A behavioral intervention designed to increase fluid intake for the prevention of kidney stone recurrence successfully boosted urine volume but did not significantly reduce stone recurrence over 2 years, according to results from the largest randomized controlled trial of its kind.

“The trial results show that despite the importance of high fluid intake to prevent stone recurrence, achieving and maintaining very high fluid intake is more challenging than we often assume for people with urinary stone disease,” co-senior author Charles D. Scales Jr, MD, associate professor of urology and population health sciences at Duke University School of Medicine, Durham, North Carolina, said in a press statement. The study was published on March 21 in The Lancet.

Guidelines from the American Urological Association and the European Association of Urology recommend fluid intake of at least 2.5 L/d to prevent of kidney stone disease. However, evidence supporting the advice is limited. A 2020 Cochrane review identified only a single randomized controlled trial on the subject, resulting in low-certainty evidence designation.

Findings From the PUSH Trial

To address this gap, Scales and colleagues conducted the PUSH trial, enrolling 1658 participants (median age, 44 years; 57% women) aged 12 years or older with a history of urinary stone disease and low 24-hour urine volumes. Participants were recruited from six US medical centers between October 2018 and February 2022.

Participants were randomized to either a multi-component behavioral intervention (n = 826) or usual care (n = 826). The intervention included a prescribed fluid intake goal, financial incentives to encourage adherence, health coaching to overcome hindrances, and patient-suggested strategies such as text message reminders. The control group received conventional guideline-recommended care. Treating physicians and outcome assessors were blinded to participants’ group assignment.

At a median follow-up of 738 days, the primary outcome of symptomatic kidney stones occurred in 154 participants (19%) in the intervention group and 165 (20%) in the control group, a nonsignificant difference (hazard ratio, 0.96). Overall, 66.6% of participants had recurring kidney stones.

There were also no differences in a composite outcome of symptomatic stone recurrence, new stone formation, or stone growth of at least 2 mm.

Both groups had increases in 24-hour urine volume from baseline. At 6 months, the intervention group had a greater increase (600 mL vs 360 mL per 24 hours in the control group), but this difference diminished over time.

Although no cases of hyponatremia requiring hospitalization were reported, asymptomatic hyponatremia occurred in 12 participants (1%) in the intervention group and two (< 1%) in the control group.

“To the best of our knowledge, the PUSH trial is the largest randomized controlled trial designed to improve adherence to fluid intake for secondary prevention of urinary stones to date,” the authors noted.

Scales suggested that a key reason for the lack of benefit could be that neither group achieved the guideline-recommended urine output of 2.5 L/d.

“The average urine output in both the intervention and control group did not meet this threshold, even though the intervention group made more urine than the control group throughout the study,” Scales told Medscape Medical News.

Nevertheless, the increased urine output indicates that “the behavioral intervention did work to increase fluid consumption in the intervention group,” he added. Among patients with high adherence to the intervention, stone prevention was slightly better, although not statistically significant.

The results should therefore not be interpreted as suggesting that higher fluid intake does not prevent kidney stone recurrence, Scale said. Instead, prevention strategies may need to be more individualized.

“Clinicians and patients should understand that drinking large amounts of water consistently can be difficult for many people, and it is important to personalize prevention strategies for individuals,” Scales explained.

For example, he noted that for individuals such as rideshare drivers, practical barriers such as access to water and restroom availability can make adherence challenging.

“Clinicians need to understand patients’ lives and personalize hydration and other prevention strategies in a realistic, achievable way,” he said.

Broader Evidence Suggests Modest Benefit — With Caveats

A separate systematic review published in March in the Annals of Internal Medicine found some evidence supporting strategies to prevent kidney stone formation and recurrences, though with important limitations.

“We found a variety of interventions that appear to have some effect, but our confidence in the magnitude of those effects remains low, due in large part to the paucity of studies for most interventions we looked at, as well as the risk of bias in many of those studies,” first authorGary N. Asher, MD, MPH, of the University of North Carolina at Chapel Hill, told Medscape Medical News.

The review included 31 studies but, like the earlier Cochran Asher review, identified only one previous randomized controlled trial evaluating hydration.

Other interventions showing at least modest benefit included diets with normal to high calcium, low protein, and low sodium, as well as thiazide diuretics, alkali therapy, and allopurinol for calcium-based stones.

However, the authors concluded that “it is largely uncertain whether other pharmacologic or dietary interventions prevent recurrent symptomatic stones.”

Given the limited evidence base, Asher noted that “additional studies might meaningfully change our estimate of effect, which could be in either direction.”

Regarding the PUSH trial (which was not included in the review), Asher said the findings do not warrant changing clinical recommendations.

“Increasing fluid intake is safe, inexpensive, and may yet still be beneficial, but the interventions in this trial were unsuccessful [in preventing kidney stone recurrence],” he said.

“I wouldn’t yet change my recommendations for fluid intake based on this study alone.”

The Lancet study was funded by the National Institute of Diabetes and Digestive and Kidney Diseases. The systematic review was funded by the Patient-Centered Outcomes Research Institute and Agency for Healthcare Research and Quality. Scales reported participating on a Data Safety Reporting Board of the University of Michigan PCORI-funded study. Asher has disclosed no relevant financial relationships. Full author disclosures are available in the original publications.