Prevention of urinary stones with hydration: a randomised clinical trial of an

# Prevention of urinary stones with hydration: a randomised clinical trial of an adherence intervention *The Lancet 2026* Articles Prevention of urinary stones with hydration: a randomised clinical trial of an adherence intervention Alana C Desai*, Naim M Maalouf†, Jonathan D Harper†, Sri Sivalingam, John C Lieske, H Henry Lai*, Peter P Reese, Hunter Wessells, Hongqiu Yang, Hussein R Al-Khalidi, Ziya Kirkali, Gregory E Tasian‡, Charles D Scales Jr‡ for the Urinary Stone Disease Network Investigators Summary Background Increased fluid intake is universally recommended to decrease the risk of recurrent urinary stones; Lancet 2026; 407: 1171–81 however, adherence is challenging. The eectiveness of interventions to maintain high fluid intake has not been well See Comment page 1123 studied. We sought to determine whether a multicomponent behavioural intervention programme to promote high *Equal contributions at fluid intake reduces symptomatic stone recurrence, compared with a control. Washington University in St Louis, St Louis, MO, USA Methods In this randomised clinical trial, participants aged 12 years and older with a history of urinary stone disease †Equal number of participants randomised at University of and low 24 h urine volumes based on current guidelines were enrolled at six academic medical centres in the USA. Texas Southwestern Medical Participants were randomly assigned in a 1:1 ratio to a multicomponent behavioural intervention designed to promote Center Dallas, TX, USA, and increased fluid intake or to the control group receiving guideline-concordant care. The intervention consisted of a University of Washington, fluid prescription, financial incentives to adhere to fluid prescription, health coaching to overcome barriers to Seattle, WA, USA consuming more fluids, and patient-selected approaches such as text messaging to maintain increased fluid intake. ‡Contributed equally Randomisation assignment was computer-generated remotely, and investigators, treating physicians, outcome Department of Surgery, assessors, and adjudicators were masked to group assignment. The primary outcome was symptomatic stone Division of Urology (A C Desai MD, Prof H H Lai MD), recurrence defined as stone passage or procedural intervention for stone(s) during a 2-year follow-up period, analysed Department of Anesthesiology in the intention-to-treat population. Secondary outcomes included change in 24 h urine volume, urinary symptoms, (Prof H H Lai), Washington radiographic stone recurrence or growth, and a composite outcome of symptomatic stone recurrence, new stone University in St Louis, St Louis, MO, USA; Department of formation, and growth of existing stone(s); hyponatremia requiring hospitalisation was the safety endpoint. This trial Internal Medicine and Charles & is registered with ClinicalTrials.gov, NCT03244189. Jane Pak Center for Mineral Metabolism and Clinical Findings Between Oct 26, 2017, and Feb 18, 2022, 1658 participants were randomly assigned to intervention (n=826) Research, University of Texas Southwestern Medical Center, and control (n=832) groups (median age 44 years [IQR 29–59]; 946 [57%] female). At a median follow-up of 738 days Dallas, TX, USA (IQR 711–778), symptomatic stone events occurred in 154 (19%) participants in the intervention group and 165 (20%) in (Prof N M Maalouf MD); the control group (hazard ratio 0·96, 95% CI 0·77–1·20). Among these 1658 participants, 1104 (66·6%) were recurrent Department of Urology, stone formers. 24 h urine volume increased from baseline in both groups and was higher in the intervention group University of Washington School of Medicine, Seattle, at months 6, 12, 18, and 24 compared with the control group. Urinary storage symptoms of frequency, urgency, and WA, USA (Prof J D Harper MD, nocturia were greater in the intervention group versus control at months 6 and 12 but not at other timepoints. There Prof H Wessells MD); Glickman was no dierence in stone growth of at least 2 mm or new stones between groups from baseline to end-of-study Urological & Kidney Institute, imaging, and the composite outcome of symptomatic stone recurrence, new stone formation, or stone growth of at Cleveland Clinic Foundation, Cleveland, OH, USA least 2 mm was also not statistically dierent between groups. No episodes of hyponatremia requiring hospitalisation (S Sivalingam MD); Department (safety endpoint) were reported; 12 (1%) participants in the intervention group had asymptomatic hyponatraemia of Nephrology and versus two (<1%) participants in the control group. Hypertension, Mayo Clinic Foundation, Rochester, MN, USA (Prof J C Lieske MD); Interpretation A behavioural intervention programme to promote fluid intake for secondary stone prevention did not Division of Renal Electrolyte reduce recurrent stone events but modestly increased urine volume compared with guideline-based care during a and Hypertension, Department 2-year follow-up period. of Medicine, Perlman School of Medicine, University of Pennsylvania School of Funding National Institute of Diabetes and Digestive and Kidney Diseases. Medicine, Philadelphia, PA, USA (Prof P P Reese MD); Duke Copyright © 2026 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar Clinical Research Institute technologies. (H Yang PhD, Prof H R Al-Khalidi PhD, C D Scales Jr MD), Department Introduction reduced urinary stone recurrence, rated as low-certainty of Biostatistics & Urinary stone disease is a common disorder of mineral evidence. This seminal trial by Borghi and colleagues,7 Bioinformatics metabolism marked by episodic painful events1 that comparing high fluid intake versus no additional fluid (Prof H R Al-Khalidi), Departments of Urology and negatively aect physical, social, and emotional health.2 intake in 199 participants, demonstrated benefit for Population Health Science Guideline-based prevention strategies emphasise high increased hydration. Thus, achieving and maintaining (C D Scales Jr), Duke University fluid intake as a cornerstone of reducing recurrence high fluid intake could provide safe and eective School of Medicine, Durham, risk.3–5 A Cochrane review6 included a single randomised secondary prevention of symptomatic urinary stones. NC, USA; National Institute of Diabetes and Digestive and controlled trial that showed increased water intake However, maintaining high fluid intake is a formidable Articles Kidney Diseases, Bethesda, MD, Research in context USA (Prof Z Kirkali MD); Children’s Hospital of Evidence before this study trials identified only via ClinicalTrials.gov compared a Philadelphia, Philadelphia, PA, USA (Prof G E Tasian MD) We performed a systematic search of PubMed for randomised smartphone application delivering prevention education versus Correspondence to: trials testing interventions to promote adherence to fluid intake a control group receiving no stone prevention information. Dr Charles D Scales, Departments for secondary prevention of urinary stone disease. We searched The sixth trial (comparing the mobile app care plan versus the of Urology and Population PubMed (from Jan 1, 1995, to June 2, 2025); the detailed search standard kidney stone follow-up pathway) was identified only Health Sciences, Duke University strategy is available in the appendix (p 4). We also searched via a conference abstract; no ClinicalTrials.gov registration was School of Medicine, Durham, NC 27710, USA ClinicalTrials.gov (from inception to June 2, 2025) to identify identified. Current guidance for water intake for secondary chuck.scales@duke.edu similar trials in progress or without published results. stone prevention is based on a Cochrane Systematic See Online for appendix We identified 222 publications and five ClinicalTrials.gov listings. Review (2020) that found a single randomised controlled trail Of these, we identified six trials (including one published only as a (Borghi, 1996) comparing the effects of high water intake conference abstract) testing adherence interventions for fluid versus low water intake for secondary urinary stone disease intake for secondary stone prevention. Of these six trials, two were prevention. Cochrane assessed this randomised controlled trial initiated before 2017, when our Prevention of Urinary Stones with as low-certainty evidence. Hydration (PUSH) trial began. The Hidrate Me study Added value of this study (NCT02938884) randomly assigned participants with a history of The PUSH trial advances the field by testing an adaptive, urinary stone disease and low urine volume to a smart water multicomponent behavioural health approach to promoting bottle (Hidrate Spark) versus standard water bottle, facilitating fluid intake adherence in a large population of patients with self-monitoring of behaviour in the intervention group. urinary stone disease and low urine volume. The PUSH The results of this trial were reported in 2022. Among intervention is grounded in contingency management, 85 participants enrolled, 51 (60%) completed 24 h urine leveraging a loss-framed financial incentive, along with an collections at 6 weeks, with a greater mean increase in urine adaptive structured problem-solving intervention that is volume over baseline in the smart water bottle group than in the responsive to participant non-adherence. In addition to control group (+1·37 [SD 0·94] L per day vs +0·79 [SD 0·97] L examining 24 h urine output, PUSH is the first adherence study per day, p=0·04). Stone recurrence was not ascertained as an to assess the clinical endpoint of urinary stone recurrence. outcome. The second study, initiated before 2017, was an observational cohort study (NCT01928108) enrolling adults Implications of all the available evidence with a history of urinary stone disease. This study compared use Very little evidence is available to guide clinicians about the best of two different smartphone applications to manually track strategies that will increase and sustain high fluid intake for water consumption, also using a behaviour change technique of secondary urinary stone disease prevention. The PUSH trial results self-monitoring. Neither the literature search nor ClinicalTrials. suggest that for many patients with urinary stone disease and gov reported study results. The other four trials of adherence low urine volume, it might be difficult to sustain high fluid intake interventions for fluid intake in prevention of urinary stone and thereby reduce stone recurrence. Taken together, these disease were initiated after PUSH started. The protocol results suggest that investigators might need to focus on describing the sipIT2 trial (with a primary endpoint of 24 h urine alternative adherence strategies and secondary prevention volume) was published in 2024. Two randomised controlled strategies that go beyond simply increasing fluid intake. challenge: the average increase in urine volume after status and reduce the incidence of type 2 diabetes.10 The counselling by physicians is only 300 mL per day.8 PUSH study intervention is designed as an adaptive, Therefore, the Prevention of Urinary Stones with multicomponent intervention leveraging multiple Hydration (PUSH) study focused on improving behaviour change techniques11 to promote adherence to adherence to high fluid intake, testing an intervention fluid intake. As part of a contingency management grounded in behaviour change theory, and focusing on approach, the PUSH study leverages financial rewards addressing common barriers to high fluid intake. for behaviour change, which is a well validated and Barriers to achieving and maintaining high fluid intake widely accepted way to incentivise a broad range of health are manifold: patients frequently identify lack of behaviours, including reducing substance use, increasing awareness of volume consumed or intake goals, physical activity, and promoting weight loss.12 Although forgetting to drink, and perceived need to drink as major contingency management is eective at eliciting impediments.9 Other barriers include practical concerns behaviour change, it might be more eective when such as lack of access to water, lack of bathroom access, utilised as part of a multicomponent behaviour change or competing time demands. Similar types of barriers to strategy.13 In what follows, we describe the key behaviour change exist for many diet-related health components of the PUSH intervention with the use of conditions, including obesity, for which the United States the standard taxonomy of behaviour change techniques Preventive Services Task Force recommends multi- (BCT)11 and the Behavior Change Intervention Ontology For more on BCIO see https:// www.bciontology.org/search component behavioural interventions to improve weight number (BCIO, found at bciosearch.org). In the PUSH 1172 Articles trial, the primary intervention to support increased water outside institutions were eligible. Screening, intake was providing a smart water bottle and loss- recruitment, and enrolment occurred primarily in framed financial incentives (providing aversive material connection with clinical care for urinary stone disease. consequence for BCT; BCIO:007243). Additional During and after the COVID-19 pandemic, participants intervention in the form of health coaching (structured could also be screened, recruited, and enrolled remotely. problem-solving—guide how to perform behaviour BCT; Recent symptomatic stone events were defined as BCIO:007050) was available to individuals who spontaneous stone passage or receiving a procedural consistently did not meet water intake targets over any intervention to remove stones within the previous 2 week period in the study, to help them to overcome 3 years, or a symptomatic stone event within 5 years if practical barriers to fluid intake. This type of adaptive new stone(s) were detected on subsequent diagnostic intervention strategy is common in health behaviour imaging such as ultrasound or CT. Eligible participants change, with additional support provided if a patient were required to have a baseline 24 h urine volume of does not meet goals.14 Health coaching and other less than 2·0 L per day for adults and adolescents aged low-touch approaches are commonly added to BCIs 12–17 years weighing at least 75 kg, and less than 25 mL when people are not meeting their goals.15 The rationale per kg bodyweight per day for adolescents weighing less for adding structured problem-solving for participants than 75 kg. Eligible participants were required to have falling short of their goals was intended to provide access to a mobile device that could sync with a assistance for identifying and solving barriers to meeting Bluetooth-enabled smart water bottle (appendix p 14).17 the prescribed water intake. Full eligibility criteria are available in the protocol, with The PUSH study selected recurrent symptomatic urinary the intention of enrolling participants with idiopathic stones as the primary endpoint, rather than the more stone disease (ie, not monogenic or from a surgical proximate outcome of increased fluid intake (or 24 h urine condition such as bariatric surgery, appendix p 94). Key output, which is the guideline-based clinical surrogate). exclusion criteria included monogenic stone disease, The ecacy of behavioural interventions should ideally be history of hyponatremia, recurrent urinary tract determined by clinically important outcomes that are infections, kidney transplantation, anatomic urologic meaningful to patients, because surrogate outcomes might abnormality, or gastrointestinal condition associated overestimate the benefits of the intervention.16 PUSH with excessive fluid losses. Adult participants provided tested the hypothesis that this adaptive, multi-component written informed consent and adolescents provided behavioural intervention to promote fluid intake would be verbal assent along with consent by legally authorised more ecacious to increase urine volume and reduce representatives. recurrent symptomatic stone events than a control group receiving guideline-based care from their usual physicians. Randomisation and masking Participants were randomly assigned in a 1:1 ratio to an Methods adaptive multicomponent behavioural intervention Study design focused on increasing fluid consumption (appendix p 5) The PUSH trial was an investigator-initiated, randomised or a control group with a follow-up of 2 years. controlled trial conducted between Oct 4, 2017 Randomisation was stratified by age group (adult or and April 16, 2024, at six medical centres in six US states adolescent), stone history (first-time or recurrent stone that participate in the Urinary Stone Disease Research former), and study site. Randomisation assignment was Network (USDRN). The rationale and design of the computer-generated remotely at the Scientific Data PUSH trial have been published previously.17 The Research Center (Durham, NC, USA). Every participant protocol was approved by the National Institute of received a Bluetooth-enabled smart water bottle that Diabetes and Digestive and Kidney Diseases (NIDDK) measured and recorded fluid intake (appendix pp 14–15). and institutional review boards of the Scientific Data Investigators, treating physicians, outcome assessors, Research Center and participating institutions. Patients and adjudicators were masked to group assignment. and members of the public reviewed and provided input Blinding of study participants, coordinators, or health on the protocol. Protocol amendments and rationale are coaches was not possible. detailed in the appendix (p 17). A data safety monitoring board convened by the NIDDK met regularly to assess Procedures trial progress and participant safety. Ethics approval was At enrolment, participants aged 18 years and older provided by the Duke University Health System underwent a low-dose, non-contrast CT scan and Institutional Review Board (Pro0008327). participants younger than 18 years had a renal ultrasound; all completed a 24 h urine collection. The Participants intervention consisted of a fluid prescription (set English-speaking patients aged 12 years and older with a measurable behaviour goal BCT BCIO:007300), financial recent symptomatic urinary stone event were screened. incentives to adhere to fluid prescription, health Patients receiving care at USDRN clinical centres and at coaching to overcome barriers to consuming more Articles fluids, and patient-selected approaches such as text available daily for the first 6 months. In months 6–18, messaging to maintain increased fluid intake. These the frequency of the days eligible for financial incentives components were selected based on specific behavioural was tapered from 80% to 15%, and no financial change techniques.11 The fluid prescription was the incentives were available in months 19–24 (BCT: provide additional daily fluid intake in excess of baseline intake reduced frequency of aversive consequence for behaviour required to achieve urine volume of more than 2·5 L BCT BCIO:007273).11,17 Participants randomly assigned to per day, as recommended by American Urological the intervention group were required to synchronise Association guidelines,4 and was calculated with the use their water bottle and mobile device daily to be eligible of the baseline 24 h urine volume (appendix p 5). The for financial incentives. Participants in the intervention fluid prescription (BCT: goal setting11 BCIO:007300) was group were also oered structured problem solving to be consumed from the smart water bottle. Participants (health coaching intervention) if the daily fluid in the intervention group were eligible for a daily, loss- prescription was not met for at least two 2-week periods framed financial incentive of US$1·50 when they in the first 6 months. Structured problem solving was consumed the individualised fluid intake prescription designed to facilitate identifying barriers to increasing from the smart water bottle (contingency management, fluid intake and developing solutions to overcome them, BCT: material reward11). This financial incentive was prioritising those most practicable (BCT: review behaviour goal [BCIO:007011, action planning BCIO: 007010]).11,17 A fidelity assessment, conducted by a 2429 participants consented trained reviewer on a sample of both initial and follow-up coaching interactions, ensured consistency of coaching across institutions.18 The fidelity assessment showed 2429 screened that, on average, more than 90% of the required elements were covered in each initial and follow-up 581 not eligible coaching interaction. Participants received low-touch interventions of their choosing among social incentives (eg, support partner) or low-cost interventions (text 1848 eligible message reminders) to help to sustain new habits of fluid consumption during months 19–24 (BCT: social 1658 randomly assigned support BCIO:007028, prompts or cues BCIO:00708111). Participants in the control group were provided with guideline-concordant recommendations to increase fluid consumption to achieve urinary output of at least 2·5 L 826 intervention group 832 control group daily in addition to usual stone prevention care.4,5 They 826 eligible for daily financial 98 adolescent incentive 734 adult were provided with the smart water bottle, but its use was 518 qualified for structured 281 first-time formers not required (appendix p 5). All participants in each problem solving 551 recurrent formers 99 adolescent group continued to receive guideline-concordant care 727 adult with their kidney stone clinician. 273 first-time formers 553 recurrent formers Outcomes The primary outcome was symptomatic stone recurrence, 826 24 h urine volume measured 832 24 h urine volume measured defined as spontaneous stone passage with symptoms or at baseline at baseline a procedural intervention for a symptomatic or asymptomatic stone. Participants received questionnaires 150 discontinued 141 discontinued electronically to report stone events every 3 months for 92 lost to follow-up 107 lost to follow-up the duration of the study. Reported events were reviewed 44 withdrawal by participant 23 withdrawal by participant 7 pregnancy 5 pregnancy and classified as confirmed clinical events, participant- 4 investigator decision 2 investigator decision reported, or non-events by an adjudication committee 2 technical problems 2 protocol violation comprising expert clinicians who were masked to study 1 withdrawal by parent or 2 death guardian 0 technical problems group allocation.19 Confirmed clinical stone events 0 protocol violation 0 withdrawal by parent or required typical stone symptoms (eg, flank pain) in 0 death guardian addition to objective documentation of stone passage or surgical intervention (appendix p 173). Events with typical 676 completed 24-month 691 completed 24-month symptoms and self-described passage of a stone without follow-up follow-up objective documentation of passage were classified as 826 included in primary analysis 832 included in primary analysis participant-reported; a detailed description of the adjudication process has been separately published.19 Figure 1: CONSORT diagram All randomly assigned patients included in the primary analysis. Confirmed and participant-reported events met the 1174 Articles primary outcome. All other reported incidents were degrees of freedom for the F-statistic were approximated considered non-events. with the use of the Kenward-Roger method. Imaging Secondary outcomes included change in 24 h urine and composite outcomes were analysed as binary volume (a mechanistic outcome); urinary symptoms; outcomes at 24 months with logistic regression models. radiographic outcomes consisting of new stone No interim analyses of the primary and secondary formation and growth of an existing stone by at least outcomes were planned or performed. No missing 2 mm in any dimension; and a composite outcome of outcomes were imputed. For the primary outcome, we symptomatic stone recurrence, new stone formation, or used a time-to-first-event approach, with participants growth of existing stone(s). 24 h urine collections to who did not have any stone events during the 24-month measure urine volume were done at 6, 12, 18, and follow-up censored at the end of their observation 24 months. Participants were considered adherent if they achieved at least two 24 h urine volumes of at least 2·5 L Intervention Control Total (n=1658) per day for adults or at least 30 mL/kg bodyweight per group (n=826) group (n=832) day for adolescents weighing less than 75 kg at 6, 12, 18, Age, median (IQR), years 45 (30–60) 44 (27–58) 44 (29–59) and 24 months. 24 h urine collections were considered Age group, median (IQR), years adequate if creatinine excretion rate (mg/kg per day) was Adult 49 (35–61) 48 (34–59) 48 (36–60) within two standard deviations of the mean for the Adolescent 15 (14–16) 16 (14–16) 15 (14–16) cohort. Urinary symptoms were recorded at baseline and Female 469 (56·8%) 477 (57·3%) 946 (57·1%) every 6 months with the use of the validated Male 357 (43·2%) 355 (42·7%) 712 (42·9%) Comprehensive Assessment of Self-reported Urinary Race Symptoms.20 Radiographical outcomes were assessed White 732 (88·6%) 719 (86·4%) 1451 (87·5%) with the use of validated software that automated Black or African American 55 (6·7%) 58 (7·0%) 113 (6·8%) analyses of CT scans.21 To ensure accuracy and reliability Native American 0 (0·0%) 3 (0·4%) 3 (0·2%) for this trial, the performance of the analysis software Asian 22 (2·7%) 25 (3·0%) 47 (2·8%) was revalidated by study investigators with the use of Native Hawaiian or other Pacific Islander 2 (0·2%) 2 (0·2%) 4 (0·2%) images from trial participants (appendix p 194).22 Safety Other or unknown* 8 (1·0%) 11 (1·2%) 19 (1·1%) monitoring included report of hyponatremia requiring Multiracial 7 (0·8%) 14 (1·7%) 21 (1·3%) hospitalisation, which was evaluated systematically by Ethnicity review of all hospitalisations during the study. Not Hispanic or Latino 761 (92·1%) 757 (91·0%) 1518 (91·6%) Hispanic or Latino 46 (5·6%) 56 (6·7%) 102 (6·2%) Statistical analysis Not reported 13 (1·6%) 10 (1·2%) 23 (1·4%) Statistical analysis was done by personnel masked to Unknown 6 (0·7%) 9 (1·1%) 15 (0·9%) treatment assignments. A sample size of 1642 participants Household income (821 per group) provided at least 80% power to detect <$90 000 323 (39·1%) 305 (36·7%) 628 (37·9%) 30% relative risk reduction in stone recurrence in the ≥$90 000 365 (44·2%) 371 (44·6%) 736 (44·4%) intervention group with the use of a log-rank test for Other* 138 (16·7%) 156 (18·8%) 294 (17·7%) time to first symptomatic stone event, with a two-sided Thiazide diuretic at baseline 61 (7·4%) 60 (7·2%) 121 (7·3%) type I error rate of 0·05. A 15% event rate was assumed Potassium citrate at baseline 92 (11·1%) 96 (11·5%) 188 (11·3%) for the control group,1 and a 20% attrition was assumed Median baseline 24 h urine total volume, L, 0·85 0·85 0·85 over the 24-month follow-up period. median (IQR), number of adolescents (0·66–1·14), 99 (0·65–1·05), 98 (0.66–1·10), 197 The primary outcome was evaluated according to the Median baseline 24 h urine total volume, L, 1·29 1·30 1·30 intention-to-treat principle and was analysed as time-to- (IQR), number of adults (0·98–1·61), 727 (1·01–1·56), 734 (1·00–1·58), 1461 event by treatment group with a log-rank test. Cumulative Baseline 24 h urine calcium, mg per total 190 190 190 event rates were calculated for each group as a function of volume, median (IQR), number of adults (129–261), 552 (127–256), 544 (128–259), 1096 time from randomisation (Kaplan–Meier method). Data Baseline 24 h urine citrate, mg per total 553 534 544 collected on subsequent recurrent events of symptomatic volume, median (IQR), number of adults (383–757), 538 (376–729), 532 (378–746), 1070 stones were analysed by treatment group with the use of Baseline 24 h urine pH, mean (IQR), number of 6·00 6·04 6·02 adults (5·65–6·41), 671 (5·66–6·41), 685 (5·65–6·41), 1356 the Andersen–Gill model with robust standard errors to Baseline 24 h urine osmolality, mOsm/kg, 662 653 657 account for heterogeneity and correlation between median (IQR), number of adults (471–847), 432 (463–815), 469 (469–834), 901 recurrent stone events within a participant. Baseline 24 h urine sodium mEq/TV, median 140 134 137 24 h urine volume measurements at baseline and (IQR), number of adults (103–183), 549 (99–177), 540 (101–179),1089 6, 12, 18, and 24 months were analysed with a repeated- Baseline 24 h urine potassium, mEq/TV, 50 48 49 measures mixed-eects model, with study site treated median (IQR), number of adults (36–66), 538 (36–62), 525 (36–64), 1063 as a random eect, and treatment and visit as fixed Data are number (%), unless otherwise indicated. mEq/TV=milliEquivalents per total volume. mOsm=milliosmole eects. Variance components were used as the osmotic concentration. TV=total volume. $=US$.*Includes “don’t know” and “prefer not to answer” responses. variance–covariance structure. The model also included Table: Demographic and clinical characteristics of study participants a treatment-by-visit interaction term, and denominator Articles period. For the secondary outcome of 24 h urine volume over time (repeated measures), a mixed-eects model was used, and no imputation was required. Prespecified landmark analyses were done to exclude stone events that occurred within 30, 60, and 90 days of 30 randomisation. These analyses were performed with the use of the same methods as the primary outcome. Planned subgroup analyses for the primary outcome 20 were done with the use of Cox proportional hazards models by including interaction terms for sex, age, clinical centre, provider, and adherence. Participants were 10 considered adherent if they achieved at least two 24 h urine volumes of at least 2·5 L per day for adults or at least 30 mL/kg bodyweight per day for adolescents 0 weighing less than 75 kg at 6, 12, 18, and 24 months. A 0 90 180 270 360 450 540 630 720 810 prespecified sensitivity analysis was done for surgical Number at risk Time since randomisation (days) removal of asymptomatic stones requiring at least one of Intervention group 826 770 725 693 663 631 606 588 454 112 the following criteria: stone size of at least 4 mm in any Control group 832 791 752 717 674 651 628 608 472 116 dimension, mobile stone, associated haematuria, or Figure 2: Symptomatic recurrence of urinary stones recurrent urinary tract infection with the use of the same 1176 )%( tneve enots fo ytilibaborP Patients with stone, intervention: 154/826 (18·6%) Patients with stone, control: 165/832 (19·8%) Kaplan-Meier rate at 2 years for intervention group: 19·6% (95% Cl 17·0–22·6%) Kaplan-Meier rate at 2 years for control group: 21·1% (95% Cl 18·4–24·1%) Intervention group Control group Number of n/N (%) per 100 patient-years p interaction patients (n) Intervention group Control group All patients 1658 154 (18·6%) 11·22 165 (19·8%) 11·65 Stone history 0·34 First time 554 30/273 (11·0%) 6·23 41/281 (14·6%) 7·95 Recurrent 1104 124/553 (22·4%) 13·91 124/551 (22·5%) 13·77 Age group 0·33 Adult 1461 139/727 (19·1%) 11·59 144/734 (19·6%) 11·57 Adolescent 197 15/99 (15·2%) 8·63 21/98 (21·4%) 12·26 Sex 0·92 Male 712 71/357 (19·9%) 11·91 75/355 (21·1%) 12·59 Female 946 83/469 (17·7%) 10·69 90/477 (18·9%) 10·97 Race 0·61 Black or African American 113 8/55 (14·5%) 8·75 11/58 (19·0%) 11·07 Other 1523 145/764 (19·0%) 11·44 149/759 (19·6%) 11·54 Stone care provider specialty 0·26 Urologists 1164 107/574 (18·6%) 11·05 125/590 (21·2%) 12·44 Others 494 47/252 (18·7%) 11·61 40/242 (16·5%) 9·72 Clinical Centre 0·35 UPenn/CHOP 334 29/168 (17·3%) 9·59 37/166 (22·3%) 12·53 UTSW 309 24/154 (15·6%) 8·50 29/155 (18·7%) 10·39 UWash 309 36/154 (23·4%) 15·75 33/155 (21·3%) 13·29 WUSTL 375 55/186 (29·6%) 19·88 56/189 (29·6%) 18·89 CCF 198 9/98 (9·2%) 5·40 9/100 (9·0%) 5·04 Mayo 133 1/66 (1·5%) 0·86 1/67 (1·5%) 0·85 Adherence based on 2·5 L criteria 0·26 Yes 1124 113/567 (19·9%) 11·19 125/557 (22·4%) 12·62 No 534 41/259 (15·8%) 11·30 40/275 (14·5%) 9·41 0·25 0·50 1·00 2·00 Favours intervention Favours control Figure 3: Subgroup analyses of symptomatic recurrence of urinary stones UWash=University of Washington. WUSTL=Washington University in St.Louis. CCF=Cleveland Clinic. Mayo=Mayo Clinic. UPenn/CHOP=University of Pennsylvania/ Children’s Hospital of Philadelphia. UTSW=University of Texas Southwestern. *Adherence defined as at least 2·5 L urine output per 24 h on at least two 24 h collections for adult participants. Additionally, the 24 h urine collection group is required to have creatinine mg/kg per day within 2 SD of mean Cr mg/kg per day for the cohort. Articles methods as the primary outcome. As a sensitivity analysis, 1·9 a win ratio analysis was done with the use of the p<0·0001 Finkelstein-Schoenfeld method with the hierarchical 1·8 p=0·009 p=0·003 order of: (1) symptomatic stone event, (2) new stone 1·7 formation, and (3) stone growth. A prespecified economic p=0·048 analysis will be published separately. 1·6 All statistical comparisons were done with the use of 1·5 two-sided significance tests with α=0·05 and SAS software (version 9.4). All primary and secondary 1·4 outcome analyses accounted for the randomisation strata 1·3 (ie, age group, stone history, and study site). Full analytical plan details are provided in the statistical 1·2 analysis plan (appendix p 142). This study is registered 1·1 with ClinicalTrials.gov, NCT03244189. 1·0 Baseline Month 6 Month 12 Month 18 Month 24 Role of the funding source This is a cooperative agreement; that means there is substantial federal scientific or programmatic involvement in the research activities. The NIDDK Project Scientist (ZK) was involved in the design and development of the Figure 4: 24 h urine volume by timepoint and treatment group (mixed-effects model) clinical protocol, preparation of questionnaires and other FI (%)=loss-framed financial incentive. % indicates percentage of days loss-framed incentive was available to participants. FI Taper=financial incentive taper. Availability tapered from 75% of days (month 13) to 15% of days data recording forms, coordination of research, statistical (month 18). Participants blinded to which day(s) financial incentive was available. No financial incentive available evaluations and analyses of data, and the publication of in months 19–24. SPS=structured problem solving. Low touch=low touch interventions to promote adherence results. The programme was overseen by an independent (eg, support partner, reminder via text communication). NIDDK Program Ocial (CM). randomisation (appendix p 9). A hierarchical order (win Results ratio) analysis did not show a dierence between 2429 patients underwent screening between Oct 23, 2017, treatment groups (appendix p 10). and Feb 17, 2022. Of these patients, 1658 were randomly 24 h urine volume increased from baseline in both assigned to the intervention group (n=826) or control groups and was higher in the intervention group at group (n=832; figure 1). Median age was 44 years months 6, 12, 18, and 24 compared with the control group (IQR 29–59), and 946 (57%) participants were female (figure 4, appendix p 11). Urinary storage symptoms of (table). 441 (30%) of 1461 of adults and 114 (58%) of frequency, urgency, and nocturia were greater in the 197 adolescents had first-time stone formation. In the intervention group than the control at months 6 intervention group, first-time stone formers included (p=0·050) and 12 (p=0·014) but not at other timepoints 217 (29·8%) of 727 adults and 57 (57·6%) of 99 adolescents. (appendix p 13). There was no dierence in stone growth In the control group, first-time stone formers consisted of at least 2 mm (odds ratio 1·44, 95% CI 0·91–2·29) or of 224 ([30·5%] of 734) adults and 57 ([58·2%] of 98) new stones (0·99, 0·72–1·37) between groups from adolescents. Baseline median 24 h urine volume was 1·30 baseline to end-of-study imaging (appendix p 12). The (IQR 1·00–1·58) L per day in adults and 0·85 composite outcome of symptomatic stone recurrence, (0·66–1·10) L per day in adolescents (table). new stone formation, or stone growth of at least 2 mm At a median follow-up of 738 (IQR 711–778) days, was also not statistically dierent between groups 154 (19%) participants had a symptomatic stone event in (appendix p 12). the intervention group compared with 165 (20%) in the No participants had hyponatremia requiring control group (hazard ratio 0·96, 95% CI 0·77–1·20). hospitalisation. In the intervention group, 12 (1%) There was no dierence in the cumulative risk of participants had asymptomatic hyponatremia versus symptomatic stone recurrence between the groups two (<1%) participants in the control group (p=0·018). (figure 2). Subgroup analyses showed no heterogeneity of There were no study-related serious adverse events in treatment eect by sex, age, clinical centre, or provider either group. (figure 3). In addition, adherence to the intervention, defined as meeting at least two 24 h urine collections at or Discussion more than the target value (2·5 L per day for adults), did To the best of our knowledge, the PUSH trial is the not result in a dierence in the adherence subgroups largest randomised controlled trial designed to improve (figure 3). In sensitivity analyses, there was no dierence adherence to fluid intake for secondary prevention of between groups when excluding individuals who urinary stones to date. There are several key findings. underwent surgery for an asymptomatic stone or stone Participants in the behavioural intervention group events that occurred within 30, 60, and 90 days of achieved a greater urine volume compared with )L( emulov eniru h Intervention group Control group FI (100%) ±S PS FI (80%) ± SPS FI taper Low touch (75% →15%) +l ow touch Articles participants in the control group. However, this increase remained modest. This outcome might, in part, reflect a in urine volume did not result in a decrease in recurrent unique negative eect of the intervention for this trial in symptomatic stone events over 2 years of follow-up. that urinary symptoms are often exacerbated by Second, urinary symptoms were greater in the increased fluid intake. Participants assigned to the intervention group at 6 and 12 months. Finally, there was intervention group reported greater urinary symptoms no dierence between groups in the radiographical at months 6 and 12—timepoints at which the dierence outcomes of new stone formation or stone growth at end in urine volume between the two groups was greater of study. (appendix p 13). As fluid intake increases, urine output Increasing fluid intake to increase urine volume has is expected to rise, which in some patients might result long been a cornerstone of secondary prevention of in expected, but potentially bothersome, urinary urinary stone disease, with the goal of diluting the symptoms such as frequency or nocturia. These parallel concentration of stone-forming salts in urine. Both the increases in urine volume and urinary symptoms might American Urological Association4 and the European reflect the challenges that aect some people who form Association of Urology guidelines5 recommend fluid stones when trying to adhere to an increased fluid intake intake sucient to produce a urine volume of at least goal. 2·5 L per day as a prevention strategy for patients with Findings from several randomised controlled trials urinary stone disease. These recommendations are have shown that interventions can improve healthy partially based on a single randomised controlled trial of behaviours such as smoking cessation, weight loss, and 199 participants, which showed that greater fluid intake physical activity. 12,23,24 Broad adoption of these approaches resulting in 2·5 L of urine per day on average led to has been hindered by two key limitations: durability of fewer recurrent stones and longer time to stone events the health behaviour change and the use of surrogate compared with a group that had an average of only 1 L of rather than clinically meaningful outcomes. We designed urine per day.7 Largely based on the reduction in the PUSH trial to address these limitations.17 First, we recurrent stone events reported in that trial, increased used a clinically meaningful primary outcome fluid intake is now considered standard for the (symptomatic stone recurrence) rather than the secondary prevention of urinary stone disease.4,5 mechanistic surrogate outcome of increased urine However, in real-world care, it is challenging for patients volume.25 Second, we structured the intervention to to increase their urine volume to meet this goal, despite enhance durability of the eect through habit formation the eorts of various providers in multiple clinical with the use of behavioural approaches known to settings.8 improve adherence, including an initial loss-framed In the PUSH trial, adult participants in the intervention incentive, tapering of incentives with intermittent group increased urine volume (vs baseline) by 600 mL reinforcement,11,26 and additional components that per 24 h at 6 months, compared with only 360 mL per operate on structural barriers not addressed by financial 24 h in the control group, but this dierence diminished incentives. Adaptable patient-selected strategies allowed over time. An important aspect of the PUSH trial was for individualisation of plans to maximise success of the that participants in the control group continued to receive intervention. The positive eect on a surrogate, but less ongoing care from their existing stone clinician, which patient-relevant outcome (24 h urine volume) highlights included increasing fluid intake and dietary the importance of following interventions to meaningful recommendations per their usual practice, compared clinical endpoints in adherence trials and should inform with the Borghi and colleagues’ trial,7 in which the design of future health behaviour trials. participants in the control group received no additional Our study has limitations. Participants were recruited fluids. Accordingly, the increase in urine volume in the from academic, tertiary care centres that might treat control group in our study and the resulting smaller participants with more severe disease. We did not assess dierence in urine volume between the two groups or control for additional fluid intake not measured by the (figure 4) might explain the similarity between groups for smart water bottle or other dietary factors, although stone-related outcomes. randomisation should balance these unmeasured There are myriad perceived barriers to fluid intake confounders. The follow-up period was only 2 years; such as not liking the taste of water, not experiencing however, the PUSH trial exceeded the estimated event thirst, failure of habit formation for fluid intake, and rate, and the Kaplan–Meier curves were nearly parallel, feeling bloated with consumption. Additionally, many suggesting that a longer follow-up period for PUSH is people do not understand the association between fluid unlikely to change the results. Insight into what intake and stone formation.9 In this study, we attempted components of the intervention were eective (or not) to address barriers to fluid intake through health would have required a larger study design (eg, factorial), coaching and structured problem solving, theorising which was not feasible. These factors could be assessed in that patient education and providing individualised an exploratory secondary analysis. Females made solutions would optimise success of the intervention. up 57% of the study population. Although the prevalence However, the dierence in urine volume between groups of urinary stone disease among females in the USA is 1178 Articles closer to 44%, the gender gap is narrowing worldwide.27 Lakshmi Ananthakrishnan; Local Referring Providers: Brett A Johnson, The predominance of female participants might reflect Yair Lotan, Orson W Moe, Margaret S Pearle, Craig A Peters, Khashayar Sakhaee, Li Song; Referring Collaborators (for participants gender dierences in willingness to participate in clinical recruited remotely): Timothy Y Tseng (University of Texas Health-San research, as females are more likely than males to enrol in Antonio), Ryan L Steinberg (University of Iowa), Joseph J Crivelli behavioural intervention trials28 (median 56·7%, (University of Alabama); UT Southwestern Study Sta: 95% CI 40·7–76·0% [n=1346 trials]). Utilisation of Sudeepa Bhattacharya (Program manager), Martinez Hill (CRC), Esperanza Jackson (CRC), Alejandra Lozano (CRC), Corey Nixon (CRC), adjunctive stone prevention medications (ie, thiazides and Brooke Piskator (CRC), Cynthia Rangel (CRC), Jesse Tarbutton (CRC), potassium citrate) was similar between groups at baseline Madeline Worsham (Coach), John R Poindexter (Local Database (table). We did not assess participant acceptability with the Manager). UT Southwestern CTSA Program, grant UL1TR003163. intervention, although the dropout rate was lower than University of Washington, Seattle, WA, USA: Principal Investigators: Jonathan D Harper, Hunter Wessells; co-investigators: projected. Finally, there is the risk of co-intervention Fionnuala Cormack, Mathew Sorensen, Karyn Yonekawa; Study through treatment in a specialty stone clinic, known as the Coordinators: Holly Covert, Tristan Baxter, Elsa Ayala. Research stone clinic eect.29 This eect, along with frequent study Assistants: Grace Marshall, Grace Cho. Local referring providers: contact with the control group participants, could have Rob Sweet, Lisa Gill PA-C, Brianna Gutierrez. Remote referring providers: Ryan Hsi, Thomas Chi, David Tzou, Patrick Samson, Ian Metzler, biased results toward the null hypothesis. These Stephen Confer, Noah Canvasser. Washington University in St Louis, limitations notwithstanding, several features of the trial St Louis, MO, USA: Principal Investigators: Alana C Desai, H Henry Lai; strengthen the validity of outcomes. The study population co-investigators: Vincent Mellnick, Douglas Coplen; Study Coordinators: was the largest to date for a stone prevention trial, with Juanita Taylor, Aleksandra Klim, Deborah Ksiazek, Vivien Gardner. Recruiting Centres: Cleveland Clinic, Cleveland, OH: Principal adequate power to detect meaningful dierences, and the Investigator: Sri Sivalingam. Co-investigators: Katherine Dell, Juan Calle, number of primary outcome events exceeded projections. Manoj Monga, Louisa Ho, Harmenjit Brar; Referring Practitioners: Additionally, we exceeded the target enrolment, with an Heidi Digennaro, Tiany Loboda; Study Coordinators: Lauren Grimm, attrition rate lower than projected. Multiple comple- Marina Markovic. Dr Monga resigned from the PUSH DSMB prior to Cleveland Clinic Foundation joining the study as a Recruiting Center. mentary methods were used to ascertain outcomes to Mayo Clinic, Rochester, MN: Principal Investigator: John Lieske; reduce under-reporting of events. co-investigators: Kevin Koo, Fernanda Bellolio, Michelle Bouquet, Although there was no dierence in stone recurrence Andrew Rule, Stephen Erickson, Mira Keddis, Aaron Potrezke, between the groups, our trial has important implications Andrea Ferrero, David Sas; Study Coordinators: Angela Waits, Courtney Lenort. Dr. Rule resigned from the PUSH DSMB prior to Mayo for behavioural science and for stone prevention eorts. Clinic Foundation joining the study as a Recruting Center. Scientific Data This intervention increased urine volume but did not Research Centres: Duke Clinical Research Institute, Duke University, decrease the long-term clinical goal of stone recurrence. Durham, NC: Principal Investigators: Charles D Scales, The results of the PUSH study do not undermine the Hussein R Al-Khalidi; co-investigators: Kevin Weinfurt, Hayden Bosworth; Statistician: Hongqiu Yang; Project Leadership: importance of increasing fluid intake for stone prevention, Laura Johnson, Davy Andersen, Paul Camarena; Lead CRA: as this remains a low-cost, low-risk intervention with Sharon Settles; CRA: Angela Venetta; Data Manager: Omar Thompson, likely benefits based on previous literature. Rather, our Robert Baldwin. National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), Bethesda, MD: Project Scientist: Ziya Kirkali; study suggests that although contingency management Program Ocial: Christopher Mullins. Data and Safety Monitoring intervention with health coaching for non-adherent Board: John Denstedt (DSMB Chair), Dean G Assimos, Scott Cohen, participants was insucient to yield significant clinical Gary Curhan, Michael A. Freeman, David Goldfarb, Amy Krambeck, benefit, relative to participants in the control group, Rebecca A. Krukowski, Jeannette Lee, Manoj Monga, Andrew Rule, Christopher Schmid, Marshall Stoller, Eric Taylor, MD, future investigations could apply optimisation study Jennifer Temple, PhD. Drs. Monga and Rule resigned from the DSMB designs (ie, factorial designs, or sequential, multiple prior to Cleveland Clinic and Mayo Clinic joining USDRN as PUSH assignment, randomised trial designs) within a Recruitment Centers, to avoid any conflicts of interest. multiphase optimisation strategy framework to determine Contributors what strategies yield the best results for most people. ACD, JDH, GET, and CDS: study design, investigation, data collection, Additional qualitative research might yield key insights analysis plan, writing of the original draft, review and editing, and funding acquisition. NMM, HHL, PPR, and HW: study design, into patient barriers to fluid intake that would inform investigation, data collection, analysis plan, review and editing, and future intervention design. A more personalised medicine funding acquisition. SS and JCL: investigation, data collection, analysis approach could be attempted to address individual plan, review and editing, and funding acquisition. HY: study design, data dierences in motivations to consume water and thereby curation, formal analysis, writing of the original draft, and review and editing. HRAl-K: study design, investigation, data collection, analysis prevent recurrent stones. plan, formal analysis, review and editing, and funding acquisition. Urinary Stone Disease Research Network ZK: study design, analysis plan, review and editing, and supervision. The following individuals were instrumental in the planning and CDS and HRAl-K had full access to all the blinded data in the study. conduct of the PUSH trial at each of the participating institutions. HRAl-K and HY had direct access to and verified the underlying data Clinical Centres: University of Pennsylvania/Children’s Hospital of and take responsibility for the integrity of the data analysis. All authors Pennsylvania, Philadelphia, PA, USA: Principal Investigators: contributed to the drafting and review of the manuscript and agreed to Peter P Reese, Gregory E Tasian. Co-investigators: Sandra Amaral, submit it for publication. All authors had permission to access the raw Janet Audrain-McGovern, Justin Ziemba, Kevin Volpp; Project Manager: data in this study. Adam Mussell; Study Coordinators, Gabrielle Perez, Brittney Henderson, Declaration of interests Kristen Koepsell, Reiley Broms. University of Texas Southwestern Medical JCL declares grants or contracts from Alnylam, Dicerna/Novo Nordisc, Center, Dallas, TX, USA: Principal Investigator: Naim M Maalouf; Arbor, Oxalosis, and Hyperoxaluria Foundation; consulting fees (paid to co-investigators: Jodi A Antonelli, Linda A Baker, Articles Mayo Clinic) for scientific advisory board participation from Alnylam, 5 Skolarikos A, Jung H, Neisius A, et al. EAU Guidelines on Dicerna/Novo Nordisc, and Arbor; support for attending meetings and/ urolithiasis. EAU guidelines. https://uroweb.org/guidelines/ or travel from Japanese Society of Urology—Tokyo; declares Data Safety urolithiasis/chapter/guidelines (accessed June 20, 2025). Monitoring Board participation for Alnylam, Dicerna/Novo Nordisc, 6 Bao Y, Tu X, Wei Q. Water for preventing urinary stones. Arbor; and funding for an observational study from the National Cochrane Database Syst Rev 2020; 2: CD004292. Institutes of Health. PPR declares an investigator-initiated grant from 7 Borghi L, Meschi T, Amato F, Briganti A, Novarini A, Giannini A. Merck paid to their institution to support trials of transplanting organs Urinary volume, water and recurrences in idiopathic calcium from deceased donors with hepatitis C infection into uninfected nephrolithiasis: a 5-year randomized prospective study. J Urol 1996; 155: 839–43. recipients; an investigator-initiated grant from Gilead to the institution to support trials of transplanting organs from deceased donors with 8 Parks JH, Goldfischer ER, Coe FL. Changes in urine volume accomplished by physicians treating nephrolithiasis. J Urol 2003; hepatitis C infection into uninfected recipients; is a co-investigator on 169: 863–66. grant from eGenesis to the institution for preclinical research on 9 Rice P, Archer M, Davis T, Pietropaolo A, Somani B. Patient xenotransplant technology (no product yet on the market); perception and barriers with fluid hydration: a prospective face-to- a co-investigator on grant to institution for studies of EBV infection and face interview and counselling from a university hospital stone lymphomas after transplant; and received an investigator-initiated grant clinic. Cent European J Urol 2023; 76: 239–44. from the Leonard Davis Institute at the University of Pennsylvania, 10 Curry SJ, Krist AH, Owens DK, et al. Behavioral weight loss supported by a gift from Monogram Health, to develop educational interventions to prevent obesity-related morbidity and mortality in resources for kidney transplantation. PPR declares honoraria from adults: US Preventive Services Task Force recommendation various universities for giving academic talks or being visiting Professor, statement. JAMA 2018; 320: 1163–71. as well as expert testimony working for the defendants for two 11 Michie S, Richardson M, Johnston M, et al. The behavior change engagements involving cases of individual patients who needed kidney technique taxonomy (v1) of 93 hierarchically clustered techniques: transplantation to estimate lifelong costs of transplant care; is a member building an international consensus for the reporting of behavior of the Data Safety Monitoring Board for NIH-funded trials of decision change interventions. Ann Behav Med 2013; 46: 81–95. making for patients with end-stage kidney disease and those needing 12 Volpp KG, John LK, Troxel AB, Norton L, Fassbender J, palliative care (no payments); and is an associate editor of the American Loewenstein G. Financial incentive-based approaches for weight Journal of Kidney Diseases. HW declares grants from National Institutes loss: a randomized trial. JAMA 2008; 300: 2631–37. of Health/National Institute of Diabetes and Digestive and Kidney 13 Secades-Villa R, González-Roz A, Vallejo-Seco G, et al. Additive Diseases National Research Service Award Training Core, and Bladder eectiveness of contingency management on cognitive Research. HRA-K declares participation on a Data Safety Monitoring behavioural treatment for smokers with depression: six-month Board of Data and Safety Monitoring Board for National Institutes of abstinence and depression outcomes. Drug Alcohol Depend 2019; 204: 107495. Health/National Heart Lung and Blood Institute, MedPace, and Novartis. CDS declares participation on a Data Safety Monitoring Board of the 14 Almirall D, Nahum-Shani I, Sherwood NE, Murphy SA. Introduction to SMART designs for the development of adaptive University of Michigan PCORI-funded study. All other authors declare interventions: with application to weight loss research. no competing interests. Transl Behav Med 2014; 4: 260–74. Data sharing 15 Yan X, Dunne DM, Impey SG, et al. A pilot sequential multiple After publication, de-identified data from the trial database will be assignment randomized trial (SMART) protocol for developing an transferred to the NIDDK Central Data & Biorepository (https:// adaptive coaching intervention around a mobile application for repository.niddk.nih.gov/home). Proposals for data access can be athletes to improve carbohydrate periodization behavior. submitted via email (USDRN@duke.edu) or directly to the NIDDK Contemp Clin Trials Commun 2022; 26: 100899. Central Data & Biorepository. Data will be made available to those with 16 Ciani O, Buyse M, Garside R, et al. Comparison of treatment eect an approved proposal and executed data access agreement. sizes associated with surrogate and final patient relevant outcomes in randomised controlled trials: meta-epidemiological study. BMJ Acknowledgments 2013; 346: f457. ACD’s current aliation is University of Washington School of 17 Scales CD Jr, Desai AC, Harper JD, et al. Prevention of urinary Medicine, Seattle, WA. HHL’s current aliation is University of Iowa stones with hydration (PUSH): design and rationale of a clinical Carver College of Medicine, Iowa City, IA. Both were at Washington trial. Am J Kidney Dis 2021; 77: 898–906.e1. University in St Louis (noted above) during the conduct of the PUSH 18 Reese PP, Shah S, Funsten E, et al. Using structured problem trial. PPR’s current aliation is Vanderbilt University, Nashville, TN. solving to promote fluid consumption in the prevention of urinary He was at the University of Pennsylvania (noted above) during the stones with hydration (PUSH) trial. BMC Nephrol 2024; 25: 183. conduct of the PUSH trial. This research was funded by the National 19 Wessells H, Lieske JC, Lai HH, et al. Adjudication of self-reported Institute of Diabetes and Digestive and Kidney Diseases DK110986 symptomatic stone recurrence in the prevention of urinary stones (Washington University in St Louis—ACD, HHL); DK110961 (Children’s with hydration trial. Urology 2024; 194: 27–35. Hospital of Philadelphia/ University of Pennsylvania— PPR, GET); 20 Weinfurt KP, Grith JW, Flynn KE, et al. The comprehensive DK110954 (University of Washington—JDH, HW); DK110994 (University assessment of self-reported urinary symptoms: a new tool for of Texas Southwestern—NMM); DK110988 (Duke University—HRA-K, research on subtypes of patients with lower urinary tract symptoms. J Urol 2019; 201: 1177–83. CDS—subcontracts from Duke to Mayo [JCL] and Cleveland Clinic [SS]). 21 Babajide R, Lembrikova K, Ziemba J, et al. Automated machine We thank Elizabeth E S Cook of the Duke Clinical Research Institute for learning segmentation and measurement of urinary stones on CT providing editorial assistance. We thank Sarah Cantrell of the Duke scan. Urology 2022; 169: 41–46. University Medical Library for providing assistance with the literature 22 Tasian GE, Maalouf NM, Harper JD, et al. Validation of an search. automated CT image analysis in the prevention of urinary stones with hydration trial. J Endourol 2025; 39: 953–59. References 23 Charness G, Gneezy U. Incentives to exercise. Econometrica 2009; 1 Rule AD, Lieske JC, Li X, Melton LJ 3rd, Krambeck AE, 77: 909–31. Bergstralh EJ. The ROKS nomogram for predicting a second symptomatic stone episode. J Am Soc Nephrol 2014; 25: 2878–86. 24 Volpp KG, Troxel AB, Pauly MV, et al. A randomized, controlled trial of financial incentives for smoking cessation. N Engl J Med 2 Bryant M, Angell J, Tu H, Goodman M, Pattaras J, Ogan K. Health 2009; 360: 699–709. related quality of life for stone formers. J Urol 2012; 188: 436–40. 25 Stout TE, Lingeman JE, Krambeck AE, et al. A randomized trial 3 Moe OW. Kidney stones: pathophysiology and medical evaluating the use of a smart water bottle to increase fluid intake in management. Lancet 2006; 367: 333–44. stone formers. J Ren Nutr 2022; 32: 389–95. 4 Pearle MS, Goldfarb DS, Assimos DG, et al. Medical management of kidney stones: AUA guideline. J Urol 2014; 192: 316–24. 1180 Articles 26 Derusso AL, Fan D, Gupta J, Shelest O, Costa RM, Yin HH. 28 Steinberg JR, Turner BE, Weeks BT, et al. Analysis of female Instrumental uncertainty as a determinant of behavior under enrollment and participant sex by burden of disease in US clinical interval schedules of reinforcement. Front Integr Nuerosci 2010; trials between 2000 and 2020. JAMA Netw Open 2021; 4: e2113749. 4: 17. 29 Hosking DH, Erickson SB, Van den Berg CJ, Wilson DM, 27 Gillams K, Juliebø-Jones P, Juliebø SØ, Somani BK. Gender Smith LH. The stone clinic eect in patients with idiopathic dierences in kidney stone disease (KSD): findings from a calcium urolithiasis. J Urol 1983; 130: 1115–18. systematic review. Curr Urol Rep 2021; 22: 50. --- [PDF原文](https://sci-net.xyz/storage/7932541/fda386a0bce3ef59cf828c85b76c493158ab2fb2c7bea4667b991bf1c4868a54/Prevention-of-urinary-stones-with-hydration-a-randomised-clinical-trial-of-an-adherence-intervention.pdf) DOI: 10.1016/S0140-6736(25)02637-6