Beyond the Needle: Redefining the Assessment of Lupus Nephritis Save

Lupus nephritis is one of the most silent and severe manifestations of systemic lupus erythematosus (SLE). When not captured early, patients are at high risk of progressing to end-stage renal disease, which would require dialysis or transplantation. Renal biopsy remains the gold standard for diagnosis and disease classification. However, the procedure is invasive and very painful. Renal biopsy carries risks and patients may opt to not undergo biopsy due to personal preferences. Non-invasive measures are critical for early detection and continuous monitoring.

One promising approach lies in urinary proteomics. Previous work identified urinary protein signatures linked to Class III and IV lupus nephritis through the Accelerating Medicine Partnership. Building on this, Abstract 1686 investigated whether similar protein signatures might be detected in earlier stages, specifically Class II lupus nephritis. The study revealed a comparable profile of proteins associated with immune activation and tissue remodeling. These findings suggest that identifying immune and fibrotic processes early through urinary proteomics could warrant aggressive management and improved outcomes in lupus nephritis.

Further supporting this approach, Abstract 1642, which will be featured in the Plenary session on Sunday, November 17, identified 12 urinary biomarkers that outperformed traditional clinical biomarkers in predicting an NIH activity index greater than 2. These markers also showed a strong correlation with treatment response, evidenced by reversible changes observed in follow-up renal biopsies. Together, these studies underscore the potential of urinary proteomics to refine the detection, monitoring, and management of lupus nephritis."

The Renal Activity Index for Lupus (RAIL) represents another structured approach toward using urinary proteins in the clinical setting. Based on six urinary biomarkers, previous research demonstrated the ability of RAIL to distinguish high vs low lupus nephritis activity. Additionally, the RAIL algorithm successfully predicted treatment response in pediatric and young adult patients with lupus nephritis. Abstract 1685 took this further by determining which patients were likely to achieve complete renal remission (CRR) at the present and subsequent visits following induction therapy. This tool has the potential to offer patients and physicians real-time insights into the underlying activity of the kidney, supporting timely therapeutic adjustments and more personalized care.

In addition to urinary biomarkers, advanced imaging techniques present another frontier in lupus nephritis monitoring. Tubulointerstitial fibrosis (TIF), a marker of poor renal prognosis, is essential to detect early and prevent further disease progression. Abstract 1683 evaluated whether a specialized tracer called fibroblast activation protein inhibitor (FAPI) is associated with TIF on PET imaging. The study showed increased FAPI uptake in lupus nephritis patients compared to controls. The increased uptake correlated with TIF on renal biopsy. Additional molecular analysis revealed an association with specific interferon pathways. While additional research is needed, FAPI PET imaging could offer a novel, non-invasive method to assess and quantify disease activity in lupus nephritis.

In conclusion, while renal biopsy is the cornerstone for lupus nephritis diagnosis and treatment assessment, non-invasive strategies such as urinary biomarkers and PET imaging are promising advancements. With continued studies and rigorous validation, these tools may provide a new window of opportunity into the underlying lupus nephritis.