Friday, November 14, 2008

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.  


CJ said...

Wow, Nathan, I am very impressed by your blog. I stumbled across it looking for review questions for the boards next week. If I had spent as much time every day during fellowship to read as you must to publish this blog, I would be less anxious about the boards right now. I read several months worth of entries and the short blurbs are great for review.

nathanhellman said...

Great to get your comment!

I'm currently a 2nd year fellow and therefore mostly doing lab research now--this blog is one way for me to keep in touch with clinical nephrology and hopefully will help me with the nephrology boards for next year--good luck!