Urinary biomarkers associated with pathogenic pathways reflecting histological findings in lupus nephritis

Objective There is a pressing need to understand the pathogenesis of histological findings and identify the biomarkers for predicting the histological severity in lupus nephritis (LN). This study aimed to identify the pathogenic signal pathway and elucidate urinary biomarkers for predicting the presence or severity of histological findings in LN. Methods Urine samples from patients with biopsy‐proven active LN were screened for 1305 proteins using an aptamer‐based proteomic assay. The diversity and expansion of individual renal histological features in LN were quantified to identify the urinary proteins associated with the histological findings found in each score. Candidate urinary proteins were validated in a validation cohort. Immunohistochemical staining of the renal tissues was performed to clarify the localisation of the candidate proteins. Results Cluster analysis extracted five histological subgroups according to their correlations with each histological finding in LN. Protein groups which correlated with each histological subgroup revealed a distinct pathogenesis in LN using pathway analyses. Enzyme‐linked immunosorbent assay validation revealed that urinary calgranulin B (S100A9), MCP‐1, and IGFBP‐5 levels could specifically predict the presence and severity of active glomerular lesions, interstitial inflammation, and interstitial fibrosis, respectively. Immunohistochemical staining revealed the localisation of these proteins in each lesion. Conclusions Renal histological findings may reflect the different pathogeneses involved in each lesion, and estimating the urinary calgranulin B, MCP‐1, and IGFBP‐5 levels may be useful in predicting the presence and severity of histological findings in LN.