APOL1 proteomic risk score predicts kidney disease progression

A nine-protein apolipoprotein L1 (APOL1) Proteomic Risk Score (APRS) enables accurate prediction of kidney disease progression in APOL1 high-risk individuals, according to a study published online April 15 in Nature Medicine.

Chenyu Li, Ph.D., from the University of Pennsylvania in Philadelphia, and colleagues profiled plasma proteomes of 851 Penn Medicine BioBank participants of African ancestry with APOL1 high-risk genotypes and preserved estimated glomerular filtration rate (eGFR). APRS, which predicts a composite outcome of ≥40% eGFR decline, kidney failure, or death, was derived using elastic net Cox regression adjusted for age, sex, eGFR, and albuminuria.

The researchers found that the time-dependent area under the receiver operating characteristic curve (tAUC) was 86.5% with APRS, outperforming the Kidney Failure Risk Equation (66.1%) and polygenic risk scores, which had 10-year event rates of 62.5 versus 3.3% across quintiles of risk. Robust accuracy was confirmed in external validation in the Atherosclerosis Risk in Communities and U.K. Biobank cohorts (tAUC, 82% to 85%); performance was consistent across demographic and clinical subgroups. There was a correlation for plasma levels of APRS component proteins with kidney tissue fibrosis and tubular injury pathways.

“One of the challenges in developing new therapies has been identifying the right patients early enough,” senior author Katalin Susztak, M.D., Ph.D., also from the University of Pennsylvania, said in a statement. “This provides a way to focus treatment on those most likely to benefit.”

Several authors disclosed ties to the biopharmaceutical industry.

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