-Eclampsia (blood, therapy)
• Pregnancy
• Pregnancy Maintenance
• Premature Birth (prevention & control)
• Proteinuria (therapy)
• Vascular Endothelial Growth Factor Receptor-1 (blood, chemistry)
• Young Adult