Effects of Testing and Disclosing Ancestry-Specific Genetic Risk for Kidney Failure on Patients and Health Care Professionals
Authors: Girish N. Nadkarni, Kezhen Fei, Michelle A. Ramos, Diane Hauser, Emilia Bagiella, Stephen B. Ellis, Saskia Sanderson, Stuart A. Scott, Tatiana Sabin, Ebony Madden, Richard Cooper, Martin Pollak, Neil Calman, Erwin P. Bottinger, Carol R. Horowitz
Journal: JAMA Network Open (2022)

<h3>Importance</h3> Risk variants in the apolipoprotein L1 (<i>APOL1</i>[OMIM603743]) gene on chromosome 22 are common in individuals of West African ancestry and confer increased risk of kidney failure for people with African ancestry and hypertension. Whether disclosing<i>APOL1</i>genetic testing results to patients of African ancestry and their clinicians affects blood pressure, kidney disease screening, or patient behaviors is unknown. <h3>Objective</h3> To determine the effects of testing and disclosing<i>APOL1</i>genetic results to patients of African ancestry with hypertension and their clinicians. <h3>Design, Setting, and Participants</h3> This pragmatic randomized clinical trial randomly assigned 2050 adults of African ancestry with hypertension and without existing chronic kidney disease in 2 US health care systems from November 1, 2014, through November 28, 2016; the final date of follow-up was January 16, 2018. Patients were randomly assigned to undergo immediate (intervention) or delayed (waiting list control group)<i>APOL1</i>testing in a 7:1 ratio. Statistical analysis was performed from May 1, 2018, to July 31, 2020. <h3>Interventions</h3> Patients randomly assigned to the intervention group received<i>APOL1</i>genetic testing results from trained staff; their clinicians received results through clinical decision support in electronic health records. Waiting list control patients received the results after their 12-month follow-up visit. <h3>Main Outcomes and Measures</h3> Coprimary outcomes were the change in 3-month systolic blood pressure and 12-month urine kidney disease screening comparing intervention patients with high-risk<i>APOL1</i>genotypes and those with low-risk<i>APOL1</i>genotypes. Secondary outcomes compared these outcomes between intervention group patients with high-risk<i>APOL1</i>genotypes and controls. Exploratory analyses included psychobehavioral factors. <h3>Results</h3> Among 2050 randomly assigned patients (1360 women [66%]; mean [SD] age, 53 [10] years), the baseline mean (SD) systolic blood pressure was significantly higher in patients with high-risk<i>APOL1</i>genotypes vs those with low-risk<i>APOL1</i>genotypes and controls (137 [21] vs 134 [19] vs 133 [19] mm Hg;<i>P</i> = .003 for high-risk vs low-risk<i>APOL1</i>genotypes;<i>P</i> = .001 for high-risk<i>APOL1</i>genotypes vs controls). At 3 months, the mean (SD) change in systolic blood pressure was significantly greater in patients with high-risk<i>APOL1</i>genotypes vs those with low-risk<i>APOL1</i>genotypes (6 [18] vs 3 [18] mm Hg;<i>P</i> = .004) and controls (6 [18] vs 3 [19] mm Hg;<i>P</i> = .01). At 12 months, there was a 12% increase in urine kidney disease testing among patients with high-risk<i>APOL1</i>genotypes (from 39 of 234 [17%] to 68 of 234 [29%]) vs a 6% increase among those with low-risk<i>APOL1</i>genotypes (from 278 of 1561 [18%] to 377 of 1561 [24%];<i>P</i> = .10) and a 7% increase among controls (from 33 of 255 [13%] to 50 of 255 [20%];<i>P</i> = .01). In response to testing, patients with high-risk<i>APOL1</i>genotypes reported more changes in lifestyle (a subjective measure that included better dietary and exercise habits; 129 of 218 [59%] vs 547 of 1468 [37%];<i>P</i> &lt; .001) and increased blood pressure medication use (21 of 218 [10%] vs 68 of 1468 [5%];<i>P</i> = .005) vs those with low-risk<i>APOL1</i>genotypes; 1631 of 1686 (97%) declared they would get tested again. <h3>Conclusions and Relevance</h3> In this randomized clinical trial, disclosing<i>APOL1</i>genetic testing results to patients of African ancestry with hypertension and their clinicians was associated with a greater reduction in systolic blood pressure, increased kidney disease screening, and positive self-reported behavior changes in those with high-risk genotypes. <h3>Trial Registration</h3> ClinicalTrials.gov Identifier:NCT02234063