Breakthrough blood test predicts kidney failure years before clinical symptoms

A new blood test can identify which individuals of African ancestry carrying high-risk APOL1 gene variants are most likely to develop kidney failure, years before clinical disease becomes apparent. Findings on the new test, developed by a team from the Perelman School of Medicine at the University of Pennsylvania, are published today in Nature Medicine.

What has been missing is a way to identify early disease activity before we see changes in standard clinical measures. This approach allows us to intervene early enough and lessen the severity, or even prevent, kidney disease in some patients."

Katalin Susztak, MD, PhD, senior author, professor in Renal Electrolyte and Hypertension and director of the Penn/CHOP Kidney Innovation Center

African Americans develop kidney failure at nearly four times the rate of those of European ancestry, driven in part by variants in the APOL1 gene. The APOL1 gene helps protect against certain infections, but some versions of it can also increase the risk of serious kidney disease. An estimated 4 to 5 million people in the United States carry these high-risk variants. However, most will never develop kidney disease, and until now there has been no reliable way to determine who is truly at risk before kidney function begins to decline.

Substantial findings after analyzing blood samples

Researchers analyzed blood samples from more than 850 people of African ancestry enrolled in the Penn Medicine BioBank, all of whom carried APOL1 high-risk variants and had normal kidney function at the start of the study. Using a small panel of circulating proteins measured from a routine blood draw, the team developed a risk score that predicts the likelihood of kidney failure, significant decline in kidney function, or death over the following ten years.

The differences between groups were substantial. More than 60 percent of individuals in the highest-risk category experienced renal failure requiring the need for dialysis or transplantation within ten years, compared to fewer than 1 percent in the lowest-risk group.

The proteins included in the score are linked to pathways involved in kidney injury and fibrosis, suggesting that the test captures early biological changes that precede measurable loss of kidney function.

Two samples show similar results

The findings were validated in two independent cohorts in the United States and the United Kingdom. Across all populations studied, the risk score consistently outperformed existing clinical prediction tools.

The work is aligned with a growing body of research demonstrating that circulating protein markers can reflect underlying tissue-level injury and disease progression. Together, these approaches are helping to move risk assessment in kidney disease beyond traditional clinical measures toward more direct readouts of disease biology.

Researchers say the test could be incorporated into routine care to guide monitoring and treatment decisions, particularly as therapies targeting APOL1-associated disease continue to advance. Several such therapies are currently in development, like experimental drugs designed to block the harmful effects of high‑risk APOL1 variants in the kidney, with the goal of slowing or preventing kidney damage.

"One of the challenges in developing new therapies has been identifying the right patients early enough," Susztak said. "This provides a way to focus treatment on those most likely to benefit."

The team is now working toward bringing the test into the clinic and evaluating how patients' score could support both individual patient care and the design of future clinical trials.

The study was funded by the National Institute of Diabetes and Digestive and Kidney Diseases (DK076077, R01 DK087635 and R01 DK105821), and the National Heart, Lung, and Blood Institute (75N92022D00001, 75N92022D00002, 75N92022D00003, 75N92022D00004 and 75N92022D0000).