why do we get natriuresis with SGLT2i?

Could it just be the simple fact that the 'S' in SGLT2i stands for sodium - so blocking sodium reabsorbtion in PT = natriuresis?

Alicia McDonough robs me of that simplistic thinking at the #KidneyWk talk on this (h/t @VelezNephHepato)

Firstly, SGLT2i can increase even the paracellular Na *secretion*
From this @CO_Neph_Hype review https://pubmed.ncbi.nlm.nih.gov/31815757/ 

#KidneyWk

But most of her talk was focused on the NHE3, colacalized with SGLT2i on the proximal tubule

(note the SGLT2i in use have a little bit SGLT1 inhibition - the one with the most Sotagliflozin RCT SCORED will be at AHA)

#KidneyWk

NHE3 reabsorbs Na; the H+ gets recycled
so inhibition of NHE3 = more natriuresis

so SGLT2i inhibition of NHE3 would make a lot of sense. How does it occur? SOme intriguing data on MAP17 mediation here https://journals.physiology.org/doi/abs/10.1152/ajpcell.00275.2019?journalCode=ajpcell

#KidneyWk

More here https://pubmed.ncbi.nlm.nih.gov/32893663/  in @AJPRenal

(as an aside NHE3 also causes more bicarbonaturia - which is how NHE3 activity is measured)

#KidneyWK

This role of NHE3 inhibition in the proximal tubule may also be significant in heart failure as shown in this @biorxivpreprint https://www.biorxiv.org/content/10.1101/2020.07.16.207118v1.full

#KidneyWK

She recommends this nice review in @hyperaha https://pubmed.ncbi.nlm.nih.gov/32114848/  from Chris Wilcox which puts most things we know about the topic together nicely

#KidneyWk

As an aside Dr McDonough kept calling these 'gliflozins' or 'flozins'

I am liking the 'flozins' instead of the clunky SGLT2i

WHat say #KidneyWK peeps?