Topic Discussion: Hypertension and TMA- chicken or the egg?

A recent discussion on twitter and ASN Communities has sparked this age old battle if HTN related TMA exists? Some believe that TMA is the initial insult and that leads to endothelial damage and HTN is a symptom and not the disease. Some believe that HTN is the start - leading to sheer stress and endothelial damage and in severe cases-- TMA

Does having chronic or acute hypertension cause endothelial damage and TMA or does TMA cause endothelial damage and HTN as a result? @purvasharma821 @KidneyKhanin @VBijol @renalmyeloma @NephRodby @GlassockJ

— Kenar Jhaveri (@kdjhaveri) January 15, 2020

Check out the amazing twitter discussion by TMA experts on this topic.
What i found was this amazing image

As one can see in this image- with some data existing on this - that malignant HTN can lead to endothelial dysfunction and some complement activation but not as severe as aHUS.

So if HTN does cause TMA, how does one distinguish that from a complement mediated TMA or aHUS? What if we are missing a mutation or an antibody that we haven't discovered.

1) Kidney biopsy cannot distinguish HTN induced TMA from complement mediated TMA 2) C3 being low is more valuable for an over active complement cascade compared to C5b-9 as even HTN can cause that to be elevated
3)) Doing a fundus exam can help significantly- there is no value in genetic testing in grade 3/4 retinopathy and especially with DBP>130mm Hg 4) No value in genetic testing in those that have a good response to bp control and eventually stabilized kidney function.
5) Ongoing TMA despite bp control and recovering of renal function- likely is then not HTN mediated and additional complement testing should be done.