APOL1 Genetic Testing for Kidney Disease

Not currently recruiting at 2 trial locations

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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to improve the kidney donation process for African American living donors by using genetic testing to assess the risk of future kidney disease. It focuses on APOL1 gene testing, which identifies higher risks for kidney issues in donors with African ancestry. Participants will either receive the usual care or join a new program featuring APOL1 genetic testing, a chatbot for guidance, and enhanced counseling. The trial seeks individuals who are potential kidney donors identifying as African American or having African ancestry, and who can speak English. The goal is to help donors make informed decisions and reduce uncertainty about donating.

As an unphased trial, this study offers participants the chance to contribute to groundbreaking research that could enhance the safety and effectiveness of kidney donation for African American communities.

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 prior data suggests that APOL1 genetic testing is safe for living donor kidney transplantation?

Research shows that APOL1 genetic testing is generally safe and easy to manage. This test identifies specific gene changes, known as G1 and G2, which can increase the risk of kidney disease in people of African ancestry. These changes are associated with a higher likelihood of developing kidney diseases unrelated to diabetes.

The APOL1 test does not involve medication or medical procedures, so it has no physical side effects. It simply indicates the presence of these risk genes, aiding in informed decisions about kidney donation. However, knowing one's genetic risk might cause emotional stress or worry. Counseling is recommended to help understand and manage these feelings.

Overall, the APOL1 genetic test is a valuable tool for assessing risk and is considered safe for those contemplating kidney donation. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about APOL1 genetic testing for kidney disease because it offers a new approach to understanding and potentially managing the condition. Unlike traditional treatments that focus on managing symptoms or slowing disease progression with medications like ACE inhibitors or ARBs, this genetic testing aims to identify individuals at higher risk due to specific genetic variants. By pinpointing those who might benefit from early intervention, APOL1 testing could lead to more personalized treatment strategies and potentially improve outcomes for patients with kidney disease.

What evidence suggests that this trial's treatments could be effective for kidney disease?

Research has shown that certain genetic traits, known as APOL1 variants, link to a higher risk of kidney disease in people of African ancestry. Studies indicate that individuals with these traits have a greater chance of developing chronic kidney disease that worsens over time. The lifetime risk of kidney disease for those with two APOL1 risk variants is estimated to be at least 15%. In this trial, participants in the intervention arm will undergo the APOL1 genetic test, a personalized tool that identifies people at risk for kidney damage not related to diabetes and faster kidney failure. This test is becoming an important part of evaluating kidney donors, especially among African American populations, to ensure informed decision-making and reduce potential risks. ^{1 2 5 6 7}

Who Is on the Research Team?

Elisa J Gordon

Principal Investigator

Northwestern University

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

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]

Citations

1. sciencedirect.com sciencedirect.com/science/article/pii/S2590059525000986

APOL1 Mediated Kidney Disease: A Review and Look ... High-risk APOL1 genotypes have also been associated with an increased risk of disease progression in other processes, such as lupus nephritis and sickle cell ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4562465/

APOL1 kidney disease risk variants – an evolving landscape We estimate the lifetime risk of kidney disease in APOL1 dual-risk allele individuals to be at least 15%. Experimental evidence suggests a direct role of APOL1 ...

3. kdigo.org kdigo.org/wp-content/uploads/2025/08/KDIGO-2025-APOL1-Kidney-Disease-Conference-Report.pdf

APOL1 kidney disease In people of African ancestry, apolipoprotein L1 gene. (APOL1) variants have been identified as causing increased risk of progressive chronic kidney disease ( ...

4. school.wakehealth.edu school.wakehealth.edu/departments/internal-medicine/nephrology/nephrology-research/apol1-genetic-test

APOL1 Genetic Test | Wake Forest University School of ... The APOL1 test is an inexpensive and convenient personalized genetic test that reports on risk for non-diabetic nephropathy and more rapid failure of ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S0085253825004296

APOL1 kidney disease: conclusions from a ... Figure 1. APOL1 high-risk genotypes increase the risk of many types of kidney disease in individuals of recent African ancestry. High-risk ...

6. kidneymedicinejournal.org kidneymedicinejournal.org/article/S2590-0595(25)00098-6/fulltext

APOL1 Mediated Kidney Disease: A Review and Look ... This mini-review discusses the development of APOL1 risk alleles, clinical implications of a high-risk genotype, and a suggested framework for ...

7. kidney.org kidney.org/kidney-topics/apol1-mediated-kidney-disease-amkd

APOL1-Mediated Kidney Disease (AMKD) Studies have shown a link between APOL1 risk variants and a higher risk for kidney disease. These variants are called G1 and G2. People with two ...