Pilot Study of Extracorporeal Removal of Soluble Fms-Like Tyrosine Kinase 1 in Preeclampsia

被引:259
作者
Thadhani, Ravi [1 ]
Kisner, Tuelay [2 ,3 ,4 ]
Hagmann, Henning [2 ,3 ,4 ]
Bossung, Verena [5 ]
Noack, Stefanie
Schaarschmidt, Wiebke [9 ]
Jank, Alexander [9 ]
Kribs, Angela [6 ]
Cornely, Oliver A. [7 ,8 ]
Kreyssig, Claudia [10 ]
Hemphill, Linda [1 ]
Rigby, Alan C. [11 ]
Khedkar, Santosh [11 ]
Lindner, Tom H. [10 ]
Mallmann, Peter [5 ]
Stepan, Holger [9 ]
Karumanchi, S. Ananth [11 ,12 ]
Benzing, Thomas [2 ,3 ,4 ]
机构
[1] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Nephrol,Dept Med, Boston, MA USA
[2] Univ Cologne, Div Renal, Cologne, Germany
[3] Univ Cologne, Dept Med, Cologne, Germany
[4] Univ Cologne, Ctr Mol Med, Cologne, Germany
[5] Univ Cologne, Dept Obstet & Gynecol, Cologne, Germany
[6] Univ Cologne, Dept Neonatol, Cologne, Germany
[7] Univ Cologne, Dept Internal Med, Cologne, Germany
[8] Univ Cologne, Clin Trials Ctr, ZKS Koln, Cologne, Germany
[9] Univ Hosp Leipzig, Dept Obstet, Leipzig, Germany
[10] Univ Hosp Leipzig, Div Nephrol, Dept Internal Med Neurol & Dermatol, Leipzig, Germany
[11] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Med, Boston, MA 02215 USA
[12] Howard Hughes Med Inst, Chevy Chase, MD USA
关键词
angiogenic factor; apheresis; preeclampsia; GROWTH-FACTOR RECEPTOR-1; HOMOZYGOUS FAMILIAL HYPERCHOLESTEROLEMIA; DENSITY-LIPOPROTEIN APHERESIS; EXPECTANT MANAGEMENT; CITRATE ANTICOAGULATION; VEGF RECEPTOR-1; HEPARIN-BINDING; WEEKS GESTATION; HYPERTENSION; PREGNANCY;
D O I
10.1161/CIRCULATIONAHA.111.034793
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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. (Circulation. 2011;124:940-950.)
引用
收藏
页码:940 / U178
页数:18
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