Researchers identify possible genetic risk linked to AKI in patients with kidney disease
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Key takeaways:
- Two novel loci reached genome-wide significance in the meta-analysis.
- Genetic correlation shared significant architecture between AKI and eGFR.
Researchers have identified two loci that may be associated to AKI in hospitalized patients with kidney disease, noting a potential genetic risk of the condition, data show.
“Both indirect and direct evidence suggests a genetic basis for AKI,” Edward D. Siew, MD, MSCI, and Jacklyn N. Hellwege, PhD, of Vanderbilt University Medical Center, wrote with colleagues. However, many studies “have examined homogeneous populations, such as patients undergoing surgery. Interpretation has been challenged by smaller sample sizes and limited enrichment for phenotypes likely to reflect parenchymal injury,” the researchers wrote.
In the genome-wide association study conducted via the Million Veteran Program and with data from the Vanderbilt University Medical Center DNA biobank, investigators studied 54,488 patients with AKI and 138,051 without AKI between 2002 and 2019 to determine the relationship between genetic variants and AKI risk in hospitalized patients.
Patients with a modified Kidney Disease: Improving Global Outcomes stage 1 or more for 2 or more consecutive days, or kidney replacement therapy, were held to have AKI. Patients in the control group had one or more qualifying hospitalizations without AKI and had no trace of AKI during any other admissions. Researchers adjusted findings for patients’ race, sex, age, baseline eGFR and ancestry components.
Two novel loci reached genome-wide significance in the meta-analysis, according to the study results: rs11642015, near the FTO locus on chromosome 16, was associated with obesity traits; and rs4859682 near the SHROOM3 locus on chromosome 4, was linked to glomerular filtration barrier integrity. Each colocalized with previous studies, the researchers found, adding that genetic correlation shared much architecture between AKI and eGFR.
In addition, the association at the FTO locus was attenuated after adjusting for BMI and diabetes, which may indicate the relationship is in part driven by obesity.
The findings warrant further study to “delineate the differences between premorbid susceptibility conferred by these candidate variants for AKI and directly conferred risk in the acute setting are warranted,” the researchers wrote.
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