Stopping the groans from recurrent stones

Randeep is currently rolling around in agony on your examination couch. He has renal colic. You’ve already jabbed him with IM diclofenac and are wishing the practice still kept morphine. You’ve already called 999 and wishing the ambulance service didn’t de-prioritise him because you’re a doctor and he’s in a “place of safety”. As you hopefully wait for the NSAID to kick in your brain reminds you that prevention is better than a cure. 

This isn’t Randeep’s first renal stone, he’s had many. He’s not alone. The incidence of kidney stones in the UK is on the rise with a lifetime risk of between 10 and 15% (BJGP 2020). Up to half will have a recurrent episode within 10 years and for some this will be a frequent problem with short-term risks and long-term complications. 

New research, published in the BMJ (2024;387:e080035), highlights that as well as all the myriad of benefits currently discovered for SGLT2 inhibitors, they may also have a role in the prevention of recurrent renal stones.

The researchers examined 20k patients with nephrolithiasis (kidney stones) and type 2 diabetes, identified on a Canadian population database, and compared rates of renal stone episodes in those initiated on SGLT2 inhibitors, GLP1 receptor agonists or DPP-4 inhibitors, with the latter two acting as control groups.

The results showed that use of an SGLT2 inhibitor resulted in a lower rate of recurrent kidney stone events by around a third, 105 per 1000 person years, compared to those on GLP1ra, at 156 per 1000 person years (possibly identifying the only condition the injections don’t appear to help with…).

To put that in more helpful figures, there was a numbers needed to treat (NNT) of 20 to prevent one episode of recurrent nephrolithiasis, which is pretty reasonable, but is much better much better in people with recently active kidney stones with an NNT = 5.

The linked editorial explains the mechanism by which SGLT2i may prevent renal stones is not entirely clear. It may be linked to osmotic diuresis and the subsequent dilution of urine, or increased excretion of urinary citrate, or an anti-inflammatory effect as inflammation has been suggested to facilitate stone formation. 

Regardless, this positive finding adds to the body of evidence supporting the use of SLGT2i to prevent recurrent renal stones. But there are caveats, principally that these studies have only examined patients with type 2 diabetes, partly because T2DM is an independent risk factor for renal stones, but also because this population can be easily studied as patients can legitimately and often are prescribed SGLT2i. 

So what can we do to help Randeep? 

If he has type 2 diabetes and he isn’t already on an SGLT2 inhibitor, this data makes a compelling argument for starting treatment. 

If he does not have T2DM then we currently don’t know if these drugs will help. However, there are a number of alternatives which may be of benefit. NICE NG118 published in 2019, advising a number of interventions for recurrent kidney stones:

• Dietary measures include drinking between 2.5 and 3L of water per day for adults, adding fresh lemon juice to water, avoiding carbonated drinks and limiting salt intake to 6g per day, and generally maintaining a healthy lifestyle. 
• Check the type of stone if you can (make sure they wash the sieve well afterwards…). 
  • For stones formed of predominantly calcium oxalate consider potassium citrate off label (granules in sachets or effervescent tablets are more palatable that syrup which is apparently disgusting). 
  • Low calcium diets are not helpful or appropriate – calcium levels are not the driver of renal stone formation.
  • Specialist renal guidelines have recommendations for other types of stone and referral is entirely appropriate for people with recurrent renal stones if this hasn’t happened after their inevitable hospital excursions.

Meanwhile, Randeep’s pain is easing off and it’s time to see the next patient. Sounds like recurrent gout. As the same BMJ paper found, SGLT2 inhibitors may help with gout too, but that’s for another blog.