According to the National Kidney Foundation, Black Americans, who are disproportionately impacted by chronic kidney disease (CKD), are three times more likely to experience kidney failure than their white counterparts. Methods used to diagnose CKD have traditionally underestimated the severity of illness in Black patients, leading to delayed treatments and interventions needed to protect kidney function.
Researchers are working to identify people at risk for kidney disease before symptoms develop, and a recent study published in Nature Medicine used APOL1 genetic testing to help predict that risk.
The study, “Proteomic risk score for early prediction of kidney disease progression in individuals with APOL1 high-risk genotypes,” was led by researchers at the University of Pennsylvania Perelman School of Medicine. Researchers analyzed biological samples from 851 Black participants with the high-risk APOL1 genotypes in the Penn Medicine BioBank (PMBB), a research program focused on genomics and personalized medicine.
Variants in the APOL1 gene are associated with an increased risk of kidney disease, particularly in people of African ancestry. Researchers developed a 9-protein APOL1 Proteomic Risk Score (APRS) as a predictor of future disease to include kidney decline, kidney failure, dialysis, transplant, or death. The APRS score of 86 percent outperformed the current standard, the Kidney Failure Equation (KFE), at 66 percent.
Researchers found that many high-risk individuals had normal kidney labs despite the test identifying them at risk, indicating the disease may progress for years before standard detection. The study supported the personalized-medicine, two-pronged approach: genetics identifies susceptibility, and proteomics identifies those whose disease is actively progressing.
“What has been missing is a way to identify early disease activity before we see changes in standard clinical measures,” said Katalin Susztak, MD, PhD, the senior study author and professor in Renal Electrolyte and Hypertension and director of the Penn/CHOP Kidney Innovation Center, in an article on the Penn Medicine website. “This approach allows us to intervene early enough and lessen the severity, or even prevent, kidney disease in some patients.”
Historically Black patients have often been diagnosed after irreparable kidney damage has occurred. The study suggests that providers may be able to identify high-risk patients sooner. Black patients have higher rates of high blood pressure, obesity, diabetes, and heart disease, all of which can increase the risk of kidney disease. Early detection and regular screening are critical for improving outcomes and preventing disease progression.
While widespread APRS proteomic testing is not standard, clinicians could begin incorporating APOL1 results by offering testing to high-risk individuals to help them qualify for clinical trials, such as the APOL1 drug Inaxaplin, mentioned in the study and currently in Phase 3.
Testing could further help clinicians:
The study suggests that kidney damage may begin before creatinine levels rise. Because many patients with high-risk APOL1 variants still have normal kidney labs, providers may need to begin monitoring kidney function earlier, before eGFR declines become apparent.
In addition, APOL1 testing may improve kidney transplant evaluation and living donor counseling by helping clarify genetic risk. However, this information must be interpreted carefully. APOL1 variants increase risk but do not guarantee disease is present, and misinterpretation could worsen disparities in donor access.
This research highlights how genetic testing can improve risk prediction for kidney disease. But genetics is just one part of the equation. APOL1 variants are associated with a higher risk of CKD and kidney failure for the Black population. The study found that while genomics may help identify patients at risk of progressing to kidney failure, genetic risk itself does not indicate who will develop kidney disease and who will not. This means that it is not a one-size-fits-all interpretation and that other factors play a critical role in determining outcomes.
The proteomic risk score does help identify genetically high-risk individuals who may be experiencing disease progression. The score, however, is not an answer in itself. It should be used as part of a comprehensive approach that bridges clinical and public health by promoting earlier screenings, hypertension management, and access to care. Genomics is an important tool, but it does not replace addressing the factors that drive health disparities in the Black community.
By subscribing, you consent to receive emails from BlackDoctor.pro You may unsubscribe at any time. Privacy Policy & Terms of Service.
Are you a healthcare professional? Register with us today!