Pass on Kidney Stone Meds, Study Suggests

Pam Harrison

March 23, 2018

COPENHAGEN — Medical expulsive therapy, which is routinely used to hasten the passage of ureteral or kidney stones in patients experiencing acute ureteric colic, has no effect on spontaneous stone passage and is essentially a waste of time and money, results from the MIMIC study show.

There was no benefit, "regardless of stone size or position in the ureter, so we're concluding that these medications should not be routinely prescribed," said Taimur Shah, MBBS, vice-chair of British Urology Researchers in Surgical Training (BURST), a research collaborative developed and led by residents in the United Kingdom.

"We know that a lot of stones smaller than 10 mm, and particularly those smaller than 5 mm, will pass naturally, without us needing to intervene surgically," said Shah. On average, it takes about a month to pass a kidney stone, depending on its size.

"It was felt that medications like alpha blockers and calcium-channel blockers helped stone passage, but at the time we were developing this study, we were finding that the data were quite mixed," he told Medscape Medical News.

Neither alpha blockers nor calcium-channel blockers showed any benefit in the large SUSPEND trial (Health Technol Assess. 2015;19:vii-viii, 1-171), but alpha blockers were shown to be beneficial in a large systematic review and meta-analysis (BMJ. 2016;355:i6112).

Shah presented results from MIMIC — a multicenter, international cohort study conducted at 71 centers by the BURST Collaborative MIMIC Study Group — during a poster session here at the European Association of Urology 2018 Congress.

The team assessed whether medical expulsive therapy improved rates of spontaneous stone passage in 2516 conservatively managed patients, most of whom received tamsulosin, an alpha blocker marketed (in part) as a facilitator of the passage of kidney stones.

There was no association between expulsion therapy and spontaneous stone passage in any subgroup after adjustment for age, sex, stone size, or stone position in the ureter.

Overall, the odds ratio for the acceleration of stone passage with medical expulsive therapy was 0.86 (95% confidence interval, 0.52 - 1.40). But regardless of which variable the researchers assessed, the odds ratio was largely neutral.

Table. Odds Ratio of Spontaneous Stone Passage

Variable Odds Ratio
Expulsive therapy 0.861
Stone size (mm) 0.714
Stone in the middle ureter  
Expulsive therapy 0.808
No expulsive therapy 0.806
Stone in the upper ureter  
Expulsive therapy 1.086
No expulsive therapy 0.435


Medical Expulsive Therapy and Pain

The team did not assess the effect that either alpha blockers or calcium-channel blockers had on pain in patients passing a kidney stone.

"Classically, we've used nonsteroidal antiinflammatory drugs to treat kidney stone pain, which can be given either rectally or orally," said Shah.

"Patients with renal colic tend to have pain that comes in waves. Conservative management is really for patients who can tolerate the pain, when it spikes, with adequate oral analgesia," he reported.

But for patients in severe pain all the time, "we would not carry on managing these patients conservatively," he explained. "We'd need to intervene."

In some places, like the United Kingdom, patients with acute ureteric colic tend to be managed with a retrograde stent, inserted during cystoscopy, provided they are not septic.

For many patients, there is no known cause for kidney stones. However, to reduce the risk of developing stones, "fluid intake is probably one of the biggest factors in stone formation," Shah said. "I tell patients to drink at least 2 liters of water a day and to aim to keep their urine colorless."

When people say we shouldn't be prescribing these drugs, I would caution them not to throw the baby out with the bathwater.

This is an observational study, so it is important that people not make causal inferences, said John Hollingsworth, MD, from the University of Michigan in Ann Arbor.

In their systematic review and meta-analysis of more than 50 trials (BMJ. 2016;355:i6112), the benefit of alpha blockers shown by Hollingsworth and his colleagues was seen primarily in patients with ureteral stones 5 mm or larger.

"That finding is not inconsistent with what has been published in the literature," Hollingsworth told Medscape Medical News.

A recent Chinese study supports the use of tamsulosin, but, again, only in patients with larger stones; no benefit was seen in patients with stones 5 mm and smaller (Eur Urol. 2018;73:385-391), he noted.

"My general take on the literature, when we look at all the studies, including our own, is that there appears to be a benefit from medical expulsion therapy. So when people say we shouldn't be prescribing these drugs, I would caution them not to throw the baby out with the bathwater," Hollingsworth said.

"And while I don't believe there is a benefit for patients with smaller stones, I think there is a subset of the population that presents to the emergency department that could benefit," he said.

Shah has disclosed no relevant financial relationships. Hollingsworth reports receiving grant funding from the Agency for Healthcare Research and Quality and Blue Cross Blue Shield of Michigan.

European Association of Urology (EAU) 2018 Congress: Abstract 637. Presented March 18, 2018.

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