Pre-Eclampsia & HELLP!

The pre-eclampsia story (which I have mentioned previously on this blog) is one of the triumphs of basic nephrology research over the past few years, and apparently the folks at the ASN thought so as well, as Dr. S. Ananth Karumanchi received the Young Investigator Award this year.  He gave a very nice overview of this story at his talk.  To summarize:  most women with pre-eclampsia have high levels of sFlt-1, a VEGF receptor antagonist elaborated by the placenta.  When transferred to pregnant rats, purified sFlt-1 recapitulates the thrombotic microangiopathy phenotype, proving that sFlt-1 is not only correlative but also causative.  Intriguingly, Dr. Karumanchi presented data showing that routine blood samples from pregnant women several weeks PRIOR to their diagnosis of pre-eclampsia showed elevated sFlt-1 levels.  This suggests that an assay for sFlt-1 could well be used for early identification of women who will go on to develop pre-eclampsia.  

One missing piece to the puzzle, however, was that sFlt-1 injection in rats did not seem to produce any liver pathology.  How does one explain the existence of the related HELLP Syndrome (HELLP = hemolysis, elevated liver enzymes, and low platelets) with this supposedly unifying theory for pre-eclampsia?  It turns out that another circulating protein produced by the placenta--soluble endoglin--may be responsible for this.  Circulating endoglin levels are higher in individuals withi HELLP, and co-njection of both sFlt-1 + soluble endoglin into animals leads to both endothelial and liver damage.