Background We employed urine proteomics to define the molecular signatures associated with the histological features quantified by the NIH activity and chronicity indices.
Methods We employed urine proteomics to define the molecular signatures associated with the histological features quantified by the NIH activity and chronicity indices.
Results Glomerular and interstitial lesions in lupus nephritis were quantified (scored 0–3) based on the revised 2018 International Society of Nephrology/Renal Pathology Society (ISN/RPS) classification for lupus nephritis and the modified NIH scoring system by a central renal pathologist (JH). Urinary proteins (1200 biomarkers, RayBiotech Kiloplex) were quantified in urine samples collected on the day of (73%) or within 3 weeks of (27%) the diagnostic kidney biopsy. Proteomic signatures of each lesion were defined based on Spearman correlations of each urine protein with each pathologic lesion.
Conclusions Ninety-one biopsies were included: 32 (35%) with pure proliferative LN, 33 (36%) with pure membranous LN, and 26 (29%) with mixed LN. The 5 most correlated urinary proteins and each pathologic feature are summarized in Figure 1A-B. Most lesions in the activity or chronicity indices shared a similar signature within their respective index. In contrast, fibrous crescents displayed an inflammatory signature (CD73, MMP9, MIP1b, and IL-8) despite being part of the NIH chronicity index. Hierarchical clustering based on proteomic signatures revealed that fibrous crescents were more similar to activity-related lesions (figure 1c). Interstitial inflammation (activity) was correlated with biomarkers associated with both active and chronic lesions.
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