Trial showed benefits in hypertensive patients of African descent

For hypertensive people of African ancestry, knowing their genetic risk for chronic kidney disease modestly helped with their efforts to prevent it, a pilot randomized clinical trial showed.

Three months after being given the news that they carried high-risk variants in the APOL1 gene on chromosome 22, patients had a significantly greater reduction in systolic blood pressure than those told they had low-risk APOL1 genotypes or who weren’t told their genetic risk (mean 6 vs 3 mm Hg in both other groups).

By 12 months, those with information about their high genetic risk were more likely to have gotten urine albumin testing for kidney disease (an increase of 12 vs 6 to 7 percentage points in the other two groups, P=0.01 vs controls), Girish Nadkarni, MD, MPH, of the Icahn School of Medicine at Mount Sinai in New York City, and colleagues reported in JAMA Network Open.

The patients with high-risk APOL1 genotypes more often reported improving their dietary and exercise habits (59% vs 37% with low-risk genotypes, P<0.001) and increasing their antihypertensive use (10% vs 5%, P=0.005).

The trial returned the genetic results to both the patients in the intervention group and their primary care physicians, conveyed through trained laypersons and alerts in the electronic health record (EHR), respectively.

Thus, the researchers suggested that their results “may support an approach of broad implementation of genetic medicine in primary care.”

Primary care is where most healthcare happens for patients, and although genetic counselors have typically been on the front lines of genetic testing, they are in short supply compared with the number of people who would need it for common conditions.

High-risk variants of APOL1 are found in one of seven people of African ancestry, for whom they confer a five- to 10-fold increased risk for chronic and end-stage kidney disease from hypertension.

Getting such genetic testing into broad use “will benefit racial and ethnic minority groups that have been traditionally underrepresented in both clinical trials and genetic studies,” Nadkarni’s group noted.

The trial used layperson coordinators, mainly of African ancestry, who had been trained by genetic counselors to convey test results and “to be sensitive to the culture and challenges facing patients.” This approach was viewed “very favorably,” with only 3% of patients saying they wouldn’t choose to get tested again.

“Clinician extenders (nurse practitioners and physician assistants) may be useful for other practices to consider to permanently fill this role for busy clinicians or as a bridge while clinicians learn to incorporate information from a relatively new field into their workflow,” the researchers suggested.

The trial enrolled 2,050 patients of African ancestry with hypertension from 15 academic, community, and safety-net practices in two health systems in New York City. Participants were randomly assigned 7:1 to immediately be given APOL1 allele genotype results or for results to be delayed until after the 12-month visit (controls).

The coordinators collected venous blood samples (or saliva samples, if needed) for genetic testing at baseline and then returned the results in person for high-risk APOL1 genotypes (homozygous or compound heterozygous G1 or G2 alleles) or over the phone for patients who were low-risk, heterozygous G1 or G2 or homozygous wild-type allele carriers.

Participants’ primary care physicians got a one-time EHR alert — with the genotype result, recent blood pressure readings, and links to information — when they saw the patient within the 12-month follow-up period.

Few prior studies testing the impact of disclosing genetic risk for chronic diseases have found it improved outcomes, Nadkarni’s group noted. The benefits in this trial, while modest, “may be due to the use of EHR alerts, which have previously shown efficacy, along with disclosure of genetic results to patients.”

“The magnitude of systolic blood pressure improvement was small, but we did not provide specific BP target recommendations or BP-lowering strategies to clinicians or patients,” they noted. It’s possible that more intense BP-lowering efforts would boost the impact.

There were some downsides to disclosure of high-risk genotypes, with more of these patients upset about their results (8% vs 1%, P<0.001) and worried they would develop kidney problems (27% vs 17%, P<0.001).

“We offered all patients the opportunity to speak to or meet with a genetic counselor at no cost; however, none chose to do so,” the researchers noted.

Limitations included exclusion of patients with pre-existing chronic kidney disease and lack of comprehensive data on lifestyle and dietary intake or medication refill data.

A similarly designed 5,400-patient national trial, GUARDD-US, is underway and expected to reach completion at the end of the year.