Prevention of Urinary Stones With Hydration (PUSH)

A randomized clinical trial to investigate the impact of increased fluid intake and increased urine output on the recurrence rate of urinary stone disease (USD) in adults and children. The primary aim of the trial is to determine whether a multi-component program of behavioral interventions to increase fluid intake will result in reduced risk of stone disease progression over a 2-year period.

Study Overview

• Status: Completed
• Conditions: Urinary Stones
• Intervention / Treatment: Behavioral: Fluid prescription; Behavioral: Financial incentive; Behavioral: Structured Problem Solving

Detailed Description

This is a two arm randomized controlled trial that incorporates pragmatic features, an adaptable intervention, patient choice, and remote monitoring of fluid intake through a "smart" water bottle. The study period is 24 months and will enroll approximately 1642 participants. Randomization will be stratified within a study site by age (adult vs. adolescent) and first time vs. recurrent stone former.

Intervention and control arm study participants will receive a smart water bottle that records daily fluid consumption, usual care including guideline-based recommendations of adequate fluid intake to decrease kidney stone recurrence, and periodic 24 hour urine collections, imaging (low-dose CT scan or ultrasound) and follow-up questionnaires.

• Study Type: Interventional
• Enrollment (Actual): 1658
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University, St. Louis
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19146
      • Children's Hospital of Philadelphia
  • Texas
    • Dallas, Texas, United States, 75390
      • University of Texas Southwestern
    • Dallas, Texas, United States, 75390
      • Children's Hospital
  • Washington
    • Seattle, Washington, United States, 98195
      • University of Washington

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Aged ≥ 12 years

2. At least 1 symptomatic stone event (passage or procedural intervention) within 3 years prior to enrollment or a symptomatic stone event within 5 years if the patient also has new stone formation detected on imaging during the last 5 years. Symptomatic stone defined as any of the following:

   1. Stone passage
   2. Procedural intervention
   3. Radiographically or ultrasonographically confirmed stone with any of the following:

   i. Gross hematuria ii. Renal colic or atypical abdominal pain attributed to the stone, as determined by a treating provider iii. A clinical pattern of intermittent symptoms consistent with intermittent obstruction at the ureteropelvic junction, as determined by a treating provider

3. Low 24-hr urine volume

   1. ≥18 years old: <2.0 L/day
   2. <18 years old: <25 ml/Kg/day up to 2.0L/day
4. Able to provide informed consent (parental permission for children)
5. Owning and willing to use a smartphone or other device (e.g., tablet) compatible with the study-provided wireless enabled "smart" bottle

Exclusion Criteria:

1. Spinal cord injury
2. Currently undergoing active treatment for cancer except basal cell skin cancer, or patients with a history of cancer who completed their initial therapy <1 year before screening.

3. Known infectious (struvite), monogenic or other causes of stone disease for which therapies are likely to significantly alter course of stone disease

   1. Cystinuria
   2. Primary hyperoxaluria
   3. Primary xanthinuria
   4. Primary hyperparathyroidism
   5. Sarcoidosis
   6. Medullary sponge kidney
4. History or presence of hyponatremia (serum sodium <130 mmol/L) or hypo-osmolality (serum osmolality <275 mosm/kg)

5. Study participants with comorbidities that preclude high fluid intake or prior surgery precluding high fluid intake or leading to GI fluid losses

   1. History of or current Crohn's disease, ulcerative colitis, short gut syndrome (e.g. ileostomy, bowel bypass surgery to treat obesity, small bowel resection), chronic diarrhea, or GI tract ostomy.
   2. History of malabsorptive (e.g., Roux-en-Y gastric bypass) or restrictive (e.g., sleeve gastrectomy) bariatric surgery procedures
   3. Congestive heart failure

   i. NYHA class II or greater, and/or ii. Hospital admission in the past year for heart failure d. Lung disease with a home oxygen requirement e. Chronic kidney disease (eGFR <30 ml/min/1.7 m2 over a 3-month period) i. For adults (age ≥18), we will use the CKD-Epi equation which requires the measurement of serum creatinine only. ii. For children (age <18), we will use the bedside Schwartz (CKiD) formula. f. Nephrotic syndrome (>3.5 grams of protein per 24 hours) g. Cirrhosis with ascites

6. Women who are currently pregnant or planning pregnancy within 2 years.
7. Renal transplant recipient
8. Bedridden study participants (ECOG ≥ 3)
9. Uncorrected anatomical obstruction of the urinary tract
10. History of recurrent urinary tract infections (> 3 UTI/year proven by urine culture)

11. Exclusions due to medication use:

    1. Chronic use of lithium
    2. Long-term glucocorticoid use (> 7.5 mg prednisone daily for > 30 days prior to enrollment)
    3. Intake of narcotic medication on a daily basis for >30 days prior to enrollment
    4. Supplemental Vitamin C (> 1 g daily)
12. Individuals with stones that have developed after the initiation of medications that are strongly associated with USD such as carbonic anhydrase inhibitors (acetazolamide, topiramate, zonisamide), high dose vitamin C (> 1 g daily), high dose calcium supplementation (> 1,200 mg daily) AND who have discontinued or plan to discontinue these medications.

13. Individuals with stones composed of medications that may crystallize in the urine (guaifenesin, sulfonamides, triamterene, and the protease inhibitors indinavir and nelfinavir) AND who have discontinued or plan to discontinue these medications.

    Note: Individuals who are on long-term medications that increase the risk of stone disease, who cannot stop these medications due to other chronic conditions (e.g., HIV) and who may reduce their risk for stone recurrence through increased fluid intake, will be eligible to participate in the trial. Examples of these medications include:

    1. Carbonic anhydrase inhibitors (acetazolamide, topiramate, zonisamide)
    2. Medications that may crystallize in the urine (guaifenesin, sulfonamides, triamterene, and the protease inhibitors indinavir and nelfinavir).
14. Study participants <2 yrs life expectancy
15. Non-English Speakers
16. History of Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH)
17. Anatomical urologic abnormalities including ileal conduits, horseshoe kidney, megaureter or solitary kidney.
18. Psychiatric conditions impairing compliance with the study
19. Vulnerable population (prisoner and/or cognitive impairment that the investigator feels will impact the study participant's ability to participate in the protocol)
20. Individual who will be unable to participate in the protocol in the judgment of the investigator.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intervention; Participants in the intervention arm will receive an individualized "fluid prescription", which will be the additional volume of fluid intake needed to maintain a study-specified urine output. This fluid will be consumed from and measured by a smart water bottle. The intervention arm also includes a behavioral program that consists of financial incentives and structured problem solving (SPS) to maintain the recommended fluid intake.	Behavioral: Fluid prescription; The additional amount of fluid that the participant will need to consume each day, using the smart water bottle, in order to meet the study-specified urine output. This fluid is in addition to any other sources of fluid (ex. cups of coffee, bottled sports drink) that the participant consumes each day.; Behavioral: Financial incentive; Participants in the Intervention Arm who meet their fluid intake goal on randomly selected days will receive a small payment for that day.; Behavioral: Structured Problem Solving; Structure Problem Solving involves interactions with health coaches to help participants develop feasible solutions to overcoming personal barriers to maintaining the prescribed fluid intake.
No Intervention: Control; Participants in the control arm will receive standard care instructions according to American Urological Association (AUA) guidelines to increase overall fluid consumption to achieve study-specified urine output. They will also receive a "smart" water bottle with capability to self-monitor their fluid intake.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With a Symptomatic Stone Event	Having a symptomatic stone event was defined as meeting any 1 of 2 criteria - stone passage or a procedural intervention for a stone (whether the stone was causing symptoms or not).	Baseline through approximately 24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Asymptomatic Formation of New Stone		Up to approximately 24 months
Number of Participants With Growth of Existing Stone by ≥ 2 mm in Any Dimension	Comparison of the size of any stone on first observation versus later observations or at passage. Will be measured primarily through imaging (CT scan and ultrasound).	Baseline through approximately 24 months
Number of Participants With Symptomatic Stone Recurrence, Asymptomatic Stone Formation, or Increase of Existing Stone by ≥2 mm in Any Dimension		Baseline through approximately 24 months
24-hour Urine Total Volume		6, 12, 18, and 24 months
Costs of Study Interventions and Treatments for USD During the Follow-up Period	To estimate study intervention costs, we will use a tool specifically designed to estimate costs associated with patient-centered interventions (R01NR011873). The costs of medical resource use will be assigned based on payment schedules (e.g., Medicare). To incorporate potential differences in health-related quality of life experienced by participants in the cost-effectiveness analysis, health state utilities will be estimated from existing literature. Full details of the economic analysis will be specified in the Economic Statistical Analysis Plan.	Baseline through approximately 24 months
Comprehensive Assessment of Self-Reported Urinary Symptoms (CASUS)	The CASUS is a tool used to assess lower urinary tract symptoms (LUTS) in individuals, providing a comprehensive evaluation of various urinary issues. It's designed to capture a wide range of symptoms, including storage, voiding, post-micturition, urgency, incontinence, and abnormal bladder sensations. The total score ranges from 0 to 38, where a higher score indicates greater urinary symptoms.	Baseline, 6, 12, 18, and 24 months

Collaborators and Investigators

• Sponsor: Duke University
• Collaborators: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Investigators: Principal Investigator: Charles Scales, MD, MSHS, Duke University

Publications and helpful links

General Publications

• Scales CD Jr, Desai AC, Harper JD, Lai HH, Maalouf NM, Reese PP, Tasian GE, Al-Khalidi HR, Kirkali Z, Wessells H; Urinary Stone Disease Research Network. Prevention of Urinary Stones With Hydration (PUSH): Design and Rationale of a Clinical Trial. Am J Kidney Dis. 2021 Jun;77(6):898-906.e1. doi: 10.1053/j.ajkd.2020.09.016. Epub 2020 Nov 16.

Helpful Links

• The Urinary Stone Disease Research Network (USDRN) website. The USDRN is the program conducting the PUSH study.

Study record dates

Study Major Dates

• Study Start (Actual): October 4, 2017
• Primary Completion (Actual): May 18, 2024
• Study Completion (Actual): May 31, 2024

Study Registration Dates

• First Submitted: August 2, 2017
• First Submitted That Met QC Criteria: August 8, 2017
• First Posted (Actual): August 9, 2017

Study Record Updates

• Last Update Posted (Actual): August 5, 2025
• Last Update Submitted That Met QC Criteria: July 17, 2025
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Keywords: Urinary Calculi; Kidney Stone; Urinary Stone Disease
• Additional Relevant MeSH Terms: Urogenital Diseases; Male Urogenital Diseases; Pathological Conditions, Anatomical; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Calculi; Urinary Calculi; Urolithiasis
• Other Study ID Numbers: Pro00083271; 1U01DK110988 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Data and samples, for subjects who consent to sharing, will be sent to the NIDDK Data and Biological Samples Repository following database lock.
• IPD Sharing Time Frame: 2 years after the last visit of the last participant randomized.
• IPD Sharing Access Criteria: Anyone with access to the NIDDK Data and Biological Samples Repository
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No