Nat Med
Blood test flags kidney failure risk years before function drops
Clinical takeaway: A proteomic blood test may help identify which high-risk APOL1 carriers need closer follow-up or future targeted therapy before chronic kidney disease becomes clinically apparent.
High-risk APOL1 genetic variants are a major driver of kidney failure in people of African ancestry, but most carriers never develop disease. This study tested whether a blood-based protein panel could identify who is most likely to progress before estimated glomerular filtration (eGFR) rate begins to fall.
Investigators developed the nine-protein APOL1 Proteomic Risk Score in 851 people of African ancestry with high-risk APOL1 genotypes and preserved kidney function, then validated it in 296 similar participants in Atherosclerosis Risk in Communities and 195 in UK Biobank.
Over 10 years, the composite outcome of at least 40% eGFR decline, kidney failure, or death occurred in 62.5% of people in the highest-risk quintile vs. 3.3% in the lowest-risk quintile. The score outperformed the Kidney Failure Risk Equation in the target group with normal kidney function, with a time-dependent area under the curve of 86.5% vs. 66.2%, and held up in external validation cohorts, where discrimination remained in the low 80% range.
The component proteins also tracked with fibrosis and tubular injury pathways, supporting the idea that this score may capture early biologic kidney damage before routine clinical measures change.
“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, professor of Renal Electrolyte and Hypertension and director of the Penn/CHOP Kidney Innovation Center at the Perelman School of Medicine, University of Pennsylvania. “This approach allows us to intervene early enough and lessen the severity, or even prevent, kidney disease in some patients.”
Next steps include prospective real-world validation, testing the score as a way to enrich APOL1-targeted clinical trials, and converting the current proteomic platform into a simpler high-throughput clinical assay for broader routine use.
Source: Li C. Nature Medicine. 2026 April 15. Proteomic risk score for early prediction of kidney disease progression in individuals with APOL1 high-risk genotypes