Genetic Testing for APOL1 in Adults With Hypertension: The GUARDD-US Randomized Clinical Trial.

Area of Science:

• Genetics and genomics
• Nephrology
• Cardiology

Background:

• Apolipoprotein L1 (APOL1) high-risk alleles are linked to chronic kidney disease (CKD) in individuals of African ancestry.
• The impact of returning genetic results, specifically APOL1 risk alleles, on blood pressure (BP) management and CKD outcomes remains understudied.

Purpose of the Study:

• To evaluate if disclosing APOL1 high-risk genotype results to hypertensive patients and their clinicians improves systolic blood pressure (SBP) control.
• To assess the effect of APOL1 genetic results on CKD screening and diagnosis rates.

Main Methods:

• A randomized controlled trial involving adults with hypertension and self-reported African ancestry across 54 clinical sites in the US.
• Participants were assigned to receive APOL1 genotype results immediately (intervention) or after 6 months (control), with clinical decision support for CKD screening and BP management.

Main Results:

• No significant difference in SBP reduction was observed between the intervention and control groups overall at 3 months.
• In a subgroup analysis, participants with uncontrolled BP in the intervention group showed a significant SBP reduction compared to the control group.
• Provision of APOL1 genotype results led to a significant increase in urine microalbumin screening and new CKD diagnoses at 6 months.

Conclusions:

• Disclosing APOL1 high-risk genotype results did not universally reduce SBP but demonstrated a benefit in patients with uncontrolled hypertension.
• APOL1 genetic disclosure significantly enhanced CKD screening and diagnostic rates.
• Further investigation into the effects of reporting APOL1 genotype is warranted, particularly for individuals with uncontrolled BP.