A behavioral intervention to maintain high fluid intake in individuals with a history of urinary stone disease modestly increased urinary output but did not reduce recurrent stone events, according to new research presented at the 2025 annual meeting of the American Urological Association.
“Multicomponent interventions did result in significant behavioral change and improve surrogate outcomes of increased urinary output, but failed to achieve the desired clinical effect,” said study author Alana Desai, MD, a clinical associate professor in the Department of Urology at the University of Washington, who presented the findings during a plenary session. “This highlights the importance of evaluating the effects of interventions on meaningful clinical endpoints in adherence trials rather than surrogate outcomes.”
Increased fluid intake is universally recommended to decrease the risk of recurrent urinary stones, but adherence to these recommendations is challenging. The effectiveness of interventions to encourage at-risk individuals to maintain high fluid intake to reduce stone recurrence has not been well studied.
“We hypothesized that a program of behavioral interventions to increase fluid intake will reduce the risk of stone disease recurrence in stone forming patients with a low urine volume, as compared to usual care,” said Dr. Desai.
To test their hypothesis, Dr. Desai and colleagues initiated the multicenter randomized controlled Prevention of Urinary Stones with Hydration (PUSH) clinical trial. The cohort included 1658 participants aged 12 years and older, who had a history of urinary stone disease and low 24-hour urine volume, and who were assigned to either: a multi-component behavioral intervention program to maintain high fluid intake, or usual care including high fluid intake recommendations.
The study’s primary end point was symptomatic recurrence of stones, that was defined as passage of a stone or the need for procedural intervention for stone(s) during a 2-year follow-up period. This endpoint was evaluated according to the intent-to-treat principle and analyzed as time-to-event by treatment group with a log-rank test.
Secondary endpoints included assessing urine output at 6-, 12-, 18-, and 24-month time points, the formation of new stones observed on imaging at 24 months, growth of existing stones by ≥2 mm at 24 months, and a composite outcome comprised of symptomatic stone recurrence, new stone formation, or stone growth.
Participants also had 24-hour urine volume measurements done at baseline, 6, 12, 18, and 24 months, which were analyzed using a repeated-measures mixed-effects model. Urinary symptoms in adults were assessed at intervals beginning at baseline and then at 6, 12, 18, and 24 months. Hyponatremia that required hospitalization was the pre-specified safety end point.
Median follow-up was 24 months, and at that time, 319 (19.2%) participants experienced a primary outcome event. A total of 154 (18.6%) of patients in the intervention arm experienced a stone event as compared to 165 (19.8%) in the control arm. The Kaplan Meier rate at 2 years was 19.6% vs 21.1%, respectively.
“For the secondary outcome, there was a significant increase in urine output in the intervention arm at all time points, with the difference decreasing over time but still remaining significant at 24 months,” said Dr. Desai. “On imaging, there was no difference in asymptomatic stone formation or stone growth or any difference in the composite outcome between groups.”
None of the participants experienced hyponatremia requiring hospitalization, but 291 (17.6%) participants discontinued the study prior to 24-month follow-up.
“PUSH is a high quality trial and the largest stone prevention trail with the target enrollment and primary outcome events exceeding projections, although attrition rate was lower than expected,” said Dr. Desai. “The intervention resulted in increased urine output compared to control arm but neither arm achieved average volumes at or above guidelines, and there was no difference in our primary endpoint of symptomatic stone recurrence or secondary stone related outcomes.”
The study was funded by the National Institutes of Health/ National Institute of Diabetes and Digestive and Kidney Diseases
Dr Desai has no relevant disclosures
P2s: Practice-changing, Paradigm-shifting Clinical Trials in Urology: Prevention of Urinary Stones with Hydration: A Randomized Clinical Trial. Presented April 27, 2025 at the 2025 Annual Meeting of the American Urological Association
Image by BRO Vector / GettyImages
