Renal Inflammation Assessment using Complement Activation and CD163

Abstract

Lupus nephritis (LN) and renal ANCA-associated vasculitis (rAAV) are autoimmune kidney diseases that can lead to kidney failure, cardiovascular complications, and death. Kidney biopsy remains the gold-standard diagnostic, an invasive procedure with risks. Commonly used non-invasive surrogates, including urine protein-creatinine ratios (UPCR), hematuria, and autoantibody levels, lack sensitivity and specificity for active inflammation. Our pilot study evaluated urine-soluble CD163 (usCD163), urine complement activation products (uCAPs: C3a, C5a, sC5b-9), and SIGLEC-1, as candidate non-invasive kidney inflammation biomarkers. Patients with biopsy-proven LN or rAAV were enrolled, and urine samples were collected from -14 days to +238 days relative to biopsy. Biomarker levels were measured using ELISA or MesoScale-Discovery assays. UsCD163 and UPCR were significantly elevated in LN and rAAV versus healthy controls. usCD163 and uCAPs correlated strongly with UPCR, and the biomarker panel distinguished complete renal remission (CRR) from non-remission. Validation in a larger, longitudinal cohort is underway.