Idiopathic Nephrotic Syndrome
Conditions
Keywords
Pediatrics, mHealth, Behavioral intervention
Brief summary
Idiopathic nephrotic syndrome is one of the most common chronic kidney diseases in children. Patients suffer from frequent disease relapses and complications. Self-management is difficult for families and nonadherence is common, with adverse effects on the children's health. UrApp is a mobile application designed to assist families with nephrotic syndrome management. This study will examine whether providing the children's caregivers (or adolescent patients) with UrApp improves self-management and disease outcomes. This study will include 60 caregivers of children with newly diagnosed nephrotic syndrome. Participants will be randomized 1:1 to UrApp or standard of care and followed for 1 year.
Detailed description
Idiopathic nephrotic syndrome (NS) is one of the most common chronic kidney diseases in children, with a prevalence of approximately 16 cases per 100,000 children. NS is characterized by heavy urinary losses of protein leading to hypoalbuminemia, edema, and hyperlipidemia. Children are treated with high-dose corticosteroids on presentation, and \>80% respond to treatment with resolution of proteinuria and symptoms. However, 80-90% of the children initially sensitive to corticosteroids will experience disease relapse, with more than half relapsing frequently or becoming dependent on corticosteroids to maintain remission. During a relapse, patients can suffer from anasarca, acute kidney injury, serious infections, or thromboembolic events. Management of children with NS entails long-term outpatient surveillance and treatment. Home care includes the important standard-of-care task of urine monitoring to follow the relapsing-remitting nature of the disease. New proteinuria signals disease relapse before the development of overt symptoms such as edema. Thus, patients are instructed to alert their providers to the occurrence of proteinuria in a timely manner so that corticosteroids can be initiated or adjusted to treat each relapse and prevent acute disease complications. It is also important for the patients to track urine protein for resolution so that corticosteroids can be stopped or reduced to minimize steroid toxicity. Not unlike other chronic, relapsing-remitting pediatric disorders, self-management is difficult for NS patients and their caregivers. Mobile health (mHealth) is a promising, rapidly growing field in disease management. In NS, there are numerous aspects of self-management that may be facilitated by a mobile app. First, the visual analysis of a urine test strip is subject to human error, including reading the wrong reagent block and erroneous assessments of color. This can be improved through using a smartphone's camera and computer to read and analyze test strip results. Second, caregivers must remember to check their child's urine, recall results, and understand what the results mean: the demands are taxing in that disease relapse is defined as urine protein ≥2+ for 3 consecutive days and remission is defined as negative/trace urine protein for 3 consecutive days. Apps, with their inherent interactivity, can provide reminders for urine testing, capture the results, and analyze trends to detect disease relapse/remission. Apps can alert a caregiver to seek medical attention and directly transmit test results to providers. Lastly, apps can provide medication reminders for NS patients, who are on highly complex medication regimens. UrApp was iteratively developed by an expert panel of two pediatric nephrologists and three research engineers with expertise in human-computer interaction. App features were devised by the clinicians to support elements of chronic care management according to the Chronic Care Model and tasks that are challenging for caregivers. This study will include 60 caregivers of children with newly diagnosed nephrotic syndrome. Participants will be randomized 1:1 to UrApp or standard of care and followed for 1 year. In addition to the study outcome measures, user feedback will be collected via survey, interview, and by stakeholder meetings to inform app refinement.
Interventions
BEHAVIORALStandard of Care
Participants will be provided a folder of educational material on NS, including general information on symptoms, treatments, and possible complications; healthy diet for children taking corticosteroids; and low sodium diet. Site research staff will demonstrate how to check urine for protein with test strips, and educate patients on the definitions of disease relapse and remission. Urine test strips and urine protein logs will be provided to ensure that each participant can check their urine daily for protein. Participants will be instructed to check their urine daily for protein and call their provider within 1 business day for relapses and remissions.
BEHAVIORALUrApp
Caregivers/parents will download UrApp at the baseline visit. UrApp contains instructional videos to guide users. The telephone number of the patient's provider will be entered into UrApp and participants will be able to call their providers directly through UrApp. The email address of the Emory study staff will also be entered. UrApp will automatically e-mail test results to the research staff when elected by the users. Participants will be asked by study staff, and reminded by the app, to call their providers and send urine testing results to the study staff whenever there is a relapse or remission. When the study staff receives alerts of a relapse/remission via UrApp, the information will be communicated to the treating physician within 1 business day.
Sponsors
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Emory University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Caregivers of patients ages 1-17 with steroid sensitive nephrotic syndrome (clinical diagnosis with edema, nephrotic range proteinuria \[urine protein to creatinine ratio \>2 mg/mg, or ≥ 300 mg/dL or ≥ 3+ protein on urine dipstick\], and hypoalbuminemia ≤ 2.5 g/dL; resolution of proteinuria \[negative/trace protein on urine dipstick\] within 4 weeks of corticosteroid treatment) * Caregivers of pediatric patients with steroid sensitive nephrotic syndrome diagnosed within 42 days at the time of enrollment * Access to internet/wireless fidelity (Wi-Fi) in the home * Caregiver proficiency with the English language
Exclusion criteria
* Caregivers of pediatric patients with end-stage kidney disease * Caregivers of pediatric patients with renal transplantation * Caregivers of pediatric patients with clinical or histologic evidence of secondary nephrotic syndrome (e.g., systemic lupus erythematosus)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Reporting Medication Adherence | Baseline, Month 6, Month 12 | Adherence to medications is evaluated via caregiver survey with the validated 4-question Morisky, Green, and Levine (MGL) Adherence Scale. Response options are Yes (0) or No (1) and total scores range from 0 to 4 with higher scores indicating better medication adherence. Adherence will be defined as a score of ≥3 on the MGL scale. |
| Number of Participants Reporting Adherence With Urine Monitoring | Baseline, Month 6, Month 12 | Caregiver adherence with urine protein monitoring is assessed by asking caregivers on average how often they checked their child's urine for protein over the past month. Possible responses are once a week, 2-4 times a week or 5-7 times a week. Adherence is defined as checking urine at least 2 times per week. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Patient-Reported Outcomes Measurement Information System - Pediatric Quality of Life Inventory (PedsQL) Score for Pediatric Patients | Baseline, Month 6, Month 12 | The 23-item PedsQL was developed as part of the NIH Roadmap Initiative to create universal measures for patient-reported outcomes, and contains questions in the domains of social-peer, depression, anxiety, mobility, and function. Responses are given on a 5-point scale where 0 = never and 4 = almost always. Items are reverse scored and linearly transformed to a scale of 0 to 100, where higher total mean scores indicate a better quality of life. |
| Caregiver Self-efficacy Score | Baseline, Month 6, Month 12 | Self-efficacy of caregivers for managing nephrotic syndrome of pediatric patients is assessed with a 3-item instrument adapted from the Chronic Disease Self-Efficacy Scales. Responses are given on a 10-point scale where 0 = not confident at all and 10 = totally confident. Total scores range from 0 to 30 with higher scores indicating increased self-efficacy. |
| Number of Hospitalizations Among Pediatric Patients | Month 6, Month 12 | Medical records were reviewed for the primary reason for admission and NS disease complications, such as bacterial peritonitis, septicemia, shock, blood clot(s), acute kidney injury, and seizures from hyponatremia or hypertension. |
| Number Pediatric Patients With Delayed Detection of Relapses | Month 6, Month 12 | Relapses detected only after patients experienced symptoms of relapse, indicating delayed detection, is compared between study arms. Patient medical charts were reviewed for occurrence and frequency of delayed relapse reporting which is defined as a relapse that was not reported to the treating physician until clinical manifestations or complications occurred and/or only discovered during planned or unplanned visits or hospitalizations. |
| Patient-Reported Outcomes Measurement Information System - Pediatric Quality of Life Inventory (PedsQL) Score for Parents | Baseline, Month 6, Month 12 | The 23-item PedsQL was developed as part of the NIH Roadmap Initiative to create universal measures for patient-reported outcomes and contains questions in the domains of social-peer, depression, anxiety, mobility, and function. Responses are given on a 5-point scale where 0 = never and 4 = almost always. Items are reverse scored and linearly transformed to a scale of 0 to 100, where higher total mean scores indicate a better quality of life. |
Countries
United States
Participant flow
Recruitment details
Caregiver participants were recruited from Children's Healthcare of Atlanta, in Atlanta, Georgia, Oregon Health and Science University, in Portland, Oregon, and the University of Minnesota Children's Hospital in Minneapolis, Minnesota, USA. Participant enrollment began September 17, 2019, and all follow-up assessments were completed by April 25, 2025.
Pre-assignment details
Caregivers of pediatric patients were enrolled into the study, randomized to a study arm, and took part in the study intervention. Data for outcome measures and adverse events were collected about and from pediatric patients but the study participants are the caregivers rather than pediatric patients.
Participants by arm
| Arm | Count |
|---|---|
| UrApp Caregiver participants randomized to this study arm use the UrApp mobile application for one year, in addition to receiving the standard of care.
UrApp: Caregivers/parents download UrApp at the baseline visit. UrApp contains instructional videos to guide users. The telephone number of the patient's provider is entered into UrApp and participants are able to call their providers directly through UrApp. The email address of the Emory study staff is also entered. UrApp automatically e-mails test results to the research staff when elected by the users. Participants are asked by study staff, and reminded by the app, to call their providers and send urine testing results to the study staff whenever there is a relapse or remission. When the study staff receives alerts of a relapse/remission via UrApp, the information is communicated to the treating physician within 1 business day. | 30 |
| Standard of Care Caregiver participants randomized to this study arm receive the standard of care for one year.
Standard of Care: Participants are provided a folder of educational material on nephrotic syndrome (NS), including general information on symptoms, treatments, and possible complications; healthy diet for children taking corticosteroids; and low sodium diet. Site research staff demonstrate how to check urine for protein with test strips and educate patients on the definitions of disease relapse and remission. Urine test strips and urine protein logs are provided to ensure that each participant can check their urine daily for protein. Participants are instructed to check their urine daily for protein and call their provider within 1 business day for relapses and remissions. | 28 |
| Total | 58 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 5 | 5 |
Baseline characteristics
| Characteristic | UrApp | Standard of Care | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 30 Participants | 28 Participants | 58 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants | 4 Participants | 7 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 27 Participants | 24 Participants | 51 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 6 Participants | 2 Participants | 8 Participants |
| Race (NIH/OMB) Black or African American | 5 Participants | 7 Participants | 12 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 3 Participants | 4 Participants |
| Race (NIH/OMB) White | 18 Participants | 16 Participants | 34 Participants |
| Region of Enrollment United States | 30 Participants | 28 Participants | 58 Participants |
| Sex: Female, Male Female | 11 Participants | 9 Participants | 20 Participants |
| Sex: Female, Male Male | 19 Participants | 19 Participants | 38 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 30 | 0 / 28 |
| other Total, other adverse events | 0 / 0 | 0 / 0 |
| serious Total, serious adverse events | 5 / 30 | 9 / 28 |
Outcome results
Primary
Number of Participants Reporting Adherence With Urine Monitoring
Caregiver adherence with urine protein monitoring is assessed by asking caregivers on average how often they checked their child's urine for protein over the past month. Possible responses are once a week, 2-4 times a week or 5-7 times a week. Adherence is defined as checking urine at least 2 times per week.
Time frame: Baseline, Month 6, Month 12
Population: This analysis includes participants who completed the study and responded to this survey. Survey data are missing for some participants. If a participant missed a study visit they were sent the survey electronically but some participants did not complete every survey.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| UrApp | Number of Participants Reporting Adherence With Urine Monitoring | Adherence at Baseline | 21 Participants |
| UrApp | Number of Participants Reporting Adherence With Urine Monitoring | Adherence at Month 6 | 19 Participants |
| UrApp | Number of Participants Reporting Adherence With Urine Monitoring | Adherence at Month 12 | 14 Participants |
| Standard of Care | Number of Participants Reporting Adherence With Urine Monitoring | Adherence at Baseline | 18 Participants |
| Standard of Care | Number of Participants Reporting Adherence With Urine Monitoring | Adherence at Month 6 | 18 Participants |
| Standard of Care | Number of Participants Reporting Adherence With Urine Monitoring | Adherence at Month 12 | 14 Participants |
Primary
Number of Participants Reporting Medication Adherence
Adherence to medications is evaluated via caregiver survey with the validated 4-question Morisky, Green, and Levine (MGL) Adherence Scale. Response options are Yes (0) or No (1) and total scores range from 0 to 4 with higher scores indicating better medication adherence. Adherence will be defined as a score of ≥3 on the MGL scale.
Time frame: Baseline, Month 6, Month 12
Population: This analysis includes participants who completed the study and responded to this survey. Survey data are missing for some participants. If a participant missed a study visit they were sent the survey electronically but some participants did not complete every survey.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| UrApp | Number of Participants Reporting Medication Adherence | Participants with score ≥3 at Baseline | 25 Participants |
| UrApp | Number of Participants Reporting Medication Adherence | Participants with score ≥3 at Month 6 | 19 Participants |
| UrApp | Number of Participants Reporting Medication Adherence | Participants with score ≥3 at Month 12 | 15 Participants |
| Standard of Care | Number of Participants Reporting Medication Adherence | Participants with score ≥3 at Baseline | 21 Participants |
| Standard of Care | Number of Participants Reporting Medication Adherence | Participants with score ≥3 at Month 6 | 18 Participants |
| Standard of Care | Number of Participants Reporting Medication Adherence | Participants with score ≥3 at Month 12 | 16 Participants |
Secondary
Caregiver Self-efficacy Score
Self-efficacy of caregivers for managing nephrotic syndrome of pediatric patients is assessed with a 3-item instrument adapted from the Chronic Disease Self-Efficacy Scales. Responses are given on a 10-point scale where 0 = not confident at all and 10 = totally confident. Total scores range from 0 to 30 with higher scores indicating increased self-efficacy.
Time frame: Baseline, Month 6, Month 12
Population: This analysis includes participants who completed the study and responded to this survey. Survey data are missing for some participants. If a participant missed a study visit they were sent the survey electronically but some participants did not complete every survey.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| UrApp | Caregiver Self-efficacy Score | Month 6 | 9.65 score on a scale | Standard Deviation 1.26 |
| UrApp | Caregiver Self-efficacy Score | Baseline | 8.97 score on a scale | Standard Deviation 1.84 |
| UrApp | Caregiver Self-efficacy Score | Month 12 | 9.21 score on a scale | Standard Deviation 1.51 |
| Standard of Care | Caregiver Self-efficacy Score | Baseline | 9.35 score on a scale | Standard Deviation 1.26 |
| Standard of Care | Caregiver Self-efficacy Score | Month 6 | 9.42 score on a scale | Standard Deviation 0.81 |
| Standard of Care | Caregiver Self-efficacy Score | Month 12 | 9.49 score on a scale | Standard Deviation 0.88 |
Secondary
Number of Hospitalizations Among Pediatric Patients
Medical records were reviewed for the primary reason for admission and NS disease complications, such as bacterial peritonitis, septicemia, shock, blood clot(s), acute kidney injury, and seizures from hyponatremia or hypertension.
Time frame: Month 6, Month 12
Population: Information for this outcome measure was collected from medical records. Some participants did not attend clinic visits corresponding with the time frames of this study. The overall number of participants analyzed reflects caregiver participants who contributed data at either the 6 month or 12 month time points, while the number of participants analyzed at each time point are pediatric patients who had medical record data to be reviewed for the indicated study time point.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| UrApp | Number of Hospitalizations Among Pediatric Patients | Month 6 | 3 count of hospitalizations |
| UrApp | Number of Hospitalizations Among Pediatric Patients | Month 12 | 4 count of hospitalizations |
| Standard of Care | Number of Hospitalizations Among Pediatric Patients | Month 6 | 7 count of hospitalizations |
| Standard of Care | Number of Hospitalizations Among Pediatric Patients | Month 12 | 10 count of hospitalizations |
Secondary
Number Pediatric Patients With Delayed Detection of Relapses
Relapses detected only after patients experienced symptoms of relapse, indicating delayed detection, is compared between study arms. Patient medical charts were reviewed for occurrence and frequency of delayed relapse reporting which is defined as a relapse that was not reported to the treating physician until clinical manifestations or complications occurred and/or only discovered during planned or unplanned visits or hospitalizations.
Time frame: Month 6, Month 12
Population: Information for this outcome measure was collected from medical records. Some participants did not attend clinic visits corresponding with the time frames of this study. The overall number of participants analyzed reflects caregiver participants who contributed data at either the 6 month or 12 month time points, while the number of participants analyzed at each time point are pediatric patients who had a least one relapse during the time frame.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| UrApp | Number Pediatric Patients With Delayed Detection of Relapses | Month 6 | 2 Participants |
| UrApp | Number Pediatric Patients With Delayed Detection of Relapses | Month 12 | 1 Participants |
| Standard of Care | Number Pediatric Patients With Delayed Detection of Relapses | Month 6 | 7 Participants |
| Standard of Care | Number Pediatric Patients With Delayed Detection of Relapses | Month 12 | 4 Participants |
Secondary
Patient-Reported Outcomes Measurement Information System - Pediatric Quality of Life Inventory (PedsQL) Score for Parents
The 23-item PedsQL was developed as part of the NIH Roadmap Initiative to create universal measures for patient-reported outcomes and contains questions in the domains of social-peer, depression, anxiety, mobility, and function. Responses are given on a 5-point scale where 0 = never and 4 = almost always. Items are reverse scored and linearly transformed to a scale of 0 to 100, where higher total mean scores indicate a better quality of life.
Time frame: Baseline, Month 6, Month 12
Population: This analysis includes participants who completed the study and responded to this survey. Survey data are missing for some participants. If a participant missed a study visit they were sent the survey electronically but some participants did not complete every survey.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| UrApp | Patient-Reported Outcomes Measurement Information System - Pediatric Quality of Life Inventory (PedsQL) Score for Parents | Baseline | 83 score on a scale | Standard Deviation 16 |
| UrApp | Patient-Reported Outcomes Measurement Information System - Pediatric Quality of Life Inventory (PedsQL) Score for Parents | Month 6 | 86 score on a scale | Standard Deviation 18 |
| UrApp | Patient-Reported Outcomes Measurement Information System - Pediatric Quality of Life Inventory (PedsQL) Score for Parents | Month 12 | 88 score on a scale | Standard Deviation 13 |
| Standard of Care | Patient-Reported Outcomes Measurement Information System - Pediatric Quality of Life Inventory (PedsQL) Score for Parents | Baseline | 85 score on a scale | Standard Deviation 12 |
| Standard of Care | Patient-Reported Outcomes Measurement Information System - Pediatric Quality of Life Inventory (PedsQL) Score for Parents | Month 6 | 84 score on a scale | Standard Deviation 14 |
| Standard of Care | Patient-Reported Outcomes Measurement Information System - Pediatric Quality of Life Inventory (PedsQL) Score for Parents | Month 12 | 76 score on a scale | Standard Deviation 17 |
Secondary
Patient-Reported Outcomes Measurement Information System - Pediatric Quality of Life Inventory (PedsQL) Score for Pediatric Patients
The 23-item PedsQL was developed as part of the NIH Roadmap Initiative to create universal measures for patient-reported outcomes, and contains questions in the domains of social-peer, depression, anxiety, mobility, and function. Responses are given on a 5-point scale where 0 = never and 4 = almost always. Items are reverse scored and linearly transformed to a scale of 0 to 100, where higher total mean scores indicate a better quality of life.
Time frame: Baseline, Month 6, Month 12
Population: This analysis includes pediatric patients who completed the study and responded to this survey. Survey data are missing for some pediatric patients. If a caregiver participant missed a study visit they were sent the survey electronically but some pediatric patients did not complete this survey.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| UrApp | Patient-Reported Outcomes Measurement Information System - Pediatric Quality of Life Inventory (PedsQL) Score for Pediatric Patients | Baseline | 91 score on a scale | Standard Deviation 7 |
| UrApp | Patient-Reported Outcomes Measurement Information System - Pediatric Quality of Life Inventory (PedsQL) Score for Pediatric Patients | Month 6 | 89 score on a scale | Standard Deviation 10 |
| UrApp | Patient-Reported Outcomes Measurement Information System - Pediatric Quality of Life Inventory (PedsQL) Score for Pediatric Patients | Month 12 | 94 score on a scale | Standard Deviation 5 |
| Standard of Care | Patient-Reported Outcomes Measurement Information System - Pediatric Quality of Life Inventory (PedsQL) Score for Pediatric Patients | Baseline | 83 score on a scale | Standard Deviation 15 |
| Standard of Care | Patient-Reported Outcomes Measurement Information System - Pediatric Quality of Life Inventory (PedsQL) Score for Pediatric Patients | Month 6 | 84 score on a scale | Standard Deviation 7 |
| Standard of Care | Patient-Reported Outcomes Measurement Information System - Pediatric Quality of Life Inventory (PedsQL) Score for Pediatric Patients | Month 12 | 81 score on a scale | Standard Deviation 14 |