#AskASN on Controversies in Nephrology: Pre-eclampsia and sFLT-1

This week, #NephJC will be handed over to #AskASN as we discuss pre-eclampsia and sFLT-1. Please join us Tuesday, May 30 at 9 PM EDT for the chat.

For this week’s #AskASN chat we are lucky to have three experts in pre-eclampsia joining us: Dr. Karumanchi is a nephrologist and Professor of Medicine at Harvard Medical School and Beth Israel Deaconess Medical Center. Dr. Tangren is a nephrology fellow at Massachusetts General Hospital and we discussed her article on pregnancy outcomes after AKI during a recent #NephJC chat. Finally, we have Dr. Rana, who is section chief of maternal-fetal medicine at the University of Chicago who is also joining us!

Pre-eclampsia has been described as the most common glomerular disease in the world. It complicates 5% of all pregnancies. The risk of preeclampsia in women with CKD, dialysis, and prior transplant is significantly higher than the general population. In addition, pre-eclampsia increases the risk of ESRD, making it both an important topic of conversation with our female patients from a counseling standpoint as well as an important piece of history to obtain when assessing the underlying cause of CKD.

Currently pre-eclampsia is diagnosed based upon clinical guidelines from the American College of Obstetricians and Gynecologists as shown in their table below:

It can be difficult to make the diagnosis of pre-eclampsia in women with CKD or atypical presentations. I once heard a talk on pre-eclampsia where the speaker estimated we only get the diagnosis right 50% of the time in patients with CKD. Fortunately, our understanding of the pathogenesis of pre-eclampsia has come a long way since then and has led to sFLT-1 as a potential biomarker as well as a potential treatment target.

During pregnancy, normal development of the placenta requires extensive angiogenesis. To achieve this, the placenta produces a balance of proangiogenic (VEGF, PlGF) and antiangiogenic factors (sFlt-1). sFLT-1 antagonizes circulating VEGF and PIGF and prevents their interaction with endogenous receptors and is found in significantly higher concentrations in women with clinical pre-eclampsia as well as in women who ultimately developed pre-eclampsia. PIGF levels are also significantly lower in the same population.

The recognition of the role of sFLT-1 in pre-eclampsia has led to the proposal of using the ratio of sFLT-1:PIGF to aid in diagnosis. Indeed, PROGNOSIS (Prediction of Short-Term Outcome in Pregnant Women with Suspected Preeclampsia Study) was able to determine a ratio level of 38 or less that had a negative predictive value of 99.3%! That is, in women in whom there was a clinical suspicion of pre-eclampsia, if they had a ratio of 38 or less, it was able to predict the absence of the development of pre-eclampsia over the next week extremely well. While these results are exciting, more research is needed prior to this ratio being used routinely in clinical practice, as succinctly pointed out in the editorial written by Dr. Seely and Dr. Solomon.

sFLT-1 is also being assessed as a potential therapeutic target in pre-eclampsia. The cure for pre-eclampsia remains delivery of the infant. This is not always the best option for the fetus: significant prematurity carries with it a high risk for death and disability of the infant. This has led to attempts to prolong the pregnancy by removing sFLT-1 using a dextran sulfate cellulose column. There have been two pilot studies published by the same group utilizing this technique. The first pilot was published in Circulation in 2011 and the second pilot study was published in JASN in 2015. Between the 2 pilot studies, a total of 19 women were treated with the apheresis technique one or more times leading to a reduction in circulating sFLT-1 and proteinuria without significant adverse effects to mom or child. Will this be a future treatment in severe preterm pre-eclampsia? Time will certainly tell! A search on ClinicalTrials.gov revealed that there is at least one trial, SAVE,  currently recruiting to assess the use of a sFlt-1 antibody adsorption column in pre-eclampsia.

I hope you’ll join us this Tuesday, May 30 at 9:00 pm EDT to talk more about the exciting advances being made in this field! It is sure to be a stimulating discussion! Also, don't forget: hashtag is #askASN, not #nephJC!

Suggested Reading

1.   Predictive Value of the sFlt-1:PlGF Ratio in Women with Suspected Preeclampsia

       N Engl J Med. 2016 Jan 7;374(1):13-22. Link

2.    Pregnancy Outcomes after Clinical Recovery from AKI

        J Am Soc Nephrol. 2017 May;28(5):1566-1574. Link

3.      Removal of Soluble Fms-Like Tyrosine Kinase-1 by Dextran Sulfate Apheresis in Preeclampsia

        J Am Soc Nephrol. 2016 Mar;27(3):903-13. Link

#AskASN introduction by Anna Burgner