This study aimed to identify the pathogenic signal pathway and elucidate urinary biomarkers for predicting the presence or severity of histologic findings in lupus nephritis.1
Methods: Urine samples from patients with biopsy-proven active lupus nephritis were screened for 1,305 proteins using an aptamer-based proteomic assay. The diversity and expansion of individual renal histologic features in lupus nephritis were quantified to identify the urinary proteins associated with the histologic 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 localization of the candidate proteins.
Results: Cluster analysis extracted five histologic subgroups according to their correlations with each histologic finding in lupus nephritis. Protein groups that correlated with each histologic subgroup revealed a distinct pathogenesis in lupus nephritis using pathway analyses. Enzyme-linked immunosorbent assay validation revealed that urinary calgranulin B (S100A9), monocyte chemotactic protein 1 (MCP-1), and insulin-like growth factor binding protein 5 (IGFBP-5) levels could specifically predict the presence and severity of active glomerular lesions, interstitial inflammation, and interstitial fibrosis, respectively. Immunohistochemical staining revealed the localization of these proteins in each lesion.
Commentary: “Although this study involved a relatively small sample size, it lays promising groundwork for the conceptualization of a liquid biopsy in [lupus nephritis],” wrote Andrea Fava, MD, Johns Hopkins University, Baltimore, in a commentary in the same issue of Arthritis & Rheumagology.2 “Biomarkers, by definition, provide a more convenient or noninvasive way [than kidney biopsy] to reflect biologic states or predict outcomes. … The framework proposed by this study, with its focus on principal histologic components and their relative biomarkers, might, if validated, refine the current prognostic limitations of renal biopsies by introducing a granular, longitudinal perspective through noninvasive biomarkers.”
Excerpted & Adapted From
- Hiramoto K, Saito S, Hanaoka H, et al. Urinary biomarkers associated with pathogenic pathways reflecting histologic findings in lupus nephritis. Arthritis Rheumatol. 2025 Mar;77(3):298–310.
- Fava A. Urinary biomarkers: Toward a liquid biopsy for lupus nephritis. Arthritis Rheumatol. 2025 Mar;77(3):244–246.
Note: For source material, refer to the full study.
