Thread by @KIReports

📢📢Tweetorial Alert📢📢 1/14
What are the benefits of Sodium-Glucose Cotransporter-2 inhibitors (SGLT2i)?

All of the above?
#Flozinators we know #flozins are great & are beneficial in CKD & CV disease, but do they really prevent kidney stones?
How do they work? Does it have anything to do with their effects on magnesium or uric acid? Does the presence of DM make a difference?

Stone formation risk ↑ in DM:
↑ uric acid excretion💎
Impaired ammoniagenesis
↓ in urinary pH levels
Dehydration with urinary concentration 🥤
@Momen_Abbasi
renalfellow.org/2023/02/19/kid…

Empagliflozin ↓ urolithiasis risk by approximately 40% in a pooled analysis of randomized clinical trials.
In contrast, another report showed that the adverse effects of SGLT2i might include ↑ nephrolithiasis risk?
ncbi.nlm.nih.gov/pmc/articles/P…

Potential Mechanisms
SGLT2i ↑ urinary pH by inhibiting Na-H exchanger & bicarbonate reabsorption in the proximal tubule.
SGLT2i ↓ urinary uric acid & Mg, both of which may act as a nidus for stone formation.
Further studies are needed to elucidate mechanisms.

In this @KIReports study, the relationship between several antidiabetic medications & the likelihood of developing urolithiasis in patients with/without DM was explored using a large-scale epidemiologic Japanese database - 1 million patients.
kireports.org/article/S2468-…

Cross-sectional study
Data collection from 1/1/21 to 12/31/21.
Urolithiasis was common in patients with DM:
OR, 1.12; 95% confidence interval [CI], 1.10–1.13 for males
OR, 1.70; 95% CI, 1.67–1.73 for females

Next, they compared the patient use of several different diabetes meds with patients who did not use these meds.
Only the use of SGLT2i was negatively associated with urolithiasis (OR, 0.95; 95% CI, 0.91–0.98: male & OR, 0.91; 95% CI, 0.86–0.97: female)

Patients Without DM
In ♂, SGLT2i use without DM was associated with a low likelihood of urolithiasis (OR, 0.42; 95% CI, 0.35–0.51).
In contrast, in ♀, SGLT2i use without DM was not significantly associated with a low likelihood of urolithiasis (OR, 0.90; 95% CI, 0.68–1.19).

Study Weaknesses
Couldn’t examine other risks (obesity or HTN) in this database.
Cross-sectional study can’t determine a causal relationship between meds & nephrolithiasis.
Further prospective observational studies are needed-SWEETSTONE is pending.
pubmed.ncbi.nlm.nih.gov/35288397/

Conclusions
A novel finding in this study was that SGLT2i use predicted a low likelihood of urolithiasis, whereas use of other antidiabetic medications were associated with an increased likelihood of developing urolithiasis.

Conclusions
SGLT2i were associated with a low likelihood of urolithiasis in ♂️ with/without DM. Findings in ♀️ were only significant for patients with DM.
In vivo & in vitro studies suggest that SGLT2i prevent stone formation via anti-inflammatory & anti-fibrotic effects.

This has been @brian_rifkin with another KI Reports tweetorial.
Keep Calm and #Flozinate On👑🪨 🪨 🪨 🪨!