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

Urinary Biomarkers for Lupus Nephritis: A Systems Biology Approach

“…Additionally, urinary IL-16 abundance correlated with single-cell RNA sequencing analyses of renal biopsies, indicating that IL-16 is produced by infiltrating immune cells in LN kidneys, supporting its utility as a biomarker for monitoring intrarenal immune activity [49]. In 225 patients with LN, urine proteomic signatures showed that fibrous crescents were similar to activity-related lesions despite being considered inactive lesions [48]. Despite their classification under the NIH chronicity index, an inflammatory signature including CD73, MMP9, MIP1b, and IL-8 was identified in fibrous crescents, highlighting the potential for tailored interventions [50].…”

“…Recent urinary proteomic studies have revealed a consistent elevation in IL-16 in the urine of patients with active LN [48]. IL-16, a potent T-cell chemoattractant, significantly correlates with renal activity and the NIH indices-histopathology-based scoring systems designed to quantify the severity and progression of LN [49].…”

“…IL-16, a potent T-cell chemoattractant, significantly correlates with renal activity and the NIH indices-histopathology-based scoring systems designed to quantify the severity and progression of LN [49]. Moreover, an early decline in urinary IL-16 at 3 months correlated with treatment response to immunosuppression-a response determined based on UPCR, serum creatinine, and the dose of prednisone-outperforming traditional measures like UPCR [48]. In addition to its predictive value for treatment response, IL-16 can distinguish between proliferative LN and pure membranous LN with an AUC of 0.89 [49].…”

“…Beyond IL-16, CD163-a macrophage-specific hemoglobin scavenger receptor upregulated during inflammation-has been consistently identified as a urinary biomarker through ELISA and single-cell transcriptomics techniques in patients with LN [51][52][53]. Urinary CD163, closely following IL-16, significantly correlates with LN severity indicated by the NIH activity index and histological activity [48,54]. Urinary CD163 concentration improved considerably by week 12 in complete treatment responders, with a decline at three months predicting a one-year response more accurately than proteinuria [48].…”

“…Urinary CD163 concentration improved considerably by week 12 in complete treatment responders, with a decline at three months predicting a one-year response more accurately than proteinuria [48]. Elevated CD163 levels across all LN classes, especially in proliferative forms, were closely linked to disease activity and treatment response, highlighting its utility as a non-invasive marker for tracking LN progression and therapeutic efficacy [48].…”