The Author Replies:
We thank Harmacek D. and Bonny O. for their interest in our study “Impact of sodium-glucose cotransporter-2 inhibitors on urolithiasis.”1 They conducted a trial with healthy volunteers and found that sodium-glucose cotransporter-2 (SGLT2) inhibitor decreased urinary pH and increased urinary citrate, compared to the effect of empagliflozin and placebo over 4 weeks.2 This study was performed in healthy volunteers instead of patients with urolithiasis. SGLT2 inhibitor possibly increases urinary citrate, which can prevent kidney stone recurrence.
Urine of acidic pH is a common symptom presented by patients and rats with urolithiasis.3, 4 SGLT2 inhibitors increase urinary pH because of the inhibition of Na+-H+ exchanger and bicarbonate reabsorption in the proximal tubules.S1–S3 In our study, urinary pH of ethylene glycol induced rats with renal calcium oxalate stone formation was significantly lowered than that of control rats.4 In addition, phlorizin (SGLT1/2 inhibitor) treatment significantly elevated urinary pH as compared to that in rats with renal calcium oxalate stone formation.4 This can affect calcium oxalate crystal adhesion to tubular surfaces, because the highest calcium oxalate crystal-cell adhesion occurs at the most acidic pH.S4
Oral citrate therapy increases the excretion of urinary citrate, which binds to calcium, and inhibits its crystallization; thus, prevents kidney stone recurrence.S5 Citric also increases urinary pH. However, our previous study did not examine the effect of SGLT2 inhibition on urinary citrate excretion.4 Another limitation of our epidemiologic study is the lack of urinary pH data.1 Our previous in vivo and in vitro studies showed that SGLT2 inhibitors prevent renal stone formation because of their anti-inflammatory and anti-fibrotic effects, and potentially elevate urinary pH in rats with renal calcium oxalate stone formation.4 Clinical trials to determine the effects of SGLT2 inhibitors in urolithiasis patients are needed.
Footnotes
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Supplementary Material
Supplementary References.
References
- 1.Anan G., Hirose T., Kikuchi D., et al. Impact of sodium-glucose cotransporter-2 inhibitors on urolithiasis. Kidney Int Rep. 2023;8:925–928. doi: 10.1016/j.ekir.2023.01.034. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2.Harmacek D., Bonny O. Sodium/glucose cotransporter 2 inhibition and urolithiasis: the effect of urinary pH and citrate. Kidney Int Rep. 2023;8:1268. doi: 10.1016/j.ekir.2023.02.1094. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3.Maalouf N.M., Sakhaee K., Parks J.H., Coe F.L., Adams-Huet B., Pak C.Y. Association of urinary pH with body weight in nephrolithiasis. Kidney Int. 2004;65:1422–1425. doi: 10.1111/j.1523-1755.2004.00522.x. [DOI] [PubMed] [Google Scholar]
- 4.Anan G., Hirose T., Kikuchi D., et al. Inhibition of sodium-glucose cotransporter 2 suppresses renal stone formation. Pharmacol Res. 2022;186:106524. doi: 10.1016/j.phrs.2022.106524. [DOI] [PubMed] [Google Scholar]
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