Urine proteomic signatures of histological class, activity, chronicity, and treatment response in lupus nephritis

Abstract

AbstractLupus nephritis (LN) is a pathologically heterogenous autoimmune disease linked to end-stage kidney disease and mortality. Better therapeutic strategies are needed as only 30-40% of patients completely respond to treatment. Noninvasive biomarkers of intrarenal inflammation may guide more precise approaches. Because urine collects the byproducts of kidney inflammation, we studied the urine proteomic profiles of 225 LN patients (573 samples) in the longitudinal Accelerating Medicines Partnership (AMP) in RA/SLE cohort. Urinary biomarkers of monocyte/neutrophil degranulation (i.e., PRTN3, S100A8, azurocidin, catalase, cathepsins, MMP8), macrophage activation (i.e., CD163, CD206, galectin-1), wound healing/matrix degradation (i.e., nidogen-1, decorin), and IL-16 characterized the aggressive proliferative LN classes and significantly correlated with histological activity. A decline of these biomarkers after 3 months of treatment predicted the 1-year response more robustly than proteinuria, the standard of care (AUC: CD206 0.92, EGFR 0.9, CD163 0.89, proteinuria 0.8, p<0.01). Candidate biomarkers were validated and provide new potentially treatable targets. We propose these biomarkers of intrarenal immunological activity as noninvasive tools to diagnose LN, guide treatment, and as surrogate endpoints for clinical trials. These findings provide new insights into the processes involved in LN activity. This dataset (matching other AMP omics) is a public resource to generate and test hypotheses and validate biomarkers.