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. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4839176/

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 )

https://doi.org/10.1185/03007995.2014.919907

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%
https://www.ncbi.nlm.nih.gov/pubmed/30559106?dopt=Abstract

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

https://www.thelancet.com/journals/landia/article/PIIS2213-8587(14)70227-X/fulltext

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

https://diabetes.diabetesjournals.org/content/65/1/3.figures-only

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

https://www.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.

https://link.springer.com/article/10.1007%2Fs00125-016-4101-6
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

https://asbmr.onlinelibrary.wiley.com/doi/pdf/10.1002/jbm4.10242

Check out more on SGLT2i https://ajkdblog.org/2020/03/13/nephmadness-2020-sglt2i-region/