Sodium/Glucose Cotransporter 2 Inhibition and Urolithiasis: The Effect of Urinary pH and Citrate
Abstract
To the Editor: In a cross-sectional study of Japanese patients with diabetes, Anan et al. found that the use of sodium/glucose cotransporter 2 inhibitors (SGLT2is) was associated with reduced odds of urolithiasis compared to the use of other antidiabetics. They also showed reduced odds of urolithiasis among male patients without diabetes, who were prescribed SGLT2is. This finding is in line with other published studies. Anan et al. argue that a possible mechanism explaining this risk reduction might be an increase in urinary pH on SGLT2 inhibition. However, this assumption is not based on data and no citation of the literature is provided. In contrast, in our post hoc analysis of a trial with 45 healthy volunteers, we showed a decrease in urinary pH and an increase in urinary citrate on empagliflozin (an SLGT2i) treatment over 4 weeks, which resulted in reduced supersaturation ratios of calciumphosphate minerals. We hypothesize that the decrease in urinary pH and the increase in urinary citrate, possibly resulting from decreased ammoniagenesis in proximal tubule, drive the protective effect of SGLT2is on nephrolithiasis, especially for calcium-phosphate containing stones. However, this hypothesis needs to be tested in a trial performed in stone formers.
How strong is the evidence?
Evidence Hub reads this as a cross-sectional, done in people. Its evidence level is 4 of 5 (Low · observational). Observational designs can show an association but not prove cause. Reported size: 45 participants or records.
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