Chronic Kidney Disease, Genomics, Hypertension
Conditions
Keywords
Hypertension, Chronic Kidney Disease, End Stage Renal Disease, APOL1, Genomics, Genetics, Community-engaged
Brief summary
In this genomic medicine implementation pilot project, the investigators aim to conduct a randomized trial in a network of community health centers and primary care facilities to study processes, effects and challenges of incorporating information for apolipoprotein L1 (APOL1)-attributable genetic risk for end stage kidney disease in patients of African ancestry with hypertension .
Detailed description
CKD is most commonly associated with diabetes (40%) and hypertension (28%), and affects 26 million American adults. African ancestry populations with hypertension (HTN) have 2- to 3-fold higher risk of developing CKD, and a 5-fold increased risk to progress to end stage renal disease (ESRD) when compared with whites. HTN is a risk factor for progression of CKD and for increased cardiovascular risk with CKD. Thus targeting blood pressure control as a modifiable risk factor may both reduce CVD in people with CKD and reduce progression of CKD to end stage disease. Recent discoveries demonstrate that testable alleles of the APOL1 locus on chromosome 22 have a major effect on and explain almost all of the excess risk for hypertension-associated CKD and its progression to ESRD in African ancestry populations. We will use community-engaged approaches to enroll patients of African Ancestry with HTN from a network of community health centers and primary care facilities in Harlem and the Bronx and randomize them on a 7 to 1 ratio to receive APOL1 genetic testing and EMR-enabled provider clinical decision support incorporating APOL1 genomic risk information.
Interventions
OTHERImmediate Genetic Testing
Participants will receive the APOL1 genetic test. Trained research staff will meet with participants to communicate results and lifetime ESRD risk attributable to variations in the APOL1 gene. Primary care providers will receive APOL1 genetic risk information via a best practice alert in the participant's EMR upon commencement of a patient encounter and through results filed in the participant's genetics results section of their EMR.
Sponsors
Icahn School of Medicine at Mount Sinai
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
DOUBLE (Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
* Ages18-65 * Self-identifies as Black/African American * History of hypertension * Patient at a participating site
Exclusion criteria
* History of Chronic Kidney Disease * History of Diabetes * Pregnant * Cognitively impaired/unable to provide consent * Terminally ill * Planning to leave area of study permanently during the one year study period
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Urine Protein Excretion | Baseline and 12 months | Number of participants with urine protein excretion in urine tests to assess kidney function at 12 months as compared to baseline |
| Change in Systolic Blood Pressure | Baseline and 3 months | Change in systolic blood pressure at 3 months as compared to baseline |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Change in Medication Adherence | 3 months | Participant surveys (self-report) regarding medication adherence behaviors 3 months after randomization |
| Number of Patients With Changes in Psychosocial Behaviors | 3 months | Number of patients with changes in psychosocial behaviors 3 months after randomization |
| Number of Participants With Attitude Towards Genetic Testing | 3 months | Patient attitude towards genetic testing 3 months after randomization |
Countries
United States
Participant flow
Recruitment details
Patients were recruited from 15 academic, community and safety-net practices in New York City. 2052 participants were enrolled. however 2 participants were not randomized.
Participants by arm
| Arm | Count |
|---|---|
| Control- Delayed Testing Participants randomized to control will not receive the APOL1 genetic test upon study enrollment. They will be offered the option to take the test during their final follow-up study visit (12 months post enrollment). | 255 |
| Immediate Genetic Testing Participants randomized to intervention will receive the APOL1 genetic test immediately upon study enrollment. | 1,795 |
| Total | 2,050 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 235 | 42 |
| Overall Study | Withdrawal by Subject | 20 | 1 |
Baseline characteristics
| Characteristic | Control- Delayed Testing | Total | Immediate Genetic Testing |
|---|---|---|---|
| Age, Continuous | 53 years STANDARD_DEVIATION 10 | 53 years STANDARD_DEVIATION 10 | 53 years STANDARD_DEVIATION 10 |
| Baseline mean Systolic Blood Pressure | 133.8 mmHg STANDARD_DEVIATION 19.4 | 134.1 mmHg STANDARD_DEVIATION 19.5 | 134.2 mmHg STANDARD_DEVIATION 19.6 |
| Body mass index | 33.9 kg/m^2 STANDARD_DEVIATION 7.7 | 32.5 kg/m^2 STANDARD_DEVIATION 7.6 | 32.4 kg/m^2 STANDARD_DEVIATION 7.7 |
| Charlson Comorbidity Index 0 | 141 Participants | 1065 Participants | 924 Participants |
| Charlson Comorbidity Index 1 | 61 Participants | 542 Participants | 481 Participants |
| Charlson Comorbidity Index ≥2 | 53 Participants | 443 Participants | 390 Participants |
| Education more than some college | 162 Participants | 1170 Participants | 1008 Participants |
| Excellent/Very good self-reported Health | 64 Participants | 529 Participants | 465 Participants |
| Household income <$30,000/year | 126 Participants | 1014 Participants | 888 Participants |
| Married/Partner | 72 Participants | 612 Participants | 540 Participants |
| Number of Participants with High health literacy | 169 Participants | 1279 Participants | 1110 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 255 Participants | 2050 Participants | 1795 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 | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Female | 172 Participants | 1359 Participants | 1187 Participants |
| Sex: Female, Male Male | 83 Participants | 691 Participants | 608 Participants |
| Type of Insurance Medicaid | 109 Participants | 930 Participants | 821 Participants |
| Type of Insurance Medicare | 14 Participants | 140 Participants | 126 Participants |
| Type of Insurance None | 6 Participants | 56 Participants | 50 Participants |
| Type of Insurance Other | 8 Participants | 59 Participants | 51 Participants |
| Type of Insurance Private | 118 Participants | 863 Participants | 745 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 255 | 0 / 1,561 | 0 / 234 |
| other Total, other adverse events | 0 / 255 | 0 / 1,561 | 0 / 234 |
| serious Total, serious adverse events | 0 / 255 | 0 / 1,561 | 0 / 234 |
Outcome results
Primary
Change in Systolic Blood Pressure
Change in systolic blood pressure at 3 months as compared to baseline
Time frame: Baseline and 3 months
Population: Results available for those participants who returned for 3 month visit and had both timepoint data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Control- Delayed Testing | Change in Systolic Blood Pressure | -3 mmHg | Standard Deviation 18 |
| Immediate Genetic Testing for APOL1 Negative | Change in Systolic Blood Pressure | -3 mmHg | Standard Deviation 16 |
| Immediate Genetic Testing for APOL1 Positive | Change in Systolic Blood Pressure | -6 mmHg | Standard Deviation 18 |
Primary
Number of Participants With Urine Protein Excretion
Number of participants with urine protein excretion in urine tests to assess kidney function at 12 months as compared to baseline
Time frame: Baseline and 12 months
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Control- Delayed Testing | Number of Participants With Urine Protein Excretion | Kidney function urine test before randomization | 33 Participants |
| Control- Delayed Testing | Number of Participants With Urine Protein Excretion | Kidney function urine test after randomization | 50 Participants |
| Immediate Genetic Testing for APOL1 Negative | Number of Participants With Urine Protein Excretion | Kidney function urine test before randomization | 278 Participants |
| Immediate Genetic Testing for APOL1 Negative | Number of Participants With Urine Protein Excretion | Kidney function urine test after randomization | 377 Participants |
| Immediate Genetic Testing for APOL1 Positive | Number of Participants With Urine Protein Excretion | Kidney function urine test before randomization | 39 Participants |
| Immediate Genetic Testing for APOL1 Positive | Number of Participants With Urine Protein Excretion | Kidney function urine test after randomization | 68 Participants |
Secondary
Number of Participants With Attitude Towards Genetic Testing
Patient attitude towards genetic testing 3 months after randomization
Time frame: 3 months
Population: Survey only for participants who received genetic testing.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Control- Delayed Testing | Number of Participants With Attitude Towards Genetic Testing | Had enough information on getting the test | 1425 Participants |
| Control- Delayed Testing | Number of Participants With Attitude Towards Genetic Testing | Information for test was easy to understand | 1391 Participants |
| Control- Delayed Testing | Number of Participants With Attitude Towards Genetic Testing | Would get tested again | 1420 Participants |
| Immediate Genetic Testing for APOL1 Negative | Number of Participants With Attitude Towards Genetic Testing | Had enough information on getting the test | 208 Participants |
| Immediate Genetic Testing for APOL1 Negative | Number of Participants With Attitude Towards Genetic Testing | Information for test was easy to understand | 203 Participants |
| Immediate Genetic Testing for APOL1 Negative | Number of Participants With Attitude Towards Genetic Testing | Would get tested again | 211 Participants |
Secondary
Number of Participants With Change in Medication Adherence
Participant surveys (self-report) regarding medication adherence behaviors 3 months after randomization
Time frame: 3 months
Population: Survey only for participants who received genetic testing.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Control- Delayed Testing | Number of Participants With Change in Medication Adherence | Changed how you take BP meds | 146 Participants |
| Control- Delayed Testing | Number of Participants With Change in Medication Adherence | Take BP meds more often | 68 Participants |
| Immediate Genetic Testing for APOL1 Negative | Number of Participants With Change in Medication Adherence | Changed how you take BP meds | 53 Participants |
| Immediate Genetic Testing for APOL1 Negative | Number of Participants With Change in Medication Adherence | Take BP meds more often | 21 Participants |
Secondary
Number of Patients With Changes in Psychosocial Behaviors
Number of patients with changes in psychosocial behaviors 3 months after randomization
Time frame: 3 months
Population: Survey only for participants who received genetic testing.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Control- Delayed Testing | Number of Patients With Changes in Psychosocial Behaviors | 547 Participants |
| Immediate Genetic Testing for APOL1 Negative | Number of Patients With Changes in Psychosocial Behaviors | 129 Participants |