APOL1 Genetic Testing for Kidney Disease

Recruiting at 1 trial location

Overseen By Elisa J Gordon, PhD, MPH

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Northwestern University

Disqualifiers: Non-African ancestry, Pregnancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 61

390 Participants Needed

Trial Summary

Do I need to stop my current medications for this trial?

The trial information does not specify whether you need to stop taking your current medications. It is best to discuss this with the trial coordinators or your healthcare provider.

What data supports the effectiveness of APOL1 genetic testing for kidney disease?

Research suggests that APOL1 genetic testing can help identify individuals at higher risk for kidney disease, particularly in people of African ancestry, which may improve risk assessment and decision-making in kidney transplantation. ^{1 2 3 4 5}

Is APOL1 genetic testing safe for humans?

APOL1 genetic testing itself is generally safe, but having two APOL1 risk variants is linked to a higher risk of kidney disease, especially in people of African ancestry. This information is important for kidney donors and recipients, as it can affect kidney transplant outcomes. ^{1 2 3 4 6}

How is APOL1 genetic testing different from other treatments for kidney disease?

APOL1 genetic testing is unique because it identifies genetic variants that increase the risk of kidney disease, particularly in individuals with African ancestry, rather than treating the disease directly. This testing helps in assessing the risk and guiding decisions in kidney transplantation, unlike traditional treatments that focus on managing symptoms or slowing disease progression. ^{1 3 4 7 8}

What is the purpose of this trial?

Living donor (LD) kidney transplantation is the optimal treatment for patients with end-stage kidney disease (ESKD). However, LDs take on a higher risk of future ESKD themselves. African American (AA) LDs have an even greater, 3.3-fold, risk of ESKD than white LDs post-donation. Because evidence suggests that Apolipoprotein L1 (APOL1) risk variants contribute to this greater risk, transplant nephrologists are increasingly using APOL1 testing to evaluate LD candidates of African ancestry. However, nephrologists do not consistently perform genetic counseling with LD candidates about APOL1 due to a lack of knowledge and skill in counseling about APOL1. Without proper counseling, APOL1 testing will magnify LD candidates' decisional conflict about donating, jeopardizing their informed consent. Given their elevated risk of ESRD post-donation, and AAs' widely-held cultural concerns about genetic testing, it is ethically critical to protect AA LD candidates' safety through APOL1 testing in a culturally competent manner to improve informed decisions about donating. No transplant programs have integrated APOL1 testing into LD evaluation in a culturally competent manner. Clinical "chatbots," mobile apps that use artificial intelligence to provide genetic information to patients and relieve constraints on clinicians' time, can improve informed treatment decisions and reduce decisional conflict. The chatbot "Gia," created by a medical genetics company, can be adapted to any condition. However, no chatbot on APOL1 is currently available. No counseling training programs are available for nephrologists to counsel AA LDs about APOL1 and donation in a culturally competent manner. Given the shortage of genetic counselors, increasing nephrologists' genetic literacy is critical to integrating genetic testing into practice. The objective of this study is to culturally adapt and evaluate the effectiveness of an APOL1 testing program for AA LDs at two transplant centers serving large AA LD populations (Chicago, IL, and Washington, DC). The APOL1 testing program will evaluate the effect of the culturally competent testing, chatbot, and counseling on AA LD candidates' decisional conflict about donating, preparedness for decision-making, willingness to donate, and satisfaction with informed consent. The specific aims are to: 1. Adapt Gia and transplant counseling to APOL1 for use in routine clinical practice 2. Evaluate the effectiveness of this intervention on decisional conflict, preparedness, and willingness to donate in a pre-post design 3. Evaluate the implementation of this intervention into clinical practice by using the RE-AIM framework to longitudinally evaluate nephrologist counseling practices and LDs' satisfaction with informed consent. The impact of this study will be the creation of a model for APOL1 testing of AA LDs, which can then be implemented nationally via implementation science approaches. APOL1 will serve as a model for integrating culturally competent genetic testing into transplant and other practices to improve patient informed consent.

Research Team

Elisa J Gordon

Principal Investigator

Northwestern University

Eligibility Criteria

This trial is for cognitively intact, English-speaking adults of African descent, including a wide range of nationalities like African American/Black, Jamaican, and others who are considering becoming living kidney donors. It's not for those without African ancestry or pregnant women.

Inclusion Criteria

English-speaking

I am mentally sharp and can make decisions.

My gender does not affect my eligibility.

Exclusion Criteria

Individuals who do not identify as African American/Black and are not aware of having any biologically-related family with African ancestry and do not have African ancestry

Pregnant women cannot be living kidney donors

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Intervention

Participants in the intervention group use the chatbot for 5-7 minutes and provide a saliva sample for APOL1 genetic testing

Approximately 1 week

1 visit (in-person)

Counseling

Transplant nephrologists engage in a counseling discussion with donor candidates about APOL1 and living donation

1-2 weeks

Follow-up

Participants are monitored for decisional conflict, preparedness, willingness to donate, and satisfaction with informed consent

Approximately 8 weeks

Follow-up assessments at Day 60

Treatment Details

Interventions

• APOL1 genetic testing
• Components of Genetic Counseling
• EHR integration

Trial Overview The study tests a culturally adapted APOL1 genetic testing program with components like genetic counseling and EHR integration. It uses the 'Gia' chatbot to help potential donors understand their risks and make informed decisions about donation.

Participant Groups

Group I: Intervention Arm Experimental Treatment 3 Interventions

APOL1 testing program

Group II: Control Arm Active Control 1 Intervention

No intervention will be administered. Usual care will be administered.

APOL1 genetic testing is already approved in United States, European Union for the following indications:

Approved in United States as APOL1 genetic testing for:

• Risk assessment for kidney disease in living donors of African ancestry

Approved in European Union as APOL1 genetic testing for:

• Risk assessment for kidney disease in living donors of African or Caribbean heritage

Who Is Running the Clinical Trial?

Northwestern University

Lead Sponsor

Trials

1,674

Recruited

989,000+

Georgetown University

Collaborator

Trials

355

Recruited

142,000+

Findings from Research

Not all individuals with the high-risk APOL1 genotype develop kidney disease, indicating that other factors may influence disease progression.

The study identifies several biomarkers associated with renal outcomes in high-risk APOL1 individuals, which could enhance risk assessment and understanding of APOL1 nephropathy mechanisms in precision medicine.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

"Biomarking" the transition from genetic risk to kidney disease. Kruzel-Davila, E., Skorecki, K.[2022]

About 13% of individuals of African ancestry carry two copies of the APOL1 gene variant, which is linked to a higher risk of end-stage renal disease (ESRD), raising concerns for kidney transplantation outcomes.

Current evidence suggests that kidneys from donors with two APOL1 risk alleles may have poorer survival rates compared to those from donors with fewer risk alleles, prompting discussions on how to incorporate APOL1 testing into clinical practices despite insufficient data for formal guidelines.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Integrating APOL1 Gene Variants Into Renal Transplantation: Considerations Arising From the American Society of Transplantation Expert Conference. Newell, KA., Formica, RN., Gill, JS., et al.[2023]

Approximately half of the transplant centers in the U.S. offer ApoL1 testing for potential kidney donors, but there is significant variability in how these centers approach the testing process and engage with donors.

Only 50% of centers that conduct ApoL1 testing involve donors in decision-making when they test positive for 2 risk variants, highlighting a need for improved communication and guidelines to build trust and address concerns among black living donors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Variation of ApoL1 Testing Practices for Living Kidney Donors. McIntosh, T., Mohan, S., Sawinski, D., et al.[2022]

Kidneys transplanted from African American donors with two APOL1 nephropathy risk variants have a significantly shorter graft survival, with a hazard ratio of 3.84, indicating a higher risk of failure compared to those with fewer or no risk variants.

The study suggests that genotyping for APOL1 risk variants in kidney donors could enhance donor selection and improve long-term outcomes for kidney transplants, as 32% of graft failures were linked to donors with two risk variants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The APOL1 gene and allograft survival after kidney transplantation. Reeves-Daniel, AM., DePalma, JA., Bleyer, AJ., et al.[2023]

APOL1 high-risk genotypes significantly increase the risk of chronic kidney disease, particularly in individuals of sub-Saharan African ancestry, highlighting the need for targeted treatment approaches.

Current treatments like hypertension control and immunosuppressive agents are not very effective, but new therapies such as small molecule inhibitors and antisense oligonucleotides show promise and warrant further clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment potential in APOL1-associated nephropathy. Friedman, DJ., Ma, L., Freedman, BI.[2023]

Genetic mutations in the apolipoprotein L1 (ApoL1) gene are linked to a higher risk of kidney disease, particularly in African Americans, where about 39% carry one high-risk allele and 12% carry two, contributing to increased kidney failure rates compared to European Americans.

Kidney grafts from deceased donors with two ApoL1 risk alleles have poorer survival rates, but the recipient's ApoL1 status does not affect outcomes; therefore, it is recommended to counsel living donors of African ancestry about their ApoL1 status to inform decision-making regarding kidney donation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Introducing Genetic Tests With Uncertain Implications in Living Donor Kidney Transplantation: ApoL1 as a Case Study. Ross, LF., Thistlethwaite, JR.[2022]

Genetic variants in the apoL1 gene, which are present only in individuals with recent African ancestry, significantly contribute to higher rates of severe kidney diseases in Black individuals, including hypertension-associated end-stage kidney disease (ESKD) and FSGS.

Understanding the population genetics of APOL1 risk variants is crucial for nephrologists, as it informs the clinical management of patients who may be affected by APOL1 nephropathy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

APOL1 Nephropathy: From Genetics to Clinical Applications. Friedman, DJ., Pollak, MR.[2023]

A significant majority (61%) of African American respondents expressed interest in ApoL1 genetic testing when considering becoming living kidney donors, with factors like age, perceived kidney disease risk, and interest in genetics influencing this interest.

Among those awaiting transplantation, 89% believed ApoL1 testing should be conducted on deceased donors, indicating strong support for genetic testing in the context of kidney transplantation among African Americans.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Opinions of African American adults about the use of apolipoprotein L1 (ApoL1) genetic testing in living kidney donation and transplantation. Berrigan, M., Austrie, J., Fleishman, A., et al.[2023]

References

1. United States pubmed.ncbi.nlm.nih.gov

"Biomarking" the transition from genetic risk to kidney disease. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

Integrating APOL1 Gene Variants Into Renal Transplantation: Considerations Arising From the American Society of Transplantation Expert Conference. [2023]

3. United States pubmed.ncbi.nlm.nih.gov

Variation of ApoL1 Testing Practices for Living Kidney Donors. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

The APOL1 gene and allograft survival after kidney transplantation. [2023]

5. England pubmed.ncbi.nlm.nih.gov

Treatment potential in APOL1-associated nephropathy. [2023]

6. United States pubmed.ncbi.nlm.nih.gov

Introducing Genetic Tests With Uncertain Implications in Living Donor Kidney Transplantation: ApoL1 as a Case Study. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

APOL1 Nephropathy: From Genetics to Clinical Applications. [2023]

8. United States pubmed.ncbi.nlm.nih.gov

Opinions of African American adults about the use of apolipoprotein L1 (ApoL1) genetic testing in living kidney donation and transplantation. [2023]