Thread by @priti899

SGLT2i 💊 are emerging as a promising agent to prevent and ⤵️the progression of DKD
Ever wondered
What do they do to electrolytes❓
Why r these diuretics not associated with electrolyte depletion❓

Let's dive deeper🔓
#medtwitter #NephMadness #SGLT2iRegion

What is the impact of SGLT2i on Na and water hemostasis?

First, let’s revisit, how Na and glucose are handled in the nephron 📜
💥100% of the filtered glucose is reabsorbed along the nephron (90%, via SGLT2 in PCT)
💥1 Na+ ion for every glucose molecule gets absorbed from the lumen
💥In PCT 60 - 80% of sodium is reabsorbed

Now let’s find out what happens with SGLT2 inhibition❓

⚡️⚡️ With SGLT2 inhibition in PCT, Na/glucose, pass distally ➡️↑ delivery of Na to macula densa ➡️vasoconstriction of afferent artery and Natriuresis and glycosuria

⭐️Although negative Na balance, there are NO changes in serum Na levels in clinical studies.
👀Notice anything odd?
⚡️Possible mechanism: Due to the redistribution of Na from intracellular to extracellular spaces.
ncbi.nlm.nih.gov/pmc/articles/P…

What is the effect of SGLT2i on serum K levels?

💥Slight ⬆️ in K ( 0.6 - 2.8%) was found in some SGLT2i trials with 💊canagliflozin (not with empagliflozin and dapagliflozin )

📎doi.org/10.1185/030079…

💥Although ⬆️ in K is small, careful monitoring is required in patients with⚖️
⭐️CKD
⭐️Patients taking concomitant medications associated with ↑ K level (k sparing diuretics/ RAAS blockers )

💥Mechanism of hyperkalemia 👇👇

⚡️Diuresis-associated hemoconcentration
⚡️Decrease insulin secretion→ shift to extracellular fluid

What is the effect of SGLT2i on serum Phosphate levels?

let’s try to understand the effect of SGLT2i on PO4 homeostasis.
⚡️SGLT2 Inhibition➡️ ↓ Proximal Na reabsorption ➡️↑availability of Na to be reabsorbed with PO4 via the NaPi IIa co-transporter in PCT.

A recent study with dapagliflozin for 6 weeks showed
⭐️↑ S Po4 levels - 9%
⭐️↑ FGF‐23 -19%
⭐️↑ PTH -16%
ncbi.nlm.nih.gov/pubmed/3055910…

💥👇In conclusion
FGF23 is stimulated by ⬆️ S Po4 levels → phosphaturia and ↓ 1,25(OH)2 D and ↑ PTH to maintain the phosphate balance

thelancet.com/journals/landi…

what is the effect of SGLT2i on Mg hemostasis?

lets first establish what happens to serum Mg levels in DM?

⚡️Insulin regulates expression of the TRPM6 Mg2+ channel in DCT
⚡️Insulin resistance ➡️ ↓TRMP6 activity in DCT Renal Mg wasting-induced hypomagnesemia

diabetes.diabetesjournals.org/content/65/1/3…

SGLT2i leads to:
⭐️Reduction of insulin resistance
⭐️↓ Mg excretion through TRPM6
⭐️Natriuresis /osmotic diuresis ➡️ ↓ECV ➡️ hemoconcentration ➡️Mg redistribution to ECV.

🔥Net effects of SGLT2i → ↑ Mg levels

ncbi.nlm.nih.gov/pubmed/27628105

But how significant is this hyperMg?👀

💥According to a meta-analysis, SGLT2i ↑ S Mg levels by 0.08–0.2 mEq/ L.

📎link.springer.com/article/10.100…
Check out this fig.👇

Before finishing, let's summarize
💥SGLT2 inhibition → Glycosuria, natriuresis, and osmotic diuresis
✔️Slight ↑ serum K and Mg levels
✔️↑Pi → ↑FGF23→ ↓ 1,25(OH)2 D and ↑ PTH

👉asbmr.onlinelibrary.wiley.com/doi/pdf/10.100…

Check out more on SGLT2i ajkdblog.org/2020/03/13/nep…