Research In Practice Blog
A recent multi-institutional randomized controlled trial conducted by researchers at the Children's Hospital of Philadelphia (CHOP) examined an innovative behavioral program aimed at increasing fluid intake and reducing the risk of recurrent kidney stones in patients with urinary stone disease (USD) and low urine volume. The trial utilized various tools, including a smart water bottle, personalized hydration goals, financial incentives, and coaching to help participants maintain high fluid intake. The study found that, while the program led to a modest increase in urine output, it did not lower the recurrence rates of symptomatic kidney stones. These findings were recently published in the journal The Lancet, paving the way for future research and improvements in kidney stone prevention strategies.
CHOP served as one of the clinical centers for the trial, led by CHOP pediatric urologist Gregory Tasian, MD, MSc, MSCE and co-senior author of the Prevention of Urinary Stones with Hydration (PUSH) trial. Dr. Tasian is Professor of Surgery and Epidemiology, director for the Center for Outcomes Research in Surgery (CORES), and Co-Associate Director for Clinical Trials at Clinical Futures, a CHOP Research Institute Center of Emphasis. He is also Director of the PKIDS Care Improvement Network, an attending pediatric urologist in the Division of Urology . For years, Dr. Tasian has been leading efforts at CHOP to improve the health of children and adolescents with early-onset kidney stone disease through randomized trials, prospective observational studies, and large data analytics. The PUSH trial is the largest health behavior intervention trial ever conducted for the prevention of kidney stones and one of few randomized trials that included adolescents with kidney stones.
Trial Methodology
The PUSH trial enrolled 1,658 adolescents and adults across six U.S. academic centers, including CHOP, between 2017 and 2024. The trial focused on a health behavior approach aimed at maintaining high fluid intake, specifically, how consistently individuals consume adequate fluids, such as water or lemonade. This study involved participants aged 12 and older who had urinary stone disease and low urine volume. The PUSH intervention was designed based on behavior-change principles to help individuals overcome common barriers to consistently following recommendations to maintain high fluid intake to reduce kidney stone recurrence. Participants in the intervention group received a Bluetooth-enabled smart water bottle that measured and recorded their fluid intake. They also received financial incentives to encourage them to meet a personalized hydration goal, known as a “fluid prescription.” The “fluid prescription” for increasing fluid intake was determined by comparing each participant’s typical urine output with the additional amount of water they needed to drink to achieve a urine output goal of at least 2.5 liters (approximately 10.5 cups) per day, as recommended in clinical guidelines, or an equivalent amount for younger adolescents. Additionally, adaptive health coaching helped participants identify and overcome obstacles to reaching their fluid intake goals, along with supportive measures, such as text message reminders.
In contrast, participants in the control group received a smart water bottle to use at their discretion (without a specific fluid prescription) and received standard care according to clinical guidelines.
The main outcomes of the PUSH trial are as follows:
Primary Outcome
- At a median follow-up of 738 days (with a range of 711 to 778 days), 154 participants (18.6%) in the intervention group experienced a symptomatic stone event, compared to 165 participants (19.8%) in the control group, resulting in a hazard ratio (HR) of 0.96 (95% confidence interval [CI] 0.77 to 1.20). There was no significant difference in the cumulative risk of symptomatic stone recurrence between the two groups. Subgroup analyses indicated no variation in treatment effects based on sex, age, clinical center, or provider.
- Additionally, adherence to the intervention, defined as completing at least two 24-hour urine collections that met or exceeded the target of 2.5 liters per day for adults, was consistent across adherence subgroups. Sensitivity analyses, which excluded participants who underwent surgery for asymptomatic stones and stone events occurring within 30, 60, and 90 days post-randomization, also showed no differences between the groups. A hierarchical order (win-ratio) analysis further confirmed no differences between treatment groups.
Secondary Outcome
- The 24-hour urine volume increased from baseline in both groups and was found to be higher in the intervention group at six, twelve, eighteen, and twenty-four months compared to the control group. Urinary storage symptoms, including frequency, urgency, and nocturia, were more pronounced in the intervention group than in the control group at six months (p=0.050) and twelve months (p=0.014), but not at other time points.
- There was no significant difference in stone growth of ≥2 mm (odds ratio [OR] 1.44; 95% CI 0.91 to 2.29) or in the formation of new stones (OR 0.99; 95% CI 0.72 to 1.37) between the groups from baseline to end-of-study imaging. The composite outcome of symptomatic stone recurrence, new stone formation, or stone growth was also not statistically different between the treatment groups.
Clinical Implications
As in previous trials, researchers observed that female participants were more affected than male participants in this study, a trend that aligns with existing patterns in urinary stone disease. Dr. Tasian noted, “Over the last 20 years, the demographic distribution of kidney stones has changed dramatically, particularly among adolescents and young adults. There is now a predominance of females affected, with more girls and young women experiencing kidney stones than boys and their male counterparts. Among adults, the distribution is closer to 1:1, with approximately 55% male and 45% female.”
One possible reason for the higher number of female participants in the PUSH trial could be that women are generally more likely to participate in behavioral intervention trials. The predominance of female participants may indicate gender differences in willingness to engage in clinical research. While this is a possibility for this study, researchers believe it should not significantly impact the results.
Although there was no difference in stone recurrence between the groups, this trial carries important implications for behavioral science and stone prevention efforts. The intervention increased urine volume but did not reduce the long-term clinical goal of preventing stone recurrence. The results of the PUSH study do not undermine the importance of increasing fluid intake for stone prevention, as this remains a low-cost, low-risk intervention with likely benefits, supported by prior literature. Instead, the study suggests that while the contingency management intervention, coupled with health coaching for non-adherent participants, did not yield significant clinical benefits compared to control participants, future studies could employ optimization study designs (e.g., factorial designs or sequential, multiple assignment, randomized trial designs) within a multi-phase optimization strategy (MOST) framework to identify strategies that yield the best results for the majority of people.
Additional qualitative research may provide important insights into patient barriers to fluid intake, which could inform the design of future interventions. A more personalized medicine approach might be adopted to address individual differences in motivation to consume water, thereby helping to prevent recurrent kidney stones.
Partners and Collaborators
The research was conducted by the Urinary Stone Disease Research Network, coordinated by the Duke Clinical Research Institute (DCRI), and funded by the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health. This study builds upon years of patient-centered research conducted by Dr. Tasian. The Urinary Stone Disease Research Network will ensure that patients and caregivers remain at the center of the trial and are involved in key decisions. All participating sites share a common data model for electronic health record (EHR) data. Along with CHOP, University of Pennsylvania, University of Texas Southwestern Medical Center, University of Washington, and Washinton University, served as the clinical coordination centers participating sites include Cleveland Clinic Foundation, Mayo Clinic Foundation, Duke Clinical Research Institute and the National Institute of Diabetes and Digestive and Kidney Disease (NIDDK).
For more information, read this CHOP News Brief and this Cornerstone Blog post from the CHOP Research Institute.
This study was supported by the National Institute of Diabetes and Digestive and Kidney Diseases grants DK110986, DK110961, DK110954, DK110994 DK110988.