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Although good evidence now suggests that SGLT-2 inhibitors may help prevent recurrent formation of kidney stones, the underlying mechanisms have not been fully explored. Several mechanisms are possibilities. First, osmotic diuresis and dilution of urine would reduce the urinary super saturation that underlies urinary crystallization of stone-forming salts. Second, increased urinary citrate excretion—as shown previously in healthy volunteers treated with empagliflozin compared with placebo—may have a beneficial effect in patients with calcium related nephrolithiasis.9 Finally, the protective effect against kidney stones could be explained by the anti-inflammatory actions of SGLT-2 inhibitors influencing the balance between pro-inflammatory and anti-inflammatory cytokines that could facilitate kidney stone formation.10 To answer these questions, a short term proof of concept study followed by long term prospective clinical trials would be of value to patients, clinicians, and researchers. These studies could explore the underlying metabolic factors influencing the formation of kidney stones and inform the development of more targeted treatments. Future studies should also recruit patients with nephrolithiasis but no concurrent diabetes to test whether SGLT-2 inhibitors could be beneficial for them.

ers. These studies could explore the underlying metabolic factors influencing the formation of kidney stones and inform the development of more targeted treatments. Future studies should also recruit patients with nephrolithiasis but no concurrent diabetes to test whether SGLT-2 inhibitors could be beneficial for them. A recent trial of hydrochlorothiazide, a commonly used treatment for hypercalciuric nephrolithiasis, failed to show its hypothesized effect in reducing the formation of kidney stones.11 However, one reason to consider SGLT-2 inhibitors instead of hydrochlorothiazide for patients prone to kidney stones is that new onset diabetes and gout were both more common among trial participants receiving hydrochlorothiazide compared with placebo. McCormick and colleagues’ study strengthens the evidence supporting use of SGLT-2 inhibitors for patients with recurrent nephrolithiasis, type 2 diabetes, and comorbidities such as gout. Further research to identify underlying mechanisms of action, and to evaluate use for patients without type 2 diabetes, would help strengthen the evidence still further.