This study was an individual-level, randomized trial that included 999 patients at 55 primary care clinic sites in the Geisinger Health System, a large integrated health system in rural Pennsylvania. Funding was provided by the National Kidney Foundation (NKF), and the Geisinger Institutional Review Board approved the protocol (2017–0516). Health care providers and pharmacists across the system received education about management of proteinuria as well as information about the research study in small group lectures.
Study population
We used electronic health record data to identify eligible patients with hypertension who had never undergone proteinuria screening by any method. Inclusion criteria included Geisinger primary care patients ≥18 years of age with a hypertension diagnosis, blood pressure ≥ 130/80 mmHg at last outpatient visit, and active patient portal use with a listed phone number and email address. Main exclusion criteria included diabetes, end-stage renal disease, and estimated glomerular filtration rate (eGFR) < 15 ml/min/1.73 m2.
Participant flow and intervention
A total of 999 patients met the inclusion/exclusion criteria and received a mailed reminder to complete proteinuria screening, a National Kidney Foundation educational booklet about the importance of proteinuria screening, and a standing Geisinger lab urinalysis order March 19–21, 2018. Since proteinuria screening is standard-of-care for patients with hypertension, informed consent was not required for this initial contact. A computer program was then used to randomize patients 1:1 to the intervention or control arm, stratified by baseline eGFR < 60 ml/min/1.73m2 since CKD is also an indication for proteinuria screening.
Patients in the control arm received no intervention, whereas patients in the intervention arm received a notification letter about the home urine smartphone test approximately 2 weeks later, with an option to opt-out of further contact by the research team. This was followed by telephone calls by the Geisinger Survey unit, who made up to 7 attempts and left up to 3 voicemails. We also conducted weekly data pulls to identify and remove any patients from the call list who had already completed proteinuria screening at the Geisinger lab. Patients who provided consent were sent a text message link to download the dip.io app from the Apple Store or Google Play (Fig. 1). The testing kit, along with a project leaflet, were shipped by Healthy.io using a third-party fulfillment service. If participants had not completed the test within the next week, Healthy.io’s call center contacted participants to validate receipt of kit and application and trouble-shoot any issues that may have prevented the participants from completing the test.
The dip.io test consists of a home test kit and a smartphone application. The kit consists of a standard 10 parameter urinalysis dipstick, a custom designed urine cup and a color-board, which enables accurate analysis in different lighting environments. To conduct the test, patients open the app, follow directions provided on-screen, collect urine in the provided container, dip the urinalysis dipstick (Acon Mission), place the dipstick on the color board, and then scan the dipstick and color board using the app. For this project, results were transmitted to a Health Insurance Portability and Accountability Act (HIPAA)-compliant website portal, which was accessed by the research team. The study team contacted patients with abnormal home test results, and ordered confirmation ACR testing for trace or greater urine protein on urinalysis, or repeat urinalysis testing at a Geisinger laboratory for other urinalysis abnormalities along with notification to the PCP. For patients with detected albuminuria, the study team sent a notification to the PCP with the following guideline-based recommendations: treat to office blood pressure < 130/80 mmHg, treat with ACEI or ARB and statin. Providers had the option of referral for further management by pharmacists, who received training in management of albuminuria and hypertension. PCPs were blinded to their patients’ assignment with the exception that if an abnormal home test resulted, PCPs were later informed of the result. Final outcome data was assessed by a blinded member of the research team (JL).
Outcomes
Co-primary outcomes were completion of proteinuria screening by any method and number of quantified albuminuria cases (ACR ≥ 30 mg/g or protein/creatinine ratio ≥ 150 mg/g) at the end of 3 months (6/20/18). An exploratory outcome examined was the number of patients with trace or 1+ urine protein tests at the end of 3 months.
Analytic considerations
With a sample size of 1000 total patients enrolled in the trial and assumptions of albuminuria prevalence of 20% [14], screening compliance rates of 40% in the intervention group and 10% in the control group, we estimated that we would have > 90% power to detect a difference in screening compliance between groups, and > 90% power to detect a difference in detected number of albuminuria cases.
We conducted intention-to-treat analyses and used logistic regression to examine the effects of the intervention on screening outcomes. Satisfaction with the home test was evaluated by a survey administered by smartphone after test completion. P values < 0.05 were considered statistically significant without correction for multiple comparisons, and analyses were completed using STATA version 15.1.