Thread by @priti899, SGLT2i are emerging as a promising agent to prevent and the [...]

SGLT2i

https://abs.twimg.com/emoji/v2/... draggable="false" alt="💊" title="Pill" aria-label="Emoji: Pill"> are emerging as a promising agent to prevent and

https://abs.twimg.com/emoji/v2/... draggable="false" alt="⤵️" title="Arrow pointing rightwards then curving downwards" aria-label="Emoji: Arrow pointing rightwards then curving downwards">the progression of DKD
Ever wondered
What do they do to electrolytes

https://abs.twimg.com/emoji/v2/... draggable="false" alt="❓" title="Red question mark ornament" aria-label="Emoji: Red question mark ornament">
Why r these diuretics not associated with electrolyte depletion

https://abs.twimg.com/emoji/v2/... draggable="false" alt="❓" title="Red question mark ornament" aria-label="Emoji: Red question mark ornament">

Let& #39;s dive deeper

https://abs.twimg.com/emoji/v2/... draggable="false" alt="🔓" title="Open lock" aria-label="Emoji: Open lock">
#medtwitter #NephMadness #SGLT2iRegion

SGLT2i https://abs.twimg.com/emoji/v2/... draggable=

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

First, let’s revisit, how Na and glucose are handled in the nephron

https://abs.twimg.com/emoji/v2/... draggable="false" alt="📜" title="Scroll" aria-label="Emoji: Scroll">

https://abs.twimg.com/emoji/v2/... draggable="false" alt="💥" title="Collision symbol" aria-label="Emoji: Collision symbol">100% of the filtered glucose is reabsorbed along the nephron (90%, via SGLT2 in PCT)

https://abs.twimg.com/emoji/v2/... draggable="false" alt="💥" title="Collision symbol" aria-label="Emoji: Collision symbol">1 Na+ ion for every glucose molecule gets absorbed from the lumen

https://abs.twimg.com/emoji/v2/... draggable="false" alt="💥" title="Collision symbol" aria-label="Emoji: Collision symbol">In PCT 60 - 80% of sodium is reabsorbed

First, let’s revisit, how Na and glucose are handled in the nephron https://abs.twimg.com/emoji/v2/... draggable=

https://abs.twimg.com/emoji/v2/... draggable="false" alt="💥" title="Collision symbol" aria-label="Emoji: Collision symbol">100% of the filtered glucose is reabsorbed along the nephron (90%, via SGLT2 in PCT) https://abs.twimg.com/emoji/v2/... draggable="false" alt="💥" title="Collision symbol" aria-label="Emoji: Collision symbol">1 Na+ ion for every glucose molecule gets absorbed from the lumen https://abs.twimg.com/emoji/v2/... draggable="false" alt="💥" title="Collision symbol" aria-label="Emoji: Collision symbol">In PCT 60 - 80% of sodium is reabsorbed" title="First, let’s revisit, how Na and glucose are handled in the nephron https://abs.twimg.com/emoji/v2/... draggable="false" alt="📜" title="Scroll" aria-label="Emoji: Scroll"> https://abs.twimg.com/emoji/v2/... draggable="false" alt="💥" title="Collision symbol" aria-label="Emoji: Collision symbol">100% of the filtered glucose is reabsorbed along the nephron (90%, via SGLT2 in PCT) https://abs.twimg.com/emoji/v2/... draggable="false" alt="💥" title="Collision symbol" aria-label="Emoji: Collision symbol">1 Na+ ion for every glucose molecule gets absorbed from the lumen https://abs.twimg.com/emoji/v2/... draggable="false" alt="💥" title="Collision symbol" aria-label="Emoji: Collision symbol">In PCT 60 - 80% of sodium is reabsorbed" class="img-responsive" style="max-width:100%;"/>

Now let’s find out what happens with SGLT2 inhibition

https://abs.twimg.com/emoji/v2/... draggable="false" alt="❓" title="Red question mark ornament" aria-label="Emoji: Red question mark ornament">

https://abs.twimg.com/emoji/v2/... draggable="false" alt="⚡️" title="High voltage sign" aria-label="Emoji: High voltage sign">

https://abs.twimg.com/emoji/v2/... draggable="false" alt="⚡️" title="High voltage sign" aria-label="Emoji: High voltage sign"> With SGLT2 inhibition in PCT, Na/glucose, pass distally

https://abs.twimg.com/emoji/v2/... draggable="false" alt="➡️" title="Rightwards arrow" aria-label="Emoji: Rightwards arrow">↑ delivery of Na to macula densa

https://abs.twimg.com/emoji/v2/... draggable="false" alt="➡️" title="Rightwards arrow" aria-label="Emoji: Rightwards arrow">vasoconstriction of afferent artery and Natriuresis and glycosuria

Now let’s find out what happens with SGLT2 inhibitionhttps://abs.twimg.com/emoji/v2/... draggable=

https://abs.twimg.com/emoji/v2/... draggable="false" alt="⭐️" title="Medium star" aria-label="Emoji: Medium star">Although negative Na balance, there are NO changes in serum Na levels in clinical studies.

https://abs.twimg.com/emoji/v2/... draggable="false" alt="👀" title="Eyes" aria-label="Emoji: Eyes">Notice anything odd?

https://abs.twimg.com/emoji/v2/... draggable="false" alt="⚡️" title="High voltage sign" aria-label="Emoji: High voltage sign">Possible mechanism: Due to the redistribution of Na from intracellular to extracellular spaces. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4839176/">https://www.ncbi.nlm.nih.gov/pmc/artic...

SGLT2 Inhibitors and Cardiovascular Risk: Lessons Learned From the EMPA-REG OUTCOME Study

Although cardiovascular (CV) mortality is the principal cause of death in individuals with type 2 diabetes (T2DM), reduction of plasma glucose concentration has little effect on CV disease (CVD)...

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

What is the effect of SGLT2i on serum K levels?

https://abs.twimg.com/emoji/v2/... draggable="false" alt="💥" title="Collision symbol" aria-label="Emoji: Collision symbol">Slight

https://abs.twimg.com/emoji/v2/... draggable="false" alt="⬆️" title="Upwards arrow" aria-label="Emoji: Upwards arrow"> in K ( 0.6 - 2.8%) was found in some SGLT2i trials with

https://abs.twimg.com/emoji/v2/... draggable="false" alt="💊" title="Pill" aria-label="Emoji: Pill">canagliflozin (not with empagliflozin and dapagliflozin )

https://abs.twimg.com/emoji/v2/... draggable="false" alt="📎" title="Paperclip" aria-label="Emoji: Paperclip"> https://doi.org/10.1185/03007995.2014.919907">https://doi.org/10.1185/0...

Slight https://abs.twimg.com/emoji/v2/... draggable="false" alt="⬆️" title="Upwards arrow" aria-label="Emoji: Upwards arrow"> in K ( 0.6 - 2.8%) was found in some SGLT2i trials with https://abs.twimg.com/emoji/v2/... draggable="false" alt="💊" title="Pill" aria-label="Emoji: Pill">canagliflozin (not with empagliflozin and dapagliflozin ) https://abs.twimg.com/emoji/v2/... draggable="false" alt="📎" title="Paperclip" aria-label="Emoji: Paperclip"> https://doi.org/10.1185/0..." title="https://abs.twimg.com/emoji/v2/... draggable="false" alt="💥" title="Collision symbol" aria-label="Emoji: Collision symbol">Slight https://abs.twimg.com/emoji/v2/... draggable="false" alt="⬆️" title="Upwards arrow" aria-label="Emoji: Upwards arrow"> in K ( 0.6 - 2.8%) was found in some SGLT2i trials with https://abs.twimg.com/emoji/v2/... draggable="false" alt="💊" title="Pill" aria-label="Emoji: Pill">canagliflozin (not with empagliflozin and dapagliflozin ) https://abs.twimg.com/emoji/v2/... draggable="false" alt="📎" title="Paperclip" aria-label="Emoji: Paperclip"> https://doi.org/10.1185/0..." class="img-responsive" style="max-width:100%;"/>

https://abs.twimg.com/emoji/v2/... draggable="false" alt="💥" title="Collision symbol" aria-label="Emoji: Collision symbol">Although

https://abs.twimg.com/emoji/v2/... draggable="false" alt="⬆️" title="Upwards arrow" aria-label="Emoji: Upwards arrow"> in K is small, careful monitoring is required in patients with

https://abs.twimg.com/emoji/v2/... draggable="false" alt="⚖️" title="Scales" aria-label="Emoji: Scales">

https://abs.twimg.com/emoji/v2/... draggable="false" alt="⭐️" title="Medium star" aria-label="Emoji: Medium star">CKD

https://abs.twimg.com/emoji/v2/... draggable="false" alt="⭐️" title="Medium star" aria-label="Emoji: Medium star">Patients taking concomitant medications associated with ↑ K level (k sparing diuretics/ RAAS blockers )

https://abs.twimg.com/emoji/v2/... draggable="false" alt="💥" title="Collision symbol" aria-label="Emoji: Collision symbol">Mechanism of hyperkalemia

https://abs.twimg.com/emoji/v2/... draggable="false" alt="👇" title="Down pointing backhand index" aria-label="Emoji: Down pointing backhand index">

https://abs.twimg.com/emoji/v2/... draggable="false" alt="⚡️" title="High voltage sign" aria-label="Emoji: High voltage sign">Diuresis-associated hemoconcentration

https://abs.twimg.com/emoji/v2/... draggable="false" alt="⚡️" title="High voltage sign" aria-label="Emoji: High voltage sign">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.

https://abs.twimg.com/emoji/v2/... draggable="false" alt="⚡️" title="High voltage sign" aria-label="Emoji: High voltage sign">SGLT2 Inhibition

https://abs.twimg.com/emoji/v2/... draggable="false" alt="➡️" title="Rightwards arrow" aria-label="Emoji: Rightwards arrow"> ↓ Proximal Na reabsorption

https://abs.twimg.com/emoji/v2/... draggable="false" alt="➡️" title="Rightwards arrow" aria-label="Emoji: Rightwards arrow">↑availability of Na to be reabsorbed with PO4 via the NaPi IIa co-transporter in PCT.

let’s try to understand the effect of SGLT2i on PO4 homeostasis.https://abs.twimg.com/emoji/v2/... draggable=

SGLT2 Inhibitionhttps://abs.twimg.com/emoji/v2/... draggable="false" alt="➡️" title="Rightwards arrow" aria-label="Emoji: Rightwards arrow"> ↓ Proximal Na reabsorption https://abs.twimg.com/emoji/v2/... draggable="false" alt="➡️" title="Rightwards arrow" aria-label="Emoji: Rightwards arrow">↑availability of Na to be reabsorbed with PO4 via the NaPi IIa co-transporter in PCT." title="let’s try to understand the effect of SGLT2i on PO4 homeostasis.https://abs.twimg.com/emoji/v2/... draggable="false" alt="⚡️" title="High voltage sign" aria-label="Emoji: High voltage sign">SGLT2 Inhibitionhttps://abs.twimg.com/emoji/v2/... draggable="false" alt="➡️" title="Rightwards arrow" aria-label="Emoji: Rightwards arrow"> ↓ Proximal Na reabsorption https://abs.twimg.com/emoji/v2/... draggable="false" alt="➡️" title="Rightwards arrow" aria-label="Emoji: Rightwards arrow">↑availability of Na to be reabsorbed with PO4 via the NaPi IIa co-transporter in PCT." class="img-responsive" style="max-width:100%;"/>

A recent study with dapagliflozin for 6 weeks showed

https://abs.twimg.com/emoji/v2/... draggable="false" alt="⭐️" title="Medium star" aria-label="Emoji: Medium star">↑ S Po4 levels - 9%

https://abs.twimg.com/emoji/v2/... draggable="false" alt="⭐️" title="Medium star" aria-label="Emoji: Medium star">↑ FGF‐23 -19%

https://abs.twimg.com/emoji/v2/... draggable="false" alt="⭐️" title="Medium star" aria-label="Emoji: Medium star">↑ PTH -16%
https://www.ncbi.nlm.nih.gov/pubmed/30559106?dopt=Abstract">https://www.ncbi.nlm.nih.gov/pubmed/30...

https://abs.twimg.com/emoji/v2/... draggable="false" alt="💥" title="Collision symbol" aria-label="Emoji: Collision symbol">

https://abs.twimg.com/emoji/v2/... draggable="false" alt="👇" title="Down pointing backhand index" aria-label="Emoji: Down pointing backhand index">In conclusion
FGF23 is stimulated by

https://abs.twimg.com/emoji/v2/... draggable="false" alt="⬆️" title="Upwards arrow" aria-label="Emoji: Upwards arrow"> 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">https://www.thelancet.com/journals/...

https://abs.twimg.com/emoji/v2/... draggable="false" alt="👇" title="Down pointing backhand index" aria-label="Emoji: Down pointing backhand index">In conclusion FGF23 is stimulated by https://abs.twimg.com/emoji/v2/... draggable="false" alt="⬆️" title="Upwards arrow" aria-label="Emoji: Upwards arrow"> S Po4 levels → phosphaturia and ↓ 1,25(OH)2 D and ↑ PTH to maintain the phosphate balance https://www.thelancet.com/journals/..." title="https://abs.twimg.com/emoji/v2/... draggable="false" alt="💥" title="Collision symbol" aria-label="Emoji: Collision symbol">https://abs.twimg.com/emoji/v2/... draggable="false" alt="👇" title="Down pointing backhand index" aria-label="Emoji: Down pointing backhand index">In conclusion FGF23 is stimulated by https://abs.twimg.com/emoji/v2/... draggable="false" alt="⬆️" title="Upwards arrow" aria-label="Emoji: Upwards arrow"> S Po4 levels → phosphaturia and ↓ 1,25(OH)2 D and ↑ PTH to maintain the phosphate balance https://www.thelancet.com/journals/..." class="img-responsive" style="max-width:100%;"/>

what is the effect of SGLT2i on Mg hemostasis?

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

https://abs.twimg.com/emoji/v2/... draggable="false" alt="⚡️" title="High voltage sign" aria-label="Emoji: High voltage sign">Insulin regulates expression of the TRPM6 Mg2+ channel in DCT

https://abs.twimg.com/emoji/v2/... draggable="false" alt="⚡️" title="High voltage sign" aria-label="Emoji: High voltage sign">Insulin resistance

https://abs.twimg.com/emoji/v2/... draggable="false" alt="➡️" title="Rightwards arrow" aria-label="Emoji: Rightwards arrow"> ↓TRMP6 activity in DCT Renal Mg wasting-induced hypomagnesemia

https://diabetes.diabetesjournals.org/content/65/1/3.figures-only">https://diabetes.diabetesjournals.org/content/6...

lets first establish what happens to serum Mg levels in DM?https://abs.twimg.com/emoji/v2/... draggable=

Insulin regulates expression of the TRPM6 Mg2+ channel in DCThttps://abs.twimg.com/emoji/v2/... draggable="false" alt="⚡️" title="High voltage sign" aria-label="Emoji: High voltage sign">Insulin resistance https://abs.twimg.com/emoji/v2/... draggable="false" alt="➡️" title="Rightwards arrow" aria-label="Emoji: Rightwards arrow"> ↓TRMP6 activity in DCT Renal Mg wasting-induced hypomagnesemia https://diabetes.diabetesjournals.org/content/6..." title="lets first establish what happens to serum Mg levels in DM?https://abs.twimg.com/emoji/v2/... draggable="false" alt="⚡️" title="High voltage sign" aria-label="Emoji: High voltage sign">Insulin regulates expression of the TRPM6 Mg2+ channel in DCThttps://abs.twimg.com/emoji/v2/... draggable="false" alt="⚡️" title="High voltage sign" aria-label="Emoji: High voltage sign">Insulin resistance https://abs.twimg.com/emoji/v2/... draggable="false" alt="➡️" title="Rightwards arrow" aria-label="Emoji: Rightwards arrow"> ↓TRMP6 activity in DCT Renal Mg wasting-induced hypomagnesemia https://diabetes.diabetesjournals.org/content/6..." class="img-responsive" style="max-width:100%;"/>

SGLT2i leads to:

https://abs.twimg.com/emoji/v2/... draggable="false" alt="⭐️" title="Medium star" aria-label="Emoji: Medium star">Reduction of insulin resistance

https://abs.twimg.com/emoji/v2/... draggable="false" alt="⭐️" title="Medium star" aria-label="Emoji: Medium star">↓ Mg excretion through TRPM6

https://abs.twimg.com/emoji/v2/... draggable="false" alt="⭐️" title="Medium star" aria-label="Emoji: Medium star">Natriuresis /osmotic diuresis

https://abs.twimg.com/emoji/v2/... draggable="false" alt="➡️" title="Rightwards arrow" aria-label="Emoji: Rightwards arrow"> ↓ECV

https://abs.twimg.com/emoji/v2/... draggable="false" alt="➡️" title="Rightwards arrow" aria-label="Emoji: Rightwards arrow"> hemoconcentration

https://abs.twimg.com/emoji/v2/... draggable="false" alt="➡️" title="Rightwards arrow" aria-label="Emoji: Rightwards arrow">Mg redistribution to ECV.

https://abs.twimg.com/emoji/v2/... draggable="false" alt="🔥" title="Fire" aria-label="Emoji: Fire">Net effects of SGLT2i → ↑ Mg levels

https://www.ncbi.nlm.nih.gov/pubmed/27628105 ">https://www.ncbi.nlm.nih.gov/pubmed/27...

SGLT2i leads to:https://abs.twimg.com/emoji/v2/... draggable=

But how significant is this hyperMg?

https://abs.twimg.com/emoji/v2/... draggable="false" alt="👀" title="Eyes" aria-label="Emoji: Eyes">

https://abs.twimg.com/emoji/v2/... draggable="false" alt="💥" title="Collision symbol" aria-label="Emoji: Collision symbol">According to a meta-analysis, SGLT2i ↑ S Mg levels by 0.08–0.2 mEq/ L.

https://abs.twimg.com/emoji/v2/... draggable="false" alt="📎" title="Paperclip" aria-label="Emoji: Paperclip"> https://link.springer.com/article/10.1007%2Fs00125-016-4101-6
Check">https://link.springer.com/article/1... out this fig.

https://abs.twimg.com/emoji/v2/... draggable="false" alt="👇" title="Down pointing backhand index" aria-label="Emoji: Down pointing backhand index">

But how significant is this hyperMg?https://abs.twimg.com/emoji/v2/... draggable=

https://abs.twimg.com/emoji/v2/... draggable="false" alt="💥" title="Collision symbol" aria-label="Emoji: Collision symbol">According to a meta-analysis, SGLT2i ↑ S Mg levels by 0.08–0.2 mEq/ L.https://abs.twimg.com/emoji/v2/... draggable="false" alt="📎" title="Paperclip" aria-label="Emoji: Paperclip"> https://link.springer.com/article/1... out this fig.https://abs.twimg.com/emoji/v2/... draggable="false" alt="👇" title="Down pointing backhand index" aria-label="Emoji: Down pointing backhand index">" title="But how significant is this hyperMg?https://abs.twimg.com/emoji/v2/... draggable="false" alt="👀" title="Eyes" aria-label="Emoji: Eyes">https://abs.twimg.com/emoji/v2/... draggable="false" alt="💥" title="Collision symbol" aria-label="Emoji: Collision symbol">According to a meta-analysis, SGLT2i ↑ S Mg levels by 0.08–0.2 mEq/ L.https://abs.twimg.com/emoji/v2/... draggable="false" alt="📎" title="Paperclip" aria-label="Emoji: Paperclip"> https://link.springer.com/article/1... out this fig.https://abs.twimg.com/emoji/v2/... draggable="false" alt="👇" title="Down pointing backhand index" aria-label="Emoji: Down pointing backhand index">" class="img-responsive" style="max-width:100%;"/>

Before finishing, let& #39;s summarize

https://abs.twimg.com/emoji/v2/... draggable="false" alt="💥" title="Collision symbol" aria-label="Emoji: Collision symbol">SGLT2 inhibition → Glycosuria, natriuresis, and osmotic diuresis

https://abs.twimg.com/emoji/v2/... draggable="false" alt="✔️" title="Heavy check mark" aria-label="Emoji: Heavy check mark">Slight ↑ serum K and Mg levels

https://abs.twimg.com/emoji/v2/... draggable="false" alt="✔️" title="Heavy check mark" aria-label="Emoji: Heavy check mark">↑Pi → ↑FGF23→ ↓ 1,25(OH)2 D and ↑ PTH

https://abs.twimg.com/emoji/v2/... draggable="false" alt="👉" title="Right pointing backhand index" aria-label="Emoji: Right pointing backhand index"> https://asbmr.onlinelibrary.wiley.com/doi/pdf/10.1002/jbm4.10242">https://asbmr.onlinelibrary.wiley.com/doi/pdf/1...

Before finishing, let& #39;s summarizehttps://abs.twimg.com/emoji/v2/... draggable=

SGLT2 inhibition → Glycosuria, natriuresis, and osmotic diuresishttps://abs.twimg.com/emoji/v2/... draggable="false" alt="✔️" title="Heavy check mark" aria-label="Emoji: Heavy check mark">Slight ↑ serum K and Mg levels https://abs.twimg.com/emoji/v2/... draggable="false" alt="✔️" title="Heavy check mark" aria-label="Emoji: Heavy check mark">↑Pi → ↑FGF23→ ↓ 1,25(OH)2 D and ↑ PTH https://abs.twimg.com/emoji/v2/... draggable="false" alt="👉" title="Right pointing backhand index" aria-label="Emoji: Right pointing backhand index"> https://asbmr.onlinelibrary.wiley.com/doi/pdf/1..." title="Before finishing, let& #39;s summarizehttps://abs.twimg.com/emoji/v2/... draggable="false" alt="💥" title="Collision symbol" aria-label="Emoji: Collision symbol">SGLT2 inhibition → Glycosuria, natriuresis, and osmotic diuresishttps://abs.twimg.com/emoji/v2/... draggable="false" alt="✔️" title="Heavy check mark" aria-label="Emoji: Heavy check mark">Slight ↑ serum K and Mg levels https://abs.twimg.com/emoji/v2/... draggable="false" alt="✔️" title="Heavy check mark" aria-label="Emoji: Heavy check mark">↑Pi → ↑FGF23→ ↓ 1,25(OH)2 D and ↑ PTH https://abs.twimg.com/emoji/v2/... draggable="false" alt="👉" title="Right pointing backhand index" aria-label="Emoji: Right pointing backhand index"> https://asbmr.onlinelibrary.wiley.com/doi/pdf/1..." class="img-responsive" style="max-width:100%;"/>

Check out more on SGLT2i https://ajkdblog.org/2020/03/13/nephmadness-2020-sglt2i-region/">https://ajkdblog.org/2020/03/1...

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