Thread by @kdjhaveri

Post Grand Rounds SLGT2i and the Kidney Tweetorial
- The Glucoretics - thanks @edgarvlermamd @ChristosArgyrop @jam_hirsch for some slides
Start...PART 1 nature.com/articles/s4158…

SGLT2 is responsible for reabsorbing up to 90% (animal data) of the glucose filtered at the glomerulus. The remaining 10% (animal data) is reabsorbed by SGLT1 that is expressed on the luminal (brush border) surface of cells of the S3 segment of the proximal tubule

Pathophysiology of Diabetic Nephropathy and role of SGLT2

Glomerular hyperfiltration over a long period of time is associated with podocyte stress and loss.
Over a period of time podocyte loss leads to glomerulosclerosis and atrophy

"We should be paying more attention to the proximal tubule" @ChristosArgyrop

A picture says a 1000 words-- the magic word is decreasing hyperfiltration

Now ACEi/ARB + SGLT2i are #BFF slide courtesy @renalmyeloma

What has been approved?

Credence- Amazing renal outcomes/ despite GFR @NEJM @CJASN

DAPA-CKD- look at the ODDS ratios!!

The Kidneys are in for some protections-- time to #flozinate

A must read for all that summarizes all major renal trials onlinelibrary.wiley.com/doi/full/10.10… @ChristosArgyrop

No major issues with biomarkers as well

Next up; Glomerular diseases: Dapa CKD had a good amount of patients with Glomerular diseases. More IgA patients than any large IgA neph trial..

What time is it? -- time to flozinate-- Look at this amazing IgAN response..

Next up- definite cardiorenal benefit as we all saw- so if lasix doesn't work, and thiazides don't do much- add SGLT2i for your cardiorenal patient

Mechanism of Cardiorenal benefit- unclear

Next up- Hypomagnesemia-- more wow!!
Just keep coming along!! ncbi.nlm.nih.gov/pmc/articles/P…

Why? maybe.. Increase glucagon levels– increase mg absorption in the distal tubule; Decrease in insulin levels – leading to movement of Mg to extracellular volume; Hemoconcentration related?; Reduced Mg excretion-effect on ion channel 6; insulin resistant effect on mg wasting

Next up- SIADH--- with empa @JASN_News jasn.asnjournals.org/content/31/3/6…

Next up- SGLT2i also prevent AKI compared to other anti diabetic agents--- hmmm cjasn.asnjournals.org/content/16/1/7…

What else can they do? Improve Anemia in CKD
More EPO production as less effect of #hif

For the #onconephrology world- basic science study canagliflozin significantly attenuates cisplatin-induced nephropathy in C57BL/6 mice and suppresses cisplatin induced renal proximal tubular cell apoptosis in vitro. journals.physiology.org/doi/full/10.11…

Large analysis showing less kidney stones @weddellite @DMalieckal --- hmmm #flozinate for stone prevention..maybe the increase urine flow, decreased uric acid levels increased fluid intake by patients given being on SGLT2i link.springer.com/article/10.100… END PART 1

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