Inflammation-based risk score predicts kidney survival in children and adults with chronic kidney disease

Chronic kidney disease (CKD) is accompanied by systemic inflammation, but whether inflammatory proteins improve risk stratification beyond kidney function and albuminuria remains unclear. We profiled baseline serum samples from 683 children with CKD in the prospective European 4C study using the Olink Target 96 Inflammation panel and related protein levels to kidney outcomes over 8 years. eGFR and albuminuria were the dominant determinants of the inflammation-related serum proteome. Nonetheless, a four-protein inflammation score (iScore; CD40, CD137, PD-L1 and CX3CL1), defined from protein residuals independent of eGFR and albuminuria, stratified kidney survival and predicted CKD progression beyond established clinical risk factors (adjusted hazard ratio per elevated protein, 1.11; 95% CI, 1.01-1.22). The score showed concordant associations in 2,770 UK Biobank participants with reduced eGFR (adjusted hazard ratio, 1.08; 95% CI, 1.02-1.14). Kidney single-cell transcriptomic analysis mapped these axes to immune-parenchymal communication programs in CKD, supporting inflammation-based risk stratification across the life course.