JAMA Netw Open. 2026 Mar 2;9(3):e260528. doi: 10.1001/jamanetworkopen.2026.0528.
ABSTRACT
IMPORTANCE: Apolipoprotein L1 locus (APOL1) high-risk alleles are associated with incidence of chronic kidney disease (CKD) among people with African ancestry. Few studies have examined the effect of genetic return of results on blood pressure (BP) management and control.
OBJECTIVE: To determine whether providing APOL1 high-risk genotype results to people with hypertension and their clinicians would reduce systolic BP (SBP) and improve CKD screening and diagnosis.
DESIGN, SETTING, AND PARTICIPANTS: From July 1, 2020, to September 30, 2023, adults aged 18 to 70 years with hypertension and self-reported African ancestry were enrolled at 14 institutions and 54 clinical sites across the US. Eligible patients either (1) lacked diagnoses of diabetes and CKD or (2) had a diagnosis of CKD with or without diabetes.
INTERVENTIONS: Participants were randomized to receive APOL1 genotype results immediately (intervention) or 6 months after enrollment (control). Clinical decision support encouraged appropriate CKD screening, diagnosis, and antihypertensive therapy.
MAIN OUTCOMES AND MEASURES: The primary outcome was change in SBP in individuals with APOL1 high-risk allelles at 3 months, assessed in a modified intention-to-treat analysis. Prespecified per-protocol subgroup analyses included those with uncontrolled BP (baseline SBP ≥140 mm Hg or diastolic blood pressure ≥90 mm Hg), uncontrolled BP while receiving antihypertensive therapy, and CKD at enrollment. Secondary outcomes included urine microalbumin screening and new CKD diagnoses.
RESULTS: Of 6754 individuals recruited (mean [SD] age, 55.3 [10.3] years; 4310 women [63.8%]), 954 (14.1%; mean [SD] age, 54.9 [10.0] years; 600 women [62.9%]) had 2 APOL1 risk alleles. At 3 months, there was no difference in SBP between the intervention and control groups (between-group difference, -0.3 mm Hg [95% CI, -2.7 to 2.1 mm Hg]). Among 377 individuals with uncontrolled BP, the mean SBP change was -4.1 mm Hg (95% CI, -7.7 to -0.5 mm Hg) more in the intervention group than the control group (P = .004). SBP improvement was also observed for the intervention in the subgroup of patients with uncontrolled BP receiving antihypertensive therapy (SPB difference, -4.3 mm Hg [95% CI -8.0 to -0.5 mm Hg]; P = .004), but not the CKD subgroup (SPB difference, 0.8 mm Hg [95% CI, -3.0 to 4.5 mm Hg]). Provision of APOL1 genotype led to increased urine microalbumin screening (between-group difference, 17.3% [95% CI, 9.6%-24.9%]; P < .001) and CKD diagnoses (between-group difference, 5.7% [95% CI, 2.2%-9.3%]; P = .002) at 6 months.
CONCLUSIONS AND RELEVANCE: Provision of APOL1 genotype high-risk results to participants and clinicians was not associated with SBP reduction overall. Among the subset of patients with uncontrolled BP, the intervention group had a significant SBP reduction. APOL1 disclosure also increased the rate of CKD screening and diagnosis. Effects of reporting APOL1 genotype merit further investigation among those with uncontrolled BP.
TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04191824.
PMID:41784962 | DOI:10.1001/jamanetworkopen.2026.0528
