Add on SGLT-2 Inhibitors may help manage recurrence of nephrolithiasis and Gout in kidney stone patients, suggests study

"In a study involving over 20,000 patients with type 2 diabetes and nephrolithiasis, those who began treatment with SGLT-2 inhibitors had significantly fewer recurrent kidney stone events than those using GLP-1 receptor agonists or DPP-4 inhibitors. This protective benefit was especially evident in patients with active nephrolithiasis who also had gout. Additionally, SGLT-2 inhibitors were linked to a reduction in gout flare-ups," the researchers reported.

Nephrolithiasis, commonly known as kidney stones, is a painful condition that can lead to significant morbidity. Patients with a history of kidney stones often find themselves in a cycle of recurrence, which can be exacerbated by conditions such as gout. Traditionally, treatment options for managing nephrolithiasis have been limited, focusing mainly on lifestyle modifications and pain management.

Against the above background, Natalie McCormick, Department of Medicine, Harvard Medical School, Boston, MA, USA, and colleagues conducted target trial emulations to compare the recurrence of nephrolithiasis in patients with a history of nephrolithiasis—both overall and specifically for those with concurrent gout—who start treatment with SGLT-2 inhibitors versus an active comparator.

The researchers conducted target trial emulation studies using a Canadian population database from 2014 to 2022, analyzing data from 20,146 patients with nephrolithiasis and type 2 diabetes, including those with gout. They compared the initiation of SGLT-2 inhibitors and GLP-1 receptor agonists against DPP-4 inhibitors. The primary outcome was recurrent nephrolithiasis events identified through emergency department visits and hospital admissions. Secondary outcomes included nephrolithiasis-related admissions and gout flare-ups. Data analysis utilized Poisson and Cox proportional hazards regression models to evaluate the effectiveness of SGLT-2 inhibitors in preventing kidney stones in high-risk patients.

The study led to the following findings:

• After adjusting for treatment effects, there were 1,924 recurrent nephrolithiasis events among 14,456 patients using SGLT-2 inhibitors (105.3 events per 1,000 person-years), compared to 853 events among 5,877 patients on GLP-1 receptor agonists (156.4 events per 1,000 person-years).
• The adjusted rate ratio was 0.67, indicating a rate difference of -51 events per 1,000 person-years (NNT of 20).
• For patients with recently active nephrolithiasis, the absolute rate difference was 219 events per 1,000 person-years (NNT of 5).
• The protective effect of SGLT-2 inhibitors persisted for nephrolithiasis events requiring emergency department visits or hospital admissions, with a rate ratio of 0.73 and a rate difference of -38 per 1,000 person-years (NNT of 26).
• Among patients with nephrolithiasis and gout, the rate ratio versus GLP-1 receptor agonists was 0.67 with a rate difference of -53 per 1,000 person-years (NNT of 19), and versus DPP-4 inhibitors, the rate ratio was 0.63 with a rate difference of -62 per 1,000 person-years (NNT of 16).
• SGLT-2 inhibitors were associated with fewer gout flare-ups, showing a rate ratio of 0.72 and a rate difference of -16 per 1,000 person-years compared to GLP-1 receptor agonists.
• SGLT-2 inhibitor users had a higher risk of genital infections (hazard ratio 2.2) and did not show a changed risk for osteoarthritis or appendicitis.
• Results remained consistent with propensity score overlap weighting.

"The findings from these target trial emulations indicate that SGLT-2 inhibitors could be a valuable addition to existing treatments for patients with nephrolithiasis, helping to manage both the recurrence of kidney stones and related comorbidities, such as gout," the researchers concluded.

Reference:

McCormick N, Yokose C, Lu N, Wexler D J, Aviña-Zubieta J A, De Vera M A et al. Comparative effectiveness of sodium-glucose cotransporter-2 inhibitors for recurrent nephrolithiasis among patients with pre-existing nephrolithiasis or gout: target trial emulation studies BMJ 2024; 387:e080035 doi:10.1136/bmj-2024-080035